268 results on '"Califf, R.M."'
Search Results
2. Creatine kinase-MB elevation after percutaneous coronary intervention predicts adverse outcomes in patients with acute coronary syndromes
- Author
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Roe, M.T., Mahaffey, K.W., Kilaru, R., Alexander, J.H., Akkerhuis, K.M., Simoons, M.L., Harrington, R.A., Tardiff, B.E., Granger, C.B., Ohman, E.M., Moliterno, D.J., Lincoff, A.M., Armstrong, P.W., Van de Werf, F., Califf, R.M., and Topol, E.J.
- Published
- 2004
3. Management and outcome of patients with atrial fibrillation during acute myocardial infarction: the GUSTO-III experience. (Cardiovascular Medicine)
- Author
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Wong, C-K, White, H.D., Wilcox, R.G., Criger, D.A., Califf, R.M., Topol, E.J., and Ohman, E.M.
- Subjects
Atrial fibrillation -- Drug therapy -- Statistics -- Care and treatment ,Anti-arrhythmia drugs -- Usage -- Statistics ,Cardiac patients -- Drug therapy -- Care and treatment ,Health ,Drug therapy ,Statistics ,Care and treatment ,Usage - Abstract
Objective: To investigate the use of antiarrhythmic agents and electrical cardioversion in the management of patients with atrial fibrillation complicating acute myocardial infarction, and their relation to 30 day and [...]
- Published
- 2002
4. Lack of progress in cardiogenic shock: lessons from the GUSTO trials
- Author
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Menon, V., Hochman, J.S., Stebbins, A., Pfisterer, M., Col, J., Anderson, R.D., Hasdai, D., Holmes, D.R., Bates, E.R., Topol, E.J., Califf, R.M., Ohman, E.M., Menon, V., Hochman, J.S., Stebbins, A., Pfisterer, M., Col, J., Anderson, R.D., Hasdai, D., Holmes, D.R., Bates, E.R., Topol, E.J., Califf, R.M., and Ohman, E.M.
- Abstract
Aims We used the GUSTO-I and GUSTO-III databases to evaluate our performance in treating cardiogenic shock patients over much of the 1990s. Methods and Results GUSTO-I (1990-1993) and GUSTO-III (1995-1997) prospectively identified all patients with cardiogenic shock complicating acute myocardial infarction. Demographics, clinical presentation and outcomes for cardiogenic shock patients in the two trials were compared. Only patients enrolled with cardiogenic shock in countries common to both trials were included in these analysis. The 695 patients with cardiogenic shock in GUSTO-III were compared with the 2814 patients with cardiogenic shock in GUSTO-I. GUSTO-III patients were older (P=0·0001) and more likely to be diabetic (P=0·009) and hypertensive (P=0·025). They had a higher Killip class (P=0·002) and significantly greater index anterior infarction than cardiogenic shock patients enrolled in GUSTO-I. Time to treatment, presentation heart rate, and diastolic blood pressure were similar; however, systolic blood pressure at presentation was higher among GUSTO-III patients (P=0·002). Rates of coronary angiography, pulmonary artery catheterization, and mechanical ventilation declined in GUSTO-III compared with GUSTO-I (P=0·001); rates of angioplasty and bypass surgery were similar. Cardiogenic shock mortality in GUSTO-III was significantly higher than in GUSTO-I (62 vs 54%,P =0·001), as were rates of reinfarction (14 vs 11%, P=0·013) and recurrent ischaemia (35 vs 27%, P=0·00001). Mortality at non-U.S. sites (68 and 64%) was higher than at U.S. sites (53 and 50%) in both GUSTO-I and GUSTO-III studies, respectively. Angioplasty, bypass surgery, and balloon pump rates were lower for non-U.S. patients. Conclusions Cardiogenic shock continues to be associated with high mortality in thrombolytic-treated patients. Lower mortality observed in the U.S.A. supports consideration for percutaneous and surgical revascularization
- Published
- 2017
5. P3622Timing of trial stoppage for non-inferiority trials and interpretation: lessons from ROCKET AF
- Author
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Patel, M., primary, Hellkamp, A.S., additional, Mahaffey, K.W., additional, Singer, D.E., additional, Hacke, W., additional, Breithardt, G., additional, Halperin, J.L., additional, Hankey, G.J., additional, Piccini, J.P., additional, Becker, R.C., additional, Nessel, C.C., additional, Berkowitz, S.D., additional, Fox, K.A.A., additional, and Califf, R.M., additional
- Published
- 2017
- Full Text
- View/download PDF
6. Single bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 randomised trial
- Author
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Werf, F. van de, Adgey, J., Ardissino, D., Armstrong, P.W., Ayleard, P., Barbash, G., Betriu, A., Benbrik, A.S., Califf, R.M., Fanebust, R, Fox, K., Granger, C., Heikkilä, J., Husted, S., Jansky, P., Langer, A., Lupi, E., Maseri, A., Meyer, J., Mlczoch, J., Mocceti, D., Mybirgh, D., Oto, A., Paolasso, E., Pehrsson, K., Seabra-Gomes, R., Soares Pegas, L., Sugrue, D., Tendera, M., Topol, E., Toutouzas, P., Vahanian, A., Verheugt, F.W.A., Wallentin, L., and White, H.
- Subjects
Heartfunction and circulation ,Hartfunctie en circulatie - Abstract
Item does not contain fulltext
- Published
- 1999
7. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes.
- Author
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IMPROVE-IT Investigators, Musliner, T., Tershakovec, A., Gurfinkel, E., Aylward, P., Tonkin, A., Maurer, G., Van de Werf, F., Nicolau, J.C., Theroux, P., Genest, J., Armstrong, P., Corbalan, R., Isaza, D., Spinar, J., Grande, P., Voitk, J., Kesaniemi, A., Bassand, J.P., Farnier, M., Darius, H., Keltai, M., Mathur, A., Mittal, S., Reddy, K., Lewis, B., De Ferrari, G.M., Ophuis, T.O., Jukema, J., White, H., Pedersen, T., Britto, F., Ruzyllo, W., Carrageta, M., Duris, T., Dalby, A., Seung, K.B., Lopez-Sendon, J., Dellborg, M., Mach, F., Guneri, S., Parkhomenko, A., Brady, A., Cannon, C., Blazing, M., Ballantyne, C., de Lemos, J., Kleiman, N., McGuire, D.K., Centeno, E., Casalins, M., Cartasegna, L., Beltrano, M.C., Guerrero, R., Fanuele, M., Berra, F., Egido, J., Colombo, H., Dellatorre, M., Terns, P., Blumberg, E., Reges, P., Azize, G., Ramos, H., Fernandez, R., Carlessi, C., Milesi, R., Schmuck, R., Duronto, E., Procopio, G., Carlevaro, O., Maffeo, H., Beloscar, J., Viso, M., Hominal, M., Castoldi, M., Bluguermann, J., Mauro, D., Macin, S., Cocco, N., Ruiz, N., Ricart, J., Lozada, A., Nani, S., Turri, D., Fernandez, H., Caruso, O., Zarandon, R., Bono, J., Arias, V., Allall, O., Marino, J., Cusimano, S., Schygiel, P., Buzetti, C., Penaloza, N., Berli, M., Worthley, S., Roach, A., Chew, D., Wright, T., Leitch, J., Hicks, E., Rankin, J., Venn-Edmonds, C., Lehman, R., Morrison, H., Shaw, J., Mak, V., Hii, C., Smith, K., Cross, D., Lilwall, L., Nelson, G., Loxton, A., Horowitz, J., Rose, J., Steinwender, C., Leisch, F., Kammler, J., Brussee, H., Zweiker, R., Niederl, E., Weihs, W., Giorgio, G., Lang, I., Drexel, H., Zanolin, D., Hoppe, U., Atzenhofer-Baumgartner, K., Pichler, M., Hainzer, D., Eber, B., Pichler, F., Foeger, B., Wechselberger, T., Mayr, H., Hofer, J., Stockenhuber, F., Warlits, B., Huber, K., Egger, F., Weidinger, F., Ziegler, B., Jirak, P., Metzler, B., Pachinger, O., Wanitschek, M., Auer, J., Grabscheit, G., Podczeck-Schweighofer, A., Priesnitz, T., Frank, H., El Allaf, D., Marechal, P., Roosen, J., Joly, E., Lefebvre, P., Arend, C., Sinnaeve, P., De Velder, L., Hellemans, S., Vanhauwaert, B., Van Dorpe, A., Heyse, A., Vantomme, C., Striekwold, H., Van Den Broeck, D., Lancellotti, P., Schoors, D., Lemoine, I., Taeymans, Y., De Wolf, L., Brike, C., Vercauteren, S., Tahon, S., Vervoort, G., Mestdagh, I., Pirenne, B., Cardinal, F., Lips, S., Dujardin, K., Debrouwer, K., Dhooghe, G., Holvoet, G., van de Borne, P., Renard, M., De Clippel, M., Lesseliers, H., Van Miert, N., Saraiva, J., Vicente, C., Rossi, P., Dos Santos, L.B., Duda, N., Tognon, A.P., Serrano, C., Gomes, F.L., Manenti, E.R., Silveira, D.S., Maia, L., Mouco, O.M., Paiva, M., Antonangelo, A., de Souza, J., Lino, E.A., Leães, P., Blacher, M.G., Kormann, A., Ultramari, F.T., Dutra, O., Mendelski, A.M., Morgado, S., Ardito, W., Greque, G., Ardito, R.V., Pimentel Filho, P., Zucchetti, C., Alves, A., Seabra, A.M., Mattos, M., Miranda, L.F., Silva, D., Uehara, R.M., Marin Neto, J., Schmidt, A., Braga, J., Rodrigues, A., Abrantes, J., Pinheiro, L., Bodanese, L., Magedanz, É.H., Piegas, L., Dos Santos, E.S., Wainstein, M., Ribeiro, J., Stein, R., Marino, R., Machado, V.M., Moraes Junior, J., Guimarães, S., da Costa, F.A., Ferraz, R.F., Albuquerque, D., Rocha, R.M., de Carvalho Moreira, R., Dohmann, H., Costantini, C., Tarastchuk, J.C., Coelho, O., Cirillo, W., Sousa, A., Almeira, A.S., Stefanini, E., Silva, F., Teixeira, M., da Cunha, C., Précoma, D., Facchi, T.L., Rupka, D., Thiessen, S., Warnica, J., Smith, B., Della Siega, A., Klinke, P., Nelson, S., Dion, D., Gilbert, N., Hui, W., Kvill, L., Sussex, B., Luther, A., Dupuis, R., Ouimet, F., Pandey, A., Clarus, S., Senaratne, M., Ferdinandis, H., Mukherjee, A., Bozek, B., Vizel, S., Markov, G., Zimmermann, R., Stephens, W., Tremblay, B., Wong, G., Uchida, N., Brossoit, R., Peck, C., Van Kieu, C., Forgione, M., Bata, I., Cossett, J., Kostuk, W., Arnold, M., Bone, C., Grondin, F., Bilodeau, N., Gosselin, G., David, M., Giannoccaro, J., Beresford, P., Polasek, P., Roberts, P., Doucet, M., Beaudry, M., Cheung, S., Cleveland, T., Bhargava, R., McCallum, A., Ma, P., Morrissette, J., Cleveland, D., Chadwyn, D., Nigro, F., Weeks, A., Cryderman, C., Leader, R., Houde, G., Rousseau, S., Pearce, M., Radyk, M., Lonn, E., Magi, A., Lefkowitz, C., Sandrin, F., Coffin, N., Lubelsky, B., Coldwell, J., Habot, J., McPherson, C., De Larochelliere, R., Roy, M., Haichin, R., Barber, C., Bhesania, T., Kitagawa, H., To, T., Donnelly, B., Tymchak, W., Harris, L., Kouz, S., Huynh, T., St Jacques, B., Lamy, A., Rizzo, A., Stein, J., Childs, C., Wong, B., Poirier, R., Gupta, M., Dela Cruz, C., Constance, C., Gauthier, M., Ervin, F., Ouellette, M., Kokis, A., Lemay, C., Kwok, K., Leung, C., Lee, D., Nesmith, J., Renton, J., Syan, G., Turek, M., Hogan, D., Griffin, P., Lipson, A., Winestock, J., Abramson, B., Fogel, A., Gagne, C., Bergeron, J., Clarke, A., Slipp, S., Darcel, I., Carling-Chambers, L., Kannampuzha, P., Pallie, S., Krekorian, S., Vertes, G., Roth, S., Lai, K., Heath, J., Perez, L., Arriagada, G., Castro, P., Villa, F., Rodríguez, M., Ramos, G., Baraona, F., Núñez, A., García, M., Jofre, C., Silva, P., Lamich, R., Yovaniniz, P., Escobar, E., Dussaubat, A., Segura, E., Ramirez, M., Lapostol, C., Palma, A., Encina, L., Zapata, M., Baeza, N., Varela, P., Pérez, L., Jaramillo, C., Ruiz, S., Sanchez, G., Perdomo, I., Manzur, F., Cohen, L.E., Velasquez, J., Arana, C., Alvarez, Y., Triana, M., Balaguera, J., de Salazar, D., Rendon, N., Botero, R., Ruiz, A., Saaibi, J., Medina, J., Jaramillo, M., Calderón, M.J., Delgado, J., Bohorquez, R., Medina, M.F., Herrera, M., Rosales, D., Mendoza, F., Martinez, S., Ternera, A., Castro, R., Baiz, A., Martinez, M., Orozco, A., Suarez, M., Fonseca, Y., Beltran, R., Cepeda, M., Jaramillo, N., Valenzuela, C., Gutierrez, M., Sanchez, A., Vitovec, J., Hlinomaz, O., Poloczek, M., Mayer, O., Veselka, J., Vejvoda, J., Soucek, M., Spac, J., Novobilsky, K., Srp, V., Francek, L., Branny, M., Sknouril, L., Motovska, Z., Rohac, F., Stankova, A., Fiala, T., Holub, M., Zeman, K., Pohludkova, L., Pospisilova, E., Tuma, P., Cihalik, C., Oral, I., Podpera, I., Stepanovova, R., Uricar, M., Solar, M., Pelouch, R., Porzer, M., Grussmannova, K., Stipal, R., Reichert, P., Hradec, J., Kral, J., Sejkova, B., Janek, B., Pitha, J., Linhart, A., Polacek, P., Koeber, L., Clemmensen, P., Hebin, C.H., Schmidt, E., Pedersen, M.S., Roseva-Nielsen, N., Kristensen, K., Bang-Hansen, T., Jensen, J., Laage-Petersen, J., Nielsen, H., Stokholm, E., Thayssen, P., Cappelen, H., Jensen, T., Winther-Friis, B., Klausen, I., Hedegaard, B., May, O., Andersen, M., Bottzauw, J., Lush, A., Markenvard, J., Vestager, K.M., Bronnum-Schou, J., Hempel, H., Petersen, J., Nielsen, A.J., Thomsen, K., Nielsen, T., Nygaard, A., Sykulski, R., Jensen, B.S., Ralfkiaer, N., Gottschalck, H., Rasmussen, S., Pedersen, L.R., Dodt, K., Skovsbøl, M., Andersen, O., Tuxen, C., Meier, A.W., Kristensen, T., Rasmussen, O., Lopez, J., Salazar, D., Sanchez, L., Rosero, F., Penaherrera, E., Duarte, Y.C., Marmol, R., Andrade, G., Guzman, E., Morillo, A., Aug, L., Loogna, I., Laanmets, P., Mustonen, J., Mäntylä, P., Kesäniemi, A., Ukkola, O., Kervinen, H., Juhela, S., Juvonen, J., Toppinen, A., Jarvenpaa, J., Syvanne, M., Svahn, T., Voutilainen, S., Huotari, A., Nikkila, M., Raiskinmäki, S., Kotila, M., Rajala, A., Laukkanen, J., Hiltunen, P., Melin, J., Nyman, K., Luukkonen, J., Kosonen, P., Huttunen, M., Seppänen, V., Airaksinen, J., Juonala, M., Lehto, S., Savolainen, K., Halkosaari, M., Sia, J., Palomaki, A., Luoma, J., Utriainen, S., Valpas, S., Tiensuu, T., Lilleberg, J., Kainulainen, R., Schiele, F., Bassand, J., Meneveau, N., Galinier, M., Jean, M., Martelet, M., Mouallem, J., Elbaz, M., Puel, J., Carrié, D., Coisne, D., Varroud-Vial, N., Jaboureck, O., Dujardin, J., Leroy, F., Mansourati, J., Funck, F., Jourdain, P., Guillard, N., Coviaux, F., Gay, A., Dourmap-Collas, C., Froger-Bompas, C., Paillard, F., Tricot, O., Maquin-Mavier, I., Dubois-Rande, J.L., Pongas, D., Paris, A.P., Delahaye, F., Ovize, M., Benyahya, L., Bonnet, J., Belle, L., Mangin, L., Lafitte, B., Zemour, G., Doux, N., Agraou, B., El Mansour, N., Traisnel, G., El Jarroudi, M., Ohlmann, P., Diadema, B., Escande, M., Legros, G., Demarcq, J.M., Haftel, Y., Alsagheer, S., Dambrine, P., Cottin, Y., Ghostine, S., Caussin, C., Gacem, A., Bouvier, J.M., Poulard, J., Davy, J., Furber, A., Prunier, F., Muenzel, T., Genth-Zotz, S., Appel, K., Kretzschmar, D., Ferrari, M., Terres, W., Uher, T., Schulze, H., Ochs, H., Morbach, S., Duengen, H., Gross, M., Oezcelik, C., Tahirovic, E., Heuer, H., Laschewski, B., Kadel, C., Rahn, G., Steiner, S., Kreuzer, J., Tsoy, I., Zeiher, A., Muegge, A., Hanefeld, C., Boehm, S., Boudriot, E., Hodenberg, E., Lippe, B., Hausdorf, C., Sydow, K., Baldus, S., Schlesner, C., Tiroch, K., Haltern, G., Guelker, H., Wilhelm, J., Dietz, S., Ebelt, H., Buerke, M., Rupprecht, H., Rittgen, J., Schaeufele, T., Meinhardt, G., Schieber, M., Honold, M., Sieprath, S., Nienaber, C., Hacker, J., Butter, C., Lapp, H., Hirn, S., Pauschinger, M., Zahn, R., Scheffler, U., Schaefer, A., Schieffer, B., Tebbe, U., Kriete, M., Mudra, H., Raeder, T., Braun, P., Zeymer, U., Kouraki, K., Reppel, M., Schunkert, H., Weil, J., Olbrich, H., Schwaiger, P., Mueller, O., Blessing, E., Buss, I., Bohlscheid, V., Kaddatz, J., Skowasch, D., Nickenig, G., Twelker, K., Osterhues, H., Varghese, T., Burghard, S., Kaeaeb, S., Klauss, V., Sohn, H.Y., Hauptmann, K., Schulze, M., Gall, K., Felix, S., Doerr, M., Mante, J., Gulba, D., Freick, M., Werner, G., Kleinertz, K., Hobbach, H.P., Halbach, M., Mueller-Ehmsen, J., Mueller, M.E., Mitrovic, V., Peil, A., Laufs, U., vom Dahl, J., Baumanns, S., Scholtz, W., Wiemer, M., Haude, M., Van de Loo, A., Pistorius, K., Schaefer, J., Schwinger, R., Goeing, O., Jung, W., Birkemeyer, R., Lee, W., Kong, S., Yu, C., Chui, K., Merkely, B., Szelényi, Z., Polgár, P., Svab, S., Herczeg, B., Bajcsi, É., Vértes, A., Davidovits, S., Nagy, A., Király, C., Lupkovics, G., Kenéz, A., Poór, F., Takács, J., Kirschner, R., Simonyi, G., Koncz, J., Édes, I., Gergely, S., Katona, A., Nagy, E., Kovács, Z., Gyetvai, I., Salamon, C., Kolman, É., Sitkei, É., Csapó, K., Molnar, K., Mező, I., Sereg, M., Reddy, P., Manjunath, C., Narayanappa, S., Kumar, S., Sinha, N., Kapoor, A., Christopher, J., Reddy, G., Rani, M., Oomman, A., Ramamurthee, K., Kumar, N., Pasha, S.S., Rao, C., Murty, G.S., Chopra, A., Kapila, D., Bali, H., Chattree, K., Hasan, O., Suryaprakash, G., Rao, D., Babu, R., Bhargavi, M., Naik, S., Khan, S., Chopra, V., Sapra, R., Kaul, U., Ghose, T., Menon, R., Battikadi, S., Mullasari, A., Subban, V.K., Dani, S., Iby, M., Chandra, P., Sethi, S., Bhargava, M., Arora, P., Tyagi, G., Padmanabhan, T., Malhotra, S., Talwar, K., Shafiq, N., Kasliwal, R., Bansal, M., Eldar, M., Berger, M., Shechter, M., Atar, S., Roguin, N., Kilimnik, M., Hayek, T., Hamoud, S., Katz, A., Plaev, T., Shotan, A., Vazan, A., Weiss, A., Leibowitz, D., Zimlichman, R., Ben-Aharon, J., Hammerman, H., Dragu, R., Rozenman, Y., Witzling, V., Tzivoni, D., Moriel, M., Halkin, A., Sheps, D., Bogomolny, N., Mosseri, M., Khudyak, Y., Halabi, S., Uziel-Iunger, K., Yuval, R., Shimoni, S., Caspi, A., Botwin, S., Gavish, D., Sandler, A., Pollak, A., Kreisberg, B., Hussein, O., Jabal, K., Henkin, Y., Grosbard, A., Rosenschein, U., Rivlin, E., Zeltser, D., Platner, N., Porter, A., Harel, N., Lishner, M., Elis, A., Karny, M., Fuchs, S., Stein, G., Grossman, E., Gealel, Z., Schlaeffer, F., Liberty, I., Golik, A., Tzuman, O., De Ferrari, G., Pavesi, C., Poggio, L., Damiano, S., Pazzano, A.S., Mennuni, M., Paloscia, L., Mascellanti, M., Piovaccari, G., Grosseto, D., Mascia, F., Vetrano, A., Zingarelli, A., Mazzantini, S., Visconti, L., Terzi, G., Senni, M., Gavazzi, A., Scuri, P., Carmelo, M., De Caterina, R., Conti, M., Novo, S., Graceffa, A., Arvigo, L., 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Ieva, R., Fattore, L., Cicia, G., Cavallini, C., Tamburino, C., Sacco, A., Mafrici, A., Di Pasquale, G., Pavesi, P.C., Scioli, R., Lioy, E., Occhiuzzi, E., Matino, M.G., Russo, V., Moscogiuri, M.G., Cuccia, C., Forgione, C., Volpe, M., Palano, F., Branca, G., Rossi, R., Modena, M., Olaru, I.A., Zanini, R., Cianflone, D., Cristell, N., Pantaleoni, M., Guiducci, U., Menozzi, C., Gaddi, O., Fasulo, A., Indolfi, C., Emanuele, V., Guerra, F., Iliceto, S., Marotta, C., Morocutti, G., Presbitero, P., Rossi, M., Bonatti, S., Grieco, A., Chiodi, L., Betti, I., Zuppiroli, A., Fanelli, R., Stanco, G., Azzolini, P., Ruggieri, C., Bocconcelli, P., Airoldi, F., Tavano, D., Brunelli, C., Caso, P., Scalzone, A., Ghigliotti, G., Facciorusso, A., Sim, K., Kiam, O., Chee, K., Bin Ismail, O., Zambahari, R., Ophuis, T., van Nes, E., Werter, C.J., Ophuis, A.J., Troquay, R.P., Hamer, B.J., Lenderink, T., Feld, R.J., van Hessen, M.W., Viergever, E.P., van der Sluis, A., Lok, D.J., Badings, E.A., Nierop, P.R., Danse, I.Y., Hermans, W.R., Holwerda, N.J., Thijssen, H.J., Theunissen, L.J., van der Zwaan, C., Van Den Berg, B.J., Hendriks, I.H., Ronner, E., Withagen, A.J., Dijkshoorn-Giesen, A.H., Ezechiels, J.P., Kuijper, A.F., Den Hartog, F.R., Van Kalmthout, P.M., Buijs, E.M., van der Zeijst, M., Zwart, P.A., Zuidgeest, J.A., van Eck, M., Daniels, M.C., van der Ven-Elzebroek, N., Van 't Hof, A., van Boven, A.J., van der Weerdt, A., Dunselman, P.H., Alings, M.A., van Es, R.F., The, S.H., Gurlek, C., Liem, A.H., van Lennep, H.W., Van Vlies, B., Kalkman, C., Swart, H.P., van der Bij, P., Taverne, R., Ciampricotti, R., van Dam, C., Spierenburg, H., van Ruijven, I., van Kempen, L.H., Willems, F.F., Dirkali, A., Stoel, I., Plomp, J., Veldmeijer, S., Tjeerdsma, G., Nijmeijer, R., Van Hal, J.M., Bartels, G.L., Posma, J.L., Linssen, G.C., Fauser, C.G., Waalewijn, R.A., Groenemeijer, B.E., Pos, L., Fast, J.H., Droste, H.T., Westenburg, J., Veenstra, W., Koolen, J., van Loo, L.W., Smits, W., Milhous, J.G., van Rossum, P., Stuij, S., Scott, R., Richards, A.M., Morrison, Z., Devlin, G., Fisher, R., Stewart, R., Benetar, J., Voss, J., Wong, S., Scott, D., Luke, R., Tang, E., Davidson, L., Hamer, A., Wilson, S., Price, R., Hart, H., Turner, A., Jortveit, J., Calic, S., Gundersen, T., Brunvand, H., Fosse, L., Nygaard, O., Gjellefall, B., Gravdal, S.A., Ringstad, R., Atar, D., Clausen, H., Hysing, J., Arvesen, K., Topper, M., Flagstad, E., Graven, T., Haug, H.H., Dalin, L., Al-Ani, R., Otterstad, J., Ausen, K., Aaser, E., Olufsen, M., Halvorsen, S., Gullestad, L., Stueflotten, W., Waage, K., Stødle, R.M., Hall, C., Aase, O., Nordeng, J., Soyland, E., Fageraas, E.R., Lied, A., Aske, R., Raouf, N., Johansson, J., Herrscher, T., Skogrand, E., Bjornstad, H., Aagnes, I., Arntsen, B.I., Vegsundvaag, J., Skjold, M.E., Velle, H., Aambakk, M.B., Skjetne, O., Byfuglien, A., Rodriguez, J., Galvez, D., Medina, F., Hernandez, H.A., Chavez, V., Morales, R., Huapalla, E., Velasquez, D., Torres, F., Aguirre, O., Yanez, L., Andrade, M., Campos, C., Arce, R., Mogrovejo, W., Osores, F., Bustamante, G., Rodriguez, M., Berrospi, P., Garcia, C., Talledo, M., Navarro, P., Horna, M., Herrera, V., Kadziela, J., Rybicka-Musialik, A., Trusz-Gluza, M., Berger-Kucza, A., Musial, W., Tycinska, A., Gil, R., Gziut, A., Gorny, J., Tyllo, M., Reszka, Z., Mickiewicz-Pawlowska, M., Wrzosek, B., Kosior, J., Staneta, P., Korzeniak, R., Kalarus, Z., Markowicz, E., Miekus, P., Konarzewski, M., Kleinrok, A., Puzniak, M., Grajek, S., Janus, M., Krzyzanowski, M., Hoffmann, A., Muzalewski, P., Polonski, L., Kazik, A., Nowalany-Kozielska, E., Wojciechowska, C., Ponikowski, P., Nawrocka, S., Filipiak, K., Serafin, A., Dubiel, J., Mielecki, W., Ogorek, M., Kopcik, D., Jaworska, K., Skonieczny, G., Kawecka-Jaszcz, K., Bryniarski, L., Tracz, W., Lesniak-Sobelga, A., Jankielewicz, J., Zaluska, R., Trojnar, R., Kawalek, P., Gaciong, Z., Pulkowski, G., Anaszewicz, M., Samul, W., Adamus, J., Cholewa, M., Kubik, L., Szczechowicz, R., Rekosz, J., Kwiatkowska, D., Gajek, J., Mazurek, W., Kominek, M., Siminiak, T., Guzniczak, E., Monteiro, P., Providencia, L., Monteiro, S., Pinho, T., Gavina, C., Sousa, C., Loureiro, J., Ferreira, A.R., Cardoso, A., Araujo, J., Rebolo, I., Catarino, C., Santos, J., Nunes, L.P., Mimoso, J., Marques, N., Leitao, M., Pais, J., Fernandes, A., Diogo, A., Nóbrega, J., Moreira, J.I., Mateus, P., Oliveira, J., Selas, M., Ribeiro, V., Albuquerque, A., Reis, R., Ramos, A., Salazar, F., Nair, D., Ng, C.K., Yeo, D., Wong, A., Funiak, S., Belicova, M., Striezova, I., Krajci, P., Sojka, G., Herman, O., Zemberova, A., Pella, D., Fedacko, J., Banikova, A., Micko, K., Macek, V., Moscovic, M., Vahala, P., Vykoukalova, T., Dzupina, A., Marusakova, M., Stevlik, J., Akubzanova, E., Hatalova, K., Burgess, L., Coetzee, C., Mabin, T., Roos, J., Mohamed, Z., Pillay, T., Corbett, C., Bodenstein, W., Tayob, F., Ebrahim, I., Bolsman, C., Horak, A., Lloyd, E., Pretorius, M., Commerford, P., De Andrade, M., Roux, J., Murray, A., Soma, P., Delport, E., Cassel, G., Van Zyl, L., Cronje, T., Sarvan, M., Moodley, R., Guerra, M., Swanepoel, N., Bayat, J., Klug, E., Hellig, S., Yoon, J., Kim, J., Chung, W., Choi, Y., Cho, M., Lee, S., Kwon, H., Hong, B., Seung, K., Chang, K., Rha, S., Jeong, M.H., Hong, Y., Lee, C., Seong, I., Jeong, J., Tahk, S., Yoon, M., Chae, S.C., Kim, H., Lopez, V., Roldan, J.M., Mancisidor, P., Froufe, J., López, A., Franco, S., Molina, A., Soriano, F., Cobos, M., Mejía, H.D., Sanz, R., Vazquez, A., Garri, F., Esteban, I., Marco, P., Artaecheverria, J., Cequier, A., Esplugas, E., Gonzalez, J., de Sa, E., Armada, E., Worner, F., Hernández, I., Roncales, F., Gomollon, J., del Rio, A., Alameda, J., Basilio, E., Rafols, M., Ferres, R., Molla, C., Pascual, J., Cortada, J., García, C., Iglesias, G., Villa, E., Aros, F., Goya, I., Bueno, M., Pereira, R.V., Clavero, X., Pasaron, C.D., Jorda, R., Pereira, R., Perez, O., de Teresa, E., Navarro, M., de la Guia, F., Lozano, T., Antorrena, I., Aranda, M., Alonso, L., Mirelis, J., Alcasena, S., Paniagua, V.A., Juanatey, J., Gregorian, L., Munoz, J., Escorihuela, A., Sanz, A., Flores, A., Garcia, P.A., Alfonso, F., Marin, E., Lozano, A., Bethencourt, A., Grau, A., Rubio, A., Sala, J., Royuela, N., San Jose, J., Bugos, V., de Valdecilla, H., Martin, J., Jimenez, R., Felgueres, M., Escalera, P., Ruiz, R., Bescos, L., Sanchez, I., Chavarri, M., Casares, G., Johanson, P., Hultsberg-Olsson, G., Witt, N., Samad, B., Damm, T., Risenfors, M., Ortgren, L., Henareh, L., Jernberg, T., Berglund, M., Karlsson, J., Koch, A., Lycksell, M., Lundgren, C., Herlitz, J., Sjölin, M., Erlinge, D., Matson, E., Cizinsky, S., Carlsson, F., Ryttberg, B., Johansson, K., Tygesen, H., Bergsten, J., Naslund, U., Sundholm, C., Timberg, I., Wikström, P., Hårdhammar, P., Lisbeth, A., Lund, L., Hage, C., Rosenqvist, U., Grändås, M., Larsson, L., Hammerman, A., Andersson, G., Johansson, S., Bennermo, M., Tjerneld, H., Forsgren, M., Eriksson, K., Eriksson, M., Bengtsson, P.O., Yu, W., Ceder-Brolin, K., Stafberg, C., Andersson, E., Roussine, V., Ångman, K., Melin, B., Thorsen, S., Lundell, L., Buijs, F., Östberg, S., Sigaud, P., Moccetti, T., Bondio, M., Kuehlkamp, V., Pieper, M., Gallino, A., Zender, H., Genné, D., Gauthey, J., Wilhelm, M., Saner, H., Trachsel, L., Roethlisberger, C., Schlaepfer, H., Kujawski, T., Pagnamenta, A., Meyer-Monard, S., Krapf, R., Biedermann, B., Schneider, H., Rickli, H., Ramsay, D., Linka, A., Ballmer, P., Oswald, M., Girod, G., Charng, M., Shu-Ling, H., Ping-Han, L., Wu, C., Liu, S., Lin, M., Chian-Yi, W., Yeh, H., Mei-Juan, C., Hsieh, I., Wang, Y., Ural, E., Sahin, T., Yildiz, Z., Kayikcioglu, M., Kultursay, H., Yigit, Z., Calpar, I., Ata, N., Goktekin, O., Senol, U., Yalcin, R., Timurkaynak, T., Kaya, U., Yildirir, A., Karacaglar, E., Faynyk, A., Sorokivskyy, M., Koval, O., Kaplan, P., Kraiz, I., Popova, K., Kyyak, Y., Barnett, O., Karpenko, O., Todoriuk, L., Tseluyko, V., Kopytsya, M., Petyunina, O., Kovalskyy, I., Zhukova, Y., Katerenchuk, I., M'yakinkova, L., Lutay, Y., Syvolap, V., Kyselov, S., Vakaliuk, I., Nesterak, R., Nikonov, V., Feskov, O., Goloborodko, B., Golovtsev, Y., Berezniakov, I., Lebedynska, M., Rudenko, L., Tutov, I., Ahsan, A., Burton, J., Levy, T., Lakeman, N., Spratt, J., Langford, E., Sutcliffe, S., Khwanda, A., Davis, G., Rodrigues, E., Dickinson, D., Been, M., Trouton, T., Riddell, J., Moriarty, A., McEneaney, D., Squire, I., Narayan, H., Goode, G., Helliwell, L., Boos, C., Greaves, K., Knops, K., Pegge, N., Signy, M., Wong, Y., Moore, S., Fluck, D., Atkinson, C., Adgey, A., McKeag, N., Bishop, A., Glover, J., Barbir, M., Breen, J., Robson, H., Townend, J., Dwenger, E., Ekpo, E., Shakespeare, C., Barr, C., McClements, B., McAllister, A., De Belder, M., Cooke, J., Williams, S., Daniel, D., Pye, M., Griffith, K., Wright, L., Trevelyan, J., Doughty, A., Hughes, E., Phillips, C., Penny, W., Groves, P., Kardos, A., Purvis, J., McNeill, A., Jones, A., Brown, J., Saeed, B., Sprigings, D., Herity, N., Brown, C., Unks, M., Cauthren, T., Bertolet, B., Jones, M., Decker, S., Chambers, J., Stahlberg, J., Varma, S., Gencheff, N., Price, A., McElroy, D., Chu, A., Crutchfield, B., Eaton, G., Looney, A., Qureshi, M., Wilks, J., Drenning, D., Overman, A., Andreou, C., Russo, P., Stuckey, T., Pruitt, H., D'Urso, M., DeRaad, R., Rogers, W., Thorington, S., Pasquini, J., Iwaoka, R., Tannenbaum, M., Prouty, D., Wiseman, A., Sharow, A., Graham, B., Ali, M.I., Dale, H., Tarsi, D., Picone, M., Juarez, S., Hamroff, G., Hollenweger, L., Scirica, B., Sabatine, M., Marti, J., Perlman, R., Pavlides, A., Joffe, I., Albirini, A., Campbell, T., Puri, S., Lopez, C., Pearce, D., Shah, D., McPherson, J., Donegan, R., Murdock, D., Block, D., Malik, A., Musina, R., Dauber, I., Varner, C., Bach, R., Palazzolo, M., Bhalla, H., Thompson, M., Pollock, S., Johnson, S., Lipson, L., Brunk, S., Karas, S., Vicari, R., Kuvin, J., Mooney, P., Aycock, G., Lane, B., Sharma, M., Gibson, T., Chang, G., DiVito, P., Mehta, R., Watkins, K., Chiu, A., Gunderson, J., Tedder, B., Williams, P., Hage-Korban, E., Childs, A., Banerjee, S., Kazi, F., Bennett, J., Barnes, D., Wohns, D., Noorman, C., Aggarwal, K., Lau-Sickman, A., Paulowski, J., Amos, M., Rider, J., Fenton, S., Schantz, M., Hakas, J., Mcsorley, J., Felten, W., Bitzer, V., Russell, J., Loyo, J., Adjei, A., Mehta, K., Uretsky, B., Hale, M., Shaikh, S., Miller, M., Hollenbaugh, D., Crawford, K., Fortuin, D., Galindo, A., Del Core, M., Butkus, E., Collins, J., Prior, J., Hahn, R., Greene-Nashold, J., Alexander, J., Genova, E., MacDonell, A., Broadwater, S., Kereiakes, D., White, D., Lopez, M., Schenks, R., Lui, H., Gibbons, P., Davis, B., Thornton, K., Daley, P., Budzon, S., McCullum, K., Delio-Cox, B., Nadar, V., Keim, S., McLaurin, B., Davis, C., Betzu, R., Al-Jumaily, J., Bolli, R., Alshaher, M., Leesar, M., Collins, T., Akkad, H., Bilazarian, S., Marsters, M., Kennett, J., Melegrito, K., Mostel, E., Harris, R., Chang, M., Hatfield, G., Makam, S., Garvey, M., Levite, H., White, J., Abdel-Latief, A., Pelletier, L., Carr, K., Mckenna, K., De Lemos, J., Soto, G., Kozina, J., Harris, D., Vlastaris, A., Bittel, B., Riba, A., Gugudis, J., Singh, N., Qureshi, I., Doty, W., Lehmann, J., Lieber, I., Martin, S., Nicu, M., Bhalodkar, N., Ravi, P., Canto, J., Bass, M., Campbell, C., Steinhubl, S., Moles, K., Harjai, K., Stapleton, D.D., Hoey, K., Erwin, J., Fikes, W., Stein, B., Sabatino, K., Teklinski, A., Colfer, H., Ward, P., Langevin, E., Faucett, S., Mamdani, S., DeSimone, L., Tuohy, E., Cullen, T., Eisenberg, S., Chronos, N., Allen, R.P., Erickson, B., Mahon, K., Kirby, A., Siegel, C., Stroud, L., Johnson, J., Panchal, V., Pearson, A., Abell, T., De Gregorio, M., Boomer, L., Vahdat, O., VanNatta, B., Long, P., Chalavarya, G., Skatrud, L., Carey, C., Wright, W., Mechem, C., Matthews, B., Adams, A., Vora, K., Wead, J., Koren, M., Gregory, D., El Khadra, M., 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K., Bayles, A., Masroor, M., North, W.K., Fishberg, R., Merveil-Ceneus, B., Butcher, R., Menapace, F., Kilbride, S., Ramabadran, R.S., Loukinen, K., Khalil, J., Ramabadran, R., Walsh, S., Gill, S., Cyncar, R., McLachlan, J., Surakanti, V., Rusterholtz, L., Shoukfeh, F., Stephenson, L., Tsang, M., Nolan, V., Gilchrist, I., Jefferson, D., Feldman, T., Reyes, L., Santos, R., Little, W., Wesley, D., Gharib, W., Mendell, A., Esham, G., Kakavas, P., Whitcomb, C., Book, K., Bazzi, A., Alvarez, J., Cohen, Y., Ayres, T., Rhule, V., Labib, A., Schuler, P., Zughaib, M., Telck, K., Bikkina, M., Turnbull, K., Sharma, T., Orosz, S., Shah, R., Petrino, M., Hughes, M., Hershey, J., Hudock, D., Hui, P., Von Bakonyi, A., Arnold, A., Kappel, D., Pennock, G., Cloud, B., Tucker, K., Harp, L., Hoover, C., Eisenhauer, M., Roth, J., Young, C., Thai, H., Escalante, A., Bautista, J., Gazmuri, R., Nyland, J., Cubeddu, L., DeFranco, A., Dias, D., Fielding, M., Reeves, R., Hermany, P., Meissner-Dengler, S., Evans, M., Flores, E., Tannenbaum, A., McGarr, K., Moran, J., Stout, E., Allred, S., Henderson, D., Crandall, L., Strote, J., Voyles, W., Robeson, D., Bedoya, R., Omar, B., Pettyjohn, F., Revere, C., Coy, K., Margolis, J., Sotolongo, C., Scheffel, M., Munir, A., Shirwany, A., Douglas, L., Girala, R., Humphreys, R., Agarwal, J., Bankowski, D., Watson, R., Bishop, B., Klementowicz, P., Blais, D., Cohen, B., Lobur, E., Dimenna, J., Dempsey, K., Izzo, M., Bondi, L., Carell, E., Eaton, C., Saltiel, F., Grewal, G., Connolly, T., Little, T., Wiegman, P., Gips, S., Held, J., Paraschos, A., Quesada, R., Goudreau, E., Sears, M., Istfan, P., Holt, S., McClung, J., Nguyen, N., Quintana, O., Gottlieb, D., Knutson, T., Barringhaus, K., Lester, F., Sullivan, P., Rodriguez-Ospina, L., Cannon, C.P., Blazing, M.A., Giugliano, R.P., McCagg, A., White, J.A., Lewis, B.S., Jukema, J.W., De Lucca, P., Im, K., Bohula, E.A., Reist, C., Wiviott, S.D., Tershakovec, A.M., Musliner, T.A., Braunwald, E., Califf, R.M., IMPROVE-IT Investigators, Musliner, T., Tershakovec, A., Gurfinkel, E., Aylward, P., Tonkin, A., Maurer, G., Van de Werf, F., Nicolau, J.C., Theroux, P., Genest, J., Armstrong, P., Corbalan, R., Isaza, D., Spinar, J., Grande, P., Voitk, J., Kesaniemi, A., Bassand, J.P., Farnier, M., Darius, H., Keltai, M., Mathur, A., Mittal, S., Reddy, K., Lewis, B., De Ferrari, G.M., Ophuis, T.O., Jukema, J., White, H., Pedersen, T., Britto, F., Ruzyllo, W., Carrageta, M., Duris, T., Dalby, A., Seung, K.B., Lopez-Sendon, J., Dellborg, M., Mach, F., Guneri, S., Parkhomenko, A., Brady, A., Cannon, C., Blazing, M., Ballantyne, C., de Lemos, J., Kleiman, N., McGuire, D.K., Centeno, E., Casalins, M., Cartasegna, L., Beltrano, M.C., Guerrero, R., Fanuele, M., Berra, F., Egido, J., Colombo, H., Dellatorre, M., Terns, P., Blumberg, E., Reges, P., Azize, G., Ramos, H., Fernandez, R., Carlessi, C., Milesi, R., Schmuck, R., Duronto, E., Procopio, G., Carlevaro, O., Maffeo, H., Beloscar, J., Viso, M., Hominal, M., Castoldi, M., Bluguermann, J., Mauro, D., Macin, S., Cocco, N., Ruiz, N., Ricart, J., Lozada, A., Nani, S., Turri, D., Fernandez, H., Caruso, O., Zarandon, R., Bono, J., Arias, V., Allall, O., Marino, J., Cusimano, S., Schygiel, P., Buzetti, C., Penaloza, N., Berli, M., Worthley, S., Roach, A., Chew, D., Wright, T., Leitch, J., Hicks, E., Rankin, J., Venn-Edmonds, C., Lehman, R., Morrison, H., Shaw, J., Mak, V., Hii, C., Smith, K., Cross, D., Lilwall, L., Nelson, G., Loxton, A., Horowitz, J., Rose, J., Steinwender, C., Leisch, F., Kammler, J., Brussee, H., Zweiker, R., Niederl, E., Weihs, W., Giorgio, G., Lang, I., Drexel, H., Zanolin, D., Hoppe, U., Atzenhofer-Baumgartner, K., Pichler, M., Hainzer, D., Eber, B., Pichler, F., Foeger, B., Wechselberger, T., Mayr, H., Hofer, J., Stockenhuber, F., Warlits, B., Huber, K., Egger, F., Weidinger, F., Ziegler, B., Jirak, P., Metzler, B., Pachinger, O., Wanitschek, M., Auer, J., Grabscheit, G., Podczeck-Schweighofer, A., Priesnitz, T., Frank, H., El Allaf, D., Marechal, P., Roosen, J., Joly, E., Lefebvre, P., Arend, C., Sinnaeve, P., De Velder, L., Hellemans, S., Vanhauwaert, B., Van Dorpe, A., Heyse, A., Vantomme, C., Striekwold, H., Van Den Broeck, D., Lancellotti, P., Schoors, D., Lemoine, I., Taeymans, Y., De Wolf, L., Brike, C., Vercauteren, S., Tahon, S., Vervoort, G., Mestdagh, I., Pirenne, B., Cardinal, F., Lips, S., Dujardin, K., Debrouwer, K., Dhooghe, G., Holvoet, G., van de Borne, P., Renard, M., De Clippel, M., Lesseliers, H., Van Miert, N., Saraiva, J., Vicente, C., Rossi, P., Dos Santos, L.B., Duda, N., Tognon, A.P., Serrano, C., Gomes, F.L., Manenti, E.R., Silveira, D.S., Maia, L., Mouco, O.M., Paiva, M., Antonangelo, A., de Souza, J., Lino, E.A., Leães, P., Blacher, M.G., Kormann, A., Ultramari, F.T., Dutra, O., Mendelski, A.M., Morgado, S., Ardito, W., Greque, G., Ardito, R.V., Pimentel Filho, P., Zucchetti, C., Alves, A., Seabra, A.M., Mattos, M., Miranda, L.F., Silva, D., Uehara, R.M., Marin Neto, 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David, M., Giannoccaro, J., Beresford, P., Polasek, P., Roberts, P., Doucet, M., Beaudry, M., Cheung, S., Cleveland, T., Bhargava, R., McCallum, A., Ma, P., Morrissette, J., Cleveland, D., Chadwyn, D., Nigro, F., Weeks, A., Cryderman, C., Leader, R., Houde, G., Rousseau, S., Pearce, M., Radyk, M., Lonn, E., Magi, A., Lefkowitz, C., Sandrin, F., Coffin, N., Lubelsky, B., Coldwell, J., Habot, J., McPherson, C., De Larochelliere, R., Roy, M., Haichin, R., Barber, C., Bhesania, T., Kitagawa, H., To, T., Donnelly, B., Tymchak, W., Harris, L., Kouz, S., Huynh, T., St Jacques, B., Lamy, A., Rizzo, A., Stein, J., Childs, C., Wong, B., Poirier, R., Gupta, M., Dela Cruz, C., Constance, C., Gauthier, M., Ervin, F., Ouellette, M., Kokis, A., Lemay, C., Kwok, K., Leung, C., Lee, D., Nesmith, J., Renton, J., Syan, G., Turek, M., Hogan, D., Griffin, P., Lipson, A., Winestock, J., Abramson, B., Fogel, A., Gagne, C., Bergeron, J., Clarke, A., Slipp, S., Darcel, I., Carling-Chambers, L., Kannampuzha, P., Pallie, S., Krekorian, S., Vertes, G., Roth, S., Lai, K., Heath, J., Perez, L., Arriagada, G., Castro, P., Villa, F., Rodríguez, M., Ramos, G., Baraona, F., Núñez, A., García, M., Jofre, C., Silva, P., Lamich, R., Yovaniniz, P., Escobar, E., Dussaubat, A., Segura, E., Ramirez, M., Lapostol, C., Palma, A., Encina, L., Zapata, M., Baeza, N., Varela, P., Pérez, L., Jaramillo, C., Ruiz, S., Sanchez, G., Perdomo, I., Manzur, F., Cohen, L.E., Velasquez, J., Arana, C., Alvarez, Y., Triana, M., Balaguera, J., de Salazar, D., Rendon, N., Botero, R., Ruiz, A., Saaibi, J., Medina, J., Jaramillo, M., Calderón, M.J., Delgado, J., Bohorquez, R., Medina, M.F., Herrera, M., Rosales, D., Mendoza, F., Martinez, S., Ternera, A., Castro, R., Baiz, A., Martinez, M., Orozco, A., Suarez, M., Fonseca, Y., Beltran, R., Cepeda, M., Jaramillo, N., Valenzuela, C., Gutierrez, M., Sanchez, A., Vitovec, J., Hlinomaz, O., Poloczek, M., Mayer, O., Veselka, J., Vejvoda, J., Soucek, M., Spac, J., Novobilsky, K., 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Szelényi, Z., Polgár, P., Svab, S., Herczeg, B., Bajcsi, É., Vértes, A., Davidovits, S., Nagy, A., Király, C., Lupkovics, G., Kenéz, A., Poór, F., Takács, J., Kirschner, R., Simonyi, G., Koncz, J., Édes, I., Gergely, S., Katona, A., Nagy, E., Kovács, Z., Gyetvai, I., Salamon, C., Kolman, É., Sitkei, É., Csapó, K., Molnar, K., Mező, I., Sereg, M., Reddy, P., Manjunath, C., Narayanappa, S., Kumar, S., Sinha, N., Kapoor, A., Christopher, J., Reddy, G., Rani, M., Oomman, A., Ramamurthee, K., Kumar, N., Pasha, S.S., Rao, C., Murty, G.S., Chopra, A., Kapila, D., Bali, H., Chattree, K., Hasan, O., Suryaprakash, G., Rao, D., Babu, R., Bhargavi, M., Naik, S., Khan, S., Chopra, V., Sapra, R., Kaul, U., Ghose, T., Menon, R., Battikadi, S., Mullasari, A., Subban, V.K., Dani, S., Iby, M., Chandra, P., Sethi, S., Bhargava, M., Arora, P., Tyagi, G., Padmanabhan, T., Malhotra, S., Talwar, K., Shafiq, N., Kasliwal, R., Bansal, M., Eldar, M., Berger, M., Shechter, M., Atar, S., Roguin, N., Kilimnik, M., 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Ieva, R., Fattore, L., Cicia, G., Cavallini, C., Tamburino, C., Sacco, A., Mafrici, A., Di Pasquale, G., Pavesi, P.C., Scioli, R., Lioy, E., Occhiuzzi, E., Matino, M.G., Russo, V., Moscogiuri, M.G., Cuccia, C., Forgione, C., Volpe, M., Palano, F., Branca, G., Rossi, R., Modena, M., Olaru, I.A., Zanini, R., Cianflone, D., Cristell, N., Pantaleoni, M., Guiducci, U., Menozzi, C., Gaddi, O., Fasulo, A., Indolfi, C., Emanuele, V., Guerra, F., Iliceto, S., Marotta, C., Morocutti, G., Presbitero, P., Rossi, M., Bonatti, S., Grieco, A., Chiodi, L., Betti, I., Zuppiroli, A., Fanelli, R., Stanco, G., Azzolini, P., Ruggieri, C., Bocconcelli, P., Airoldi, F., Tavano, D., Brunelli, C., Caso, P., Scalzone, A., Ghigliotti, G., Facciorusso, A., Sim, K., Kiam, O., Chee, K., Bin Ismail, O., Zambahari, R., Ophuis, T., van Nes, E., Werter, C.J., Ophuis, A.J., Troquay, R.P., Hamer, B.J., Lenderink, T., Feld, R.J., van Hessen, M.W., Viergever, E.P., van der Sluis, A., Lok, D.J., Badings, E.A., Nierop, P.R., Danse, I.Y., Hermans, W.R., Holwerda, N.J., Thijssen, H.J., Theunissen, L.J., van der Zwaan, C., Van Den Berg, B.J., Hendriks, I.H., Ronner, E., Withagen, A.J., Dijkshoorn-Giesen, A.H., Ezechiels, J.P., Kuijper, A.F., Den Hartog, F.R., Van Kalmthout, P.M., Buijs, E.M., van der Zeijst, M., Zwart, P.A., Zuidgeest, J.A., van Eck, M., Daniels, M.C., van der Ven-Elzebroek, N., Van 't Hof, A., van Boven, A.J., van der Weerdt, A., Dunselman, P.H., Alings, M.A., van Es, R.F., The, S.H., Gurlek, C., Liem, A.H., van Lennep, H.W., Van Vlies, B., Kalkman, C., Swart, H.P., van der Bij, P., Taverne, R., Ciampricotti, R., van Dam, C., Spierenburg, H., van Ruijven, I., van Kempen, L.H., Willems, F.F., Dirkali, A., Stoel, I., Plomp, J., Veldmeijer, S., Tjeerdsma, G., Nijmeijer, R., Van Hal, J.M., Bartels, G.L., Posma, J.L., Linssen, G.C., Fauser, C.G., Waalewijn, R.A., Groenemeijer, B.E., Pos, L., Fast, J.H., Droste, H.T., Westenburg, J., Veenstra, W., Koolen, J., van Loo, L.W., Smits, W., Milhous, J.G., van Rossum, P., Stuij, S., Scott, R., Richards, A.M., Morrison, Z., Devlin, G., Fisher, R., Stewart, R., Benetar, J., Voss, J., Wong, S., Scott, D., Luke, R., Tang, E., Davidson, L., Hamer, A., Wilson, S., Price, R., Hart, H., Turner, A., Jortveit, J., Calic, S., Gundersen, T., Brunvand, H., Fosse, L., Nygaard, O., Gjellefall, B., Gravdal, S.A., Ringstad, R., Atar, D., Clausen, H., Hysing, J., Arvesen, K., Topper, M., Flagstad, E., Graven, T., Haug, H.H., Dalin, L., Al-Ani, R., Otterstad, J., Ausen, K., Aaser, E., Olufsen, M., Halvorsen, S., Gullestad, L., Stueflotten, W., Waage, K., Stødle, R.M., Hall, C., Aase, O., Nordeng, J., Soyland, E., Fageraas, E.R., Lied, A., Aske, R., Raouf, N., Johansson, J., Herrscher, T., Skogrand, E., Bjornstad, H., Aagnes, I., Arntsen, B.I., Vegsundvaag, J., Skjold, M.E., Velle, H., Aambakk, M.B., Skjetne, O., Byfuglien, A., Rodriguez, J., Galvez, D., Medina, F., Hernandez, H.A., Chavez, V., Morales, R., Huapalla, E., Velasquez, D., Torres, F., 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- Abstract
Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years. The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P=0.016). Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benef
- Published
- 2015
8. Selection of patients of reperfusion therapy for individual patients with evolving myocardial infarction
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Werf, F. van de, Vahanian, A., Gulba, D.C., Muller, J., Arnold, A.E.R., Bär, F., Vermeer, F., Verheugt, F.W.A., Boersma, H., Vanes, G.A., Deckers, J.W., Lenderink, T., Simoons, M.L., Steyerberg, E.W., Zwaan, C. van der, Boer, M.J. de, Zijlstra, F., Wilcox, R., Sleight, P., Selker, H.P., Califf, R.M., Granger, C., Lee, K.L., Ohman, M.E., Weaver, D.W., Love, T., White, H., and Collins, R.
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Reperfusion therapy in acute coronary syndromes ,Reperfusietherapie bij acute coronaire syndromen - Abstract
Item does not contain fulltext
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- 1997
9. Role of diuretics, blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study
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Shen, L., Shah, B.R., Reyes, E.M., Thomas, L., Wojdyla, D., Diem, P., Leiter, L.A., Charbonnel, B., Mareev, V., Horton, E.S., Haffner, S.M., Soska, V., Holman, R., Bethel, M.A., Schaper, F., Sun, J.-L., McMurray, J.J.V., Califf, R.M., and Krum, H.
- Abstract
Objective To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes.\ud \ud Design Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial.\ud \ud Setting NAVIGATOR trial.\ud \ud Participants Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control.\ud \ud Main outcome measures Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment.\ud \ud Results During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively).\ud \ud Conclusions Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant.
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- 2013
10. Effect of valsartan on the incidence of diabetes and cardiovascular events
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McMurray, J.J., Holman, R.R., et al., X, Rutten, G.E.H.M., NAVIGATOR Study Group, x, and Califf, R.M.
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- 2010
11. Effect of nateglinide on the incidence of diabetes and cardiovascular events
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Holman, R.R., Haffner, S.M., et al., X, Rutten, G.E.H.M., NAVIGATOR Study Group, x, and Califf, R.M.
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- 2010
12. Safety and efficacy of enoxaparin vs unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes who receive tirofiban and aspirin: a randomized controlled trial
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Blazing, M.A., Lemos, J.A. de, White, H.D., Fox, K., Verheugt, F.W.A., Ardissino, D., DiBattiste, P.M., Palmisano, J., Bilheimer, D.W., Snapinn, S.M., Ramsey, K.E., Gardner, L.H., Hasselblad, V., Pfeffer, M.A., Lewis, E.F., Braunwald, E., and Califf, R.M.
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Heart, lung and circulation [UMCN 2.1] - Abstract
Contains fulltext : 59322.pdf (Publisher’s version ) (Closed access) CONTEXT: Enoxaparin or the combination of glycoprotein IIb/IIIa inhibitor tirofiban with unfractionated heparin independently have shown superior efficacy over unfractionated heparin alone in patients with non-ST-elevation acute coronary syndromes (ACS). It is not clear if combining enoxaparin with glycoprotein IIb/IIIa inhibitors is as safe or as effective as the current standard combination of unfractionated heparin with glycoprotein IIb/IIIa inhibitors. OBJECTIVE: To assess efficacy and safety of the combination of enoxaparin and tirofiban compared with unfractionated heparin and tirofiban in patients with non-ST-elevation ACS. DESIGN, SETTING, AND PARTICIPANTS: A prospective, international, open-label, randomized, noninferiority trial of 1 mg/kg of enoxaparin every 12 hours (n = 2026) compared with weight-adjusted intravenous unfractionated heparin (n = 1961) in patients with non-ST-elevation ACS receiving tirofiban and aspirin. Phase A of the A to Z trial was conducted between December 1999 and May 2002. MAIN OUTCOME MEASURES: Death, recurrent myocardial infarction, or refractory ischemia at 7 days in the intent-to-treat population with boundaries set for superiority and noninferiority. Safety based on measures of bleeding using the Thrombolysis in Myocardial Infarction (TIMI) classification system. RESULTS: A total of 169 (8.4%) of 2018 patients randomized to enoxaparin experienced death, myocardial infarction, or refractory ischemia at 7 days compared with 184 (9.4%) of 1952 patients randomized to unfractionated heparin (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.71-1.08). This met the prespecified criterion for noninferiority. All components of the composite primary and secondary end points favored enoxaparin except death, which occurred in only 1% of patients (23 for enoxaparin and 17 for unfractionated heparin). Rates for any TIMI grade bleeding were low (3.0% for enoxaparin and 2.2% for unfractionated heparin; P =.13). Using a worst-case approach that combined 2 independent bleeding evaluations, use of enoxaparin was associated with 1 additional TIMI major bleeding episode for each 200 patients treated. CONCLUSIONS: In patients receiving tirofiban and aspirin, enoxaparin is a suitable alternative to unfractionated heparin for treatment of non-ST-elevation ACS. The 12% relative and 1% absolute reductions in the primary end point in favor of enoxaparin met criterion for noninferiority and are consistent with prior trials performed without the use of glycoprotein IIb/IIIa inhibitors.
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- 2004
13. Population pharmacokinetics and pharmacodynamics of rivaroxaban in patients with non‐valvular atrial fibrillation: Results from ROCKET AF
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Girgis, I.G., primary, Patel, M.R., additional, Peters, G.R., additional, Moore, K.T., additional, Mahaffey, K.W., additional, Nessel, C.C., additional, Halperin, J.L., additional, Califf, R.M., additional, Fox, K.A.A., additional, and Becker, R.C., additional
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- 2014
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14. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both
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Pfeffer, M.A., McMurray, J.J., Velazquez, E.J., Rouleau, J.L., Kober, L., Maggioni, A.P., Solomon, S.D., Swedberg, K., Van de Werf, F., White, H., Leimberger, J.D., Henis, M., Edwards, S., Zelenkofske, S., Sellers, M.A., Califf, R.M., and nullinAcuteMyocardialInfarctionTrialInvestigators., Valsartan
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- 2003
15. Predictors of stroke in patients with impaired glucose tolerance: results from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research trial
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Preiss, D., Giles, T.D., Thomas, L.E., Sun, J.L., Haffner, S.M., Holman, R.R., Standl, E., Mazzone, T., Rutten, G.E.H.M., Tognoni, G., Chiang, F.T., McMurray, J.J., Califf, R.M., Preiss, D., Giles, T.D., Thomas, L.E., Sun, J.L., Haffner, S.M., Holman, R.R., Standl, E., Mazzone, T., Rutten, G.E.H.M., Tognoni, G., Chiang, F.T., McMurray, J.J., and Califf, R.M.
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- 2013
16. Incidence of atrial fibrillation in a population with impaired glucose tolerance: The contribution of glucose metabolism and other risk factors. A post hoc analysis of the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research trial
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Latini, R., Staszewsky, L., Sun, J.L., Bethel, M.A., Disertori, M., Haffner, S.M., Holman, R.R., Chang, F., Giles, T.D., Maggioni, A.P., Rutten, G.E.H.M., Standl, E., Thomas, L., Tognoni, G., Califf, R.M., McMurray, J.J., Latini, R., Staszewsky, L., Sun, J.L., Bethel, M.A., Disertori, M., Haffner, S.M., Holman, R.R., Chang, F., Giles, T.D., Maggioni, A.P., Rutten, G.E.H.M., Standl, E., Thomas, L., Tognoni, G., Califf, R.M., and McMurray, J.J.
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- 2013
17. Incidence of atrial fibrillation in a population with impaired glucose tolerance: The contribution of glucose metabolism and other risk factors. A post hoc analysis of the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research trial
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Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, General Practice & Nursing Science, Latini, R., Staszewsky, L., Sun, J.L., Bethel, M.A., Disertori, M., Haffner, S.M., Holman, R.R., Chang, F., Giles, T.D., Maggioni, A.P., Rutten, G.E.H.M., Standl, E., Thomas, L., Tognoni, G., Califf, R.M., McMurray, J.J., Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, General Practice & Nursing Science, Latini, R., Staszewsky, L., Sun, J.L., Bethel, M.A., Disertori, M., Haffner, S.M., Holman, R.R., Chang, F., Giles, T.D., Maggioni, A.P., Rutten, G.E.H.M., Standl, E., Thomas, L., Tognoni, G., Califf, R.M., and McMurray, J.J.
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- 2013
18. Changing the diagnosis of acute myocardial infarction: Implications for practice and clinical investigations
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Newby, L.K., Alpert, J.S., Ohman, E.M., Thygesen, Kristian Anton, and Califf, R.M.
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- 2002
19. Thrombin-specific anticoagulation with bivalirudin versus heparin in patients receiving fibrinolytic therapy for acute myocardial infarction: the HERO-2 randomized trial
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White, H.D., Simes, R.J., Aylward, P.E.G., Armstrong, P.W., Califf, R.M., French, J.K., Granger, C.B., Marschner, I.C., Topol, E.J., Van de Werf, F.J., and Wilcox, R.G.
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acute myocardial infarction ,treatment ,bivalirudin - Abstract
The combination of fibrinolytic therapy and heparin for acute myocardial infarction fails to achieve reperfusion in 40-70% of patients, and early reocclusion occurs in a substantial number. We did a randomised, open-label trial to compare the thrombin-specific anticoagulant, bivalirudin, with heparin in patients undergoing fibrinolysis with streptokinase for acute myocardial infarction. Bivalirudin did not reduce mortality compared with unfractionated heparin, but did reduce the rate of adjudicated reinfarction within 96 h by 30%. Small absolute increases were seen in mild and moderate bleeding in patients given bivalirudin. Bivalirudin is a new anticoagulant treatment option in patients with acute myocardial infarction treated with streptokinase.
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- 2001
20. Characteristics of clinical trials registered in ClinicalTrials.gov, 2007-2010
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Califf, R.M., Zarin, D.A., Kramer, J.M., Sherman, R.E., Aberle, L.H., Tasneem, A., Califf, R.M., Zarin, D.A., Kramer, J.M., Sherman, R.E., Aberle, L.H., and Tasneem, A.
- Abstract
Item does not contain fulltext, CONTEXT: Recent reports highlight gaps between guidelines-based treatment recommendations and evidence from clinical trials that supports those recommendations. Strengthened reporting requirements for studies registered with ClinicalTrials.gov enable a comprehensive evaluation of the national trials portfolio. OBJECTIVE: To examine fundamental characteristics of interventional clinical trials registered in the ClinicalTrials.gov database. METHODS: A data set comprising 96,346 clinical studies from ClinicalTrials.gov was downloaded on September 27, 2010, and entered into a relational database to analyze aggregate data. Interventional trials were identified and analyses were focused on 3 clinical specialties-cardiovascular, mental health, and oncology-that together encompass the largest number of disability-adjusted life-years lost in the United States. MAIN OUTCOME MEASURES: Characteristics of registered clinical trials as reported data elements in the trial registry; how those characteristics have changed over time; differences in characteristics as a function of clinical specialty; and factors associated with use of randomization, blinding, and data monitoring committees (DMCs). RESULTS: The number of registered interventional clinical trials increased from 28,881 (October 2004-September 2007) to 40,970 (October 2007-September 2010), and the number of missing data elements has generally declined. Most interventional trials registered between 2007 and 2010 were small, with 62% enrolling 100 or fewer participants. Many clinical trials were single-center (66%; 24,788/37,520) and funded by organizations other than industry or the National Institutes of Health (NIH) (47%; 17,592/37,520). Heterogeneity in the reported methods by clinical specialty; sponsor type; and the reported use of DMCs, randomization, and blinding was evident. For example, reported use of DMCs was less common in industry-sponsored vs NIH-sponsored trials (adjusted odds ratio [OR], 0.11; 95% CI, 0.09
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- 2012
21. Impediments to clinical research in the United States
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Kramer, J.M., Smith, P.B., Califf, R.M., Kramer, J.M., Smith, P.B., and Califf, R.M.
- Abstract
Item does not contain fulltext, Clinical trials are essential to the evaluation of promising scientific discoveries, but they are becoming unsustainably burdensome, threatening to deprive patients and health-care providers of new therapies and new evidence to guide the use of existing treatments. Regulations are often blamed for impeding clinical research, but there are other elements of the clinical trials enterprise that also have the potential to add burdens, through either imposed requirements or incentives that do not favor clinical research (Figure 1).
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- 2012
22. Comparison of sibrafiban with aspirin for prevention of cardiovascular events after acute coronary syndromes: a randomised trial
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Topol, E., Califf, R.M., Simes, R.J., Werf, F. van de, Diaz, R., Paoloasso, E., Aylward, P., Keech, A., Klein, W., Piegas, L., Tomov, I., Armstrong, P.W., Widimsky, P., Grande, P., Halinen, M., Vahanian, A., Neuhaus, K., Dimas, A.P., White, H., Preda, I., Kristinsson, A., Ardissino, D., Tzivoni, D., Madsen, S., Sugrue, D., Sadowski, Z., Seabra-Gomes, R., Apetrei, E., Dalby, A., Betriu, A., Pfisterer, M., Verheugt, F.W.A., Fox, K., Bates, E.R., Gibler, W.B., Granger, C., Harrington, R.A., Hochman, J.S., Holmes, D.R., Kleiman, N.S., Lee, K.L., Molietrno, D.J., Newby, L.K., and Ohman, E.M.
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Reperfusion therapy in acute coronary syndromes ,Reperfusietherapie bij acute coronaire syndromen - Abstract
Item does not contain fulltext 15 p.
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- 2000
23. Effect of Nesiritide in Patients with Acute Decompensated Heart Failure
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OConnor, C.M., Starling, R.C., Hernandez, A.F., Armstrong, P.W., Dickstein, K., Hasselblad, V., Heizer, G.M., Komajda, M., Massie, B.M., McMurray, J.J. V., Nieminen, M.S., Reist, C.J., Rouleau, J.L., Swedberg, K., Adams, K.F., Anker, S.D., Atar, D., Battler, A., Botero, R., Bohidar, N.R., Butler, J., Clausell, N., Corbalan, R., Costanzo, M.R., Dahlström, Ulf, Deckelbaum, L.I., Diaz, R., Dunlap, M.E., Ezekowitz, J.A., Feldman, D., Felker, G.M., Fonarow, G.C., Gennevois, D., Gottlieb, S.S., Hill, J.A., Hollander, J.E., Howlett, J.G., Hudson, M.P., Kociol, R.D., Krum, H., Laucevicius, A., Levy, W.C., Mendez, G.F., Metra, M., Mittal, S., Oh, B.-H., Pereira, N.L., Ponikowski, P., Wilson, W.H., Tanomsup, S., Teerlink, J.R., Triposkiadis, F., Troughton, R.W., Voors, A.A., Whellan, D.J., Zannad, F., Califf, R.M., OConnor, C.M., Starling, R.C., Hernandez, A.F., Armstrong, P.W., Dickstein, K., Hasselblad, V., Heizer, G.M., Komajda, M., Massie, B.M., McMurray, J.J. V., Nieminen, M.S., Reist, C.J., Rouleau, J.L., Swedberg, K., Adams, K.F., Anker, S.D., Atar, D., Battler, A., Botero, R., Bohidar, N.R., Butler, J., Clausell, N., Corbalan, R., Costanzo, M.R., Dahlström, Ulf, Deckelbaum, L.I., Diaz, R., Dunlap, M.E., Ezekowitz, J.A., Feldman, D., Felker, G.M., Fonarow, G.C., Gennevois, D., Gottlieb, S.S., Hill, J.A., Hollander, J.E., Howlett, J.G., Hudson, M.P., Kociol, R.D., Krum, H., Laucevicius, A., Levy, W.C., Mendez, G.F., Metra, M., Mittal, S., Oh, B.-H., Pereira, N.L., Ponikowski, P., Wilson, W.H., Tanomsup, S., Teerlink, J.R., Triposkiadis, F., Troughton, R.W., Voors, A.A., Whellan, D.J., Zannad, F., and Califf, R.M.
- Abstract
Background Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. Methods We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. Results Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P = 0.03) and 24 hours (68.2% vs. 66.1%, P = 0.007), but the prespecified level for significance (P = 0.005 for both assessments or Pd less than= 0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P = 0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P = 0.11). Conclusions Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot b
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- 2011
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24. Effect of valsartan on the incidence of diabetes and cardiovascular events
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Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, General Practice & Nursing Science, McMurray, J.J., Holman, R.R., et al., X, Rutten, G.E.H.M., NAVIGATOR Study Group, x, Califf, R.M., Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, General Practice & Nursing Science, McMurray, J.J., Holman, R.R., et al., X, Rutten, G.E.H.M., NAVIGATOR Study Group, x, and Califf, R.M.
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- 2010
25. Effect of nateglinide on the incidence of diabetes and cardiovascular events
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Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, General Practice & Nursing Science, Holman, R.R., Haffner, S.M., et al., X, Rutten, G.E.H.M., NAVIGATOR Study Group, x, Califf, R.M., Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, General Practice & Nursing Science, Holman, R.R., Haffner, S.M., et al., X, Rutten, G.E.H.M., NAVIGATOR Study Group, x, and Califf, R.M.
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- 2010
26. Effects of platelet glycoprotein IIb/IIIa receptor blockers in non-ST segment elevation acute coronary syndromes: benefit and harm in different age subgroups
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Hernández, A.V. (Adrián), Westerhout, C.M. (Cynthia), Steyerberg, E.W. (Ewout), Bueno, H. (Hector), White, H.D. (Harvey), Théroux, P. (Pierre), Moliterno, D.J. (David), Armstrong, P.W. (Paul), Califf, R.M. (Robert), Wallentin, L.C. (Lars), Simoons, M.L. (Maarten), Boersma, H. (Eric), Hernández, A.V. (Adrián), Westerhout, C.M. (Cynthia), Steyerberg, E.W. (Ewout), Bueno, H. (Hector), White, H.D. (Harvey), Théroux, P. (Pierre), Moliterno, D.J. (David), Armstrong, P.W. (Paul), Califf, R.M. (Robert), Wallentin, L.C. (Lars), Simoons, M.L. (Maarten), and Boersma, H. (Eric)
- Abstract
Objective: To investigate whether the beneficial and harmful effects of platelet glycoprotein IIb/IIIa receptor blockers in non-ST elevation acute coronary syndromes (NSTE-ACS) depend on age. Methods: A meta-analysis of six trials of platelet glycoprotein IIb/IIIa receptor blockers in patients with NSTE-ACS (PRISM, PRISM-PLUS, PARAGON-A, PURSUIT, PARAGON-B, GUSTO IV-ACS; n = 31 402) was performed. We applied multivariable logistic regression analyses to evaluate the drug effects on death or non-fatal myocardial infarction at 30 days, and on major bleeding, by age subgroups (<60, 60–69, 70–79, >=80 years). We quantified the reduction of death or myocardial infarction as the number needed to treat (NNT), and the increase of major bleeding as the number needed to harm (NNH). Results: Subgroups had 11 155 (35%), 9727 (31%), 8468 (27%) and 2049 (7%) patients, respectively. The relative benefit of platelet glycoprotein IIb/IIIa receptor blockers did not differ significantly (p = 0.5) between age subgroups (OR (95% CI) for death or myocardial infarction: 0.86 (0.74 to 0.99), 0.90 (0.80 to 1.02), 0.97 (0.86 to 1.10), 0.90 (0.73 to 1.16); overall 0.91 (0.86 to 0.99). ORs for major bleeding were 1.9 (1.3 to 2.8), 1.9 (1.4 to 2.7), 1.6 (1.2 to 2.1) and 2.5 (1.5–4.1). Overall NNT was 105, and overall NNH was 90. The oldest patients had larger absolute increases in major bleeding, but also had the largest absolute reductions of death or myocardial infarction. Patients >=80 years had half of the NNT and a third of the NNH of patients <60 years. Conclusions: In patients with NSTE-ACS, the relative reduction of death or non-fatal myocardial infarction with platelet glycoprotein IIb/IIIa receptor blockers was independent of patient age. Larger absolute outcome reductions were seen in older patients, but with a higher risk of major bleeding. Close monitoring of these patients is warranted.
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- 2007
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27. Effect of antecedent hypertension and follow-up blood pressure on outcomes after high-risk myocardial infarction
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Thune, J.J., Signorovitch, J., Velazquez, E.J., McMurray, J.J., Califf, R.M., Maggioni, A.P., Rouleau, J.L., Howlett, J., Zelenkofske, S., Pfeffer, M.A., Solomon, S.D., Køber, Lars Valeur, Thune, J.J., Signorovitch, J., Velazquez, E.J., McMurray, J.J., Califf, R.M., Maggioni, A.P., Rouleau, J.L., Howlett, J., Zelenkofske, S., Pfeffer, M.A., Solomon, S.D., and Køber, Lars Valeur
- Abstract
The influence of blood pressure on outcomes after high-risk myocardial infarction is not well characterized. We studied the relationship between blood pressure and the risk of cardiovascular events in 14 703 patients with heart failure, left ventricular systolic dysfunction, or both after acute myocardial infarction in the Valsartan in Myocardial Infarction Trial. We assessed the relationship between antecedent hypertension and outcomes and the association between elevated (systolic: >140 mm Hg) or low blood pressure (systolic: <100 mm Hg) in 2 of 3 follow-up visits during the first 6 months and subsequent cardiovascular events over a median 24.7 months of follow-up. Antecedent hypertension independently increased the risk of heart failure (hazard ratio [HR]: 1.19; 95% CI: 1.08 to 1.32), stroke (HR: 1.27; 95% CI: 1.02 to 1.58), cardiovascular death (HR: 1.11; 95% CI: 1.01 to 1.22), and the composite of death, myocardial infarction, heart failure, stroke, or cardiac arrest (HR: 1.13; 95% CI: 1.06 to 1.21). While low blood pressure in the postmyocardial infarction period was associated with increased risk of adverse events, patients with elevated blood pressure (n=1226) were at significantly higher risk of stroke (adjusted HR: 1.64; 95% CI: 1.17 to 2.29) and combined cardiovascular events (adjusted HR: 1.14; 95% CI: 1.00 to 1.31). Six months after a high-risk myocardial infarction, elevated systolic blood pressure, a potentially modifiable risk factor, is associated with an increased risk of subsequent stroke and cardiovascular events. Whether aggressive antihypertensive treatment can reduce this risk remains unknown Udgivelsesdato: 2008/1
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- 2007
28. Selection of reperfusion therapy for individual patients with evolving myocardial infarction
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Werf, F. van der, Vahanian, A., Gulba, D.C., Müller, J., Arnold, A.E.R., Bär, F., Vermeer, F., Verheugt, F.W.A., Boersma, H., Es, G.A. van, Deckers, J.W., Lenderink, T., Simoons, M.L., Steyerberg, E.W., Zwaan, C. van der, Boer, M.J. de, Zijlstra, F., Wilcox, R., Sleight, P., Selker, H.P., Califf, R.M., Granger, C., Lee, K.L., Ohman, M.E., Weaver, D.W., Love, T., White, H., and Collins, R.
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GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) - Abstract
Contains fulltext : 24867___.PDF (Publisher’s version ) (Open Access)
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- 1997
29. Creatine kinase-MB elevation after percutaneous coronary intervention predicts adverse outcomes in patients with acute coronary syndromes.
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Roe, M.T. (Matthew), Mahaffey, K.W. (Kenneth), Kilaru, R. (Rakhi), Akkerhuis, K.M. (Martijn), Simoons, M.L. (Maarten), Harrington, R.A. (Robert Alex), Tardiff, B.E. (Barbara), Granger, C.B. (Christopher), Ohman, E.M. (Magnus), Moliterno, D.J. (David), Lincoff, A.M. (Michael), Califf, R.M. (Robert), Topol, E.J. (Eric), Werf, F.J.J. (Frans) van de, Alexander, J.H.P. (John), Armstrong, P.W. (Paul), Roe, M.T. (Matthew), Mahaffey, K.W. (Kenneth), Kilaru, R. (Rakhi), Akkerhuis, K.M. (Martijn), Simoons, M.L. (Maarten), Harrington, R.A. (Robert Alex), Tardiff, B.E. (Barbara), Granger, C.B. (Christopher), Ohman, E.M. (Magnus), Moliterno, D.J. (David), Lincoff, A.M. (Michael), Califf, R.M. (Robert), Topol, E.J. (Eric), Werf, F.J.J. (Frans) van de, Alexander, J.H.P. (John), and Armstrong, P.W. (Paul)
- Abstract
AIM: To study the relationship between outcomes and peak creatine kinase (CK)-MB levels after percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary
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- 2004
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30. Effect of Nesiritide in Patients with Acute Decompensated Heart Failure
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O'Connor, C.M., primary, Starling, R.C., additional, Hernandez, A.F., additional, Armstrong, P.W., additional, Dickstein, K., additional, Hasselblad, V., additional, Heizer, G.M., additional, Komajda, M., additional, Massie, B.M., additional, McMurray, J.J.V., additional, Nieminen, M.S., additional, Reist, C.J., additional, Rouleau, J.L., additional, Swedberg, K., additional, Adams, K.F., additional, Anker, S.D., additional, Atar, D., additional, Battler, A., additional, Botero, R., additional, Bohidar, N.R., additional, Butler, J., additional, Clausell, N., additional, Corbalán, R., additional, Costanzo, M.R., additional, Dahlstrom, U., additional, Deckelbaum, L.I., additional, Diaz, R., additional, Dunlap, M.E., additional, Ezekowitz, J.A., additional, Feldman, D., additional, Felker, G.M., additional, Fonarow, G.C., additional, Gennevois, D., additional, Gottlieb, S.S., additional, Hill, J.A., additional, Hollander, J.E., additional, Howlett, J.G., additional, Hudson, M.P., additional, Kociol, R.D., additional, Krum, H., additional, Laucevicius, A., additional, Levy, W.C., additional, Méndez, G.F., additional, Metra, M., additional, Mittal, S., additional, Oh, B.-H., additional, Pereira, N.L., additional, Ponikowski, P., additional, Tang, W.H.W., additional, Tanomsup, S., additional, Teerlink, J.R., additional, Triposkiadis, F., additional, Troughton, R.W., additional, Voors, A.A., additional, Whellan, D.J., additional, Zannad, F., additional, and Califf, R.M., additional
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- 2011
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31. Frequency of stent thrombosis after acute coronary syndromes (from the SYMPHONY and 2nd SYMPHONY trials).
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Tolleson, T.R., Newby, L.K., Harrington, R.A., Bhapkar, M.V., Verheugt, F.W.A., Berger, P.B., Moliterno, D.J., White, H., Ohman, E.M., Werf, F. van de, Topol, E., Califf, R.M., Tolleson, T.R., Newby, L.K., Harrington, R.A., Bhapkar, M.V., Verheugt, F.W.A., Berger, P.B., Moliterno, D.J., White, H., Ohman, E.M., Werf, F. van de, Topol, E., and Califf, R.M.
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Item does not contain fulltext, We studied stent thrombosis in 4,607 patients with acute coronary syndromes who received a coronary stent as part of routine care during 2 trials of aspirin versus sibrafiban for secondary prevention. In these patients, stent thrombosis occurred more often than in previous patients who underwent elective percutaneous coronary intervention. These patients and their outcomes may be more representative of patients with typical acute coronary syndromes undergoing stenting in clinical practice.
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- 2003
32. Early statin initiation and outcomes in patients with acute coronary syndromes.
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Newby, L.K., Kristinsson, A., Weaver, W.D., Verheugt, F.W.A., Aylward, P., Dimas, A.P., Moliterno, D.J., McGuire, D.K., Bhapkar, M.V., Klein, W.W., Califf, R.M., Newby, L.K., Kristinsson, A., Weaver, W.D., Verheugt, F.W.A., Aylward, P., Dimas, A.P., Moliterno, D.J., McGuire, D.K., Bhapkar, M.V., Klein, W.W., and Califf, R.M.
- Abstract
Item does not contain fulltext, CONTEXT: The secondary prevention benefit of therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has been clearly demonstrated; however, the role of early initiation of statins after acute coronary syndromes (ACSs) is unknown. OBJECTIVE: To evaluate the association of early statin initiation (< or = 7 days) after ACS with 90-day and 1-year outcomes. DESIGN: Observational cohort from databases of 2 randomized clinical trials, SYMPHONY and 2nd SYMPHONY. SETTING: Nine hundred thirty-one clinical centers in 37 countries. PATIENTS: A total of 12,365 ACS patients randomized from August 1997 to August 1999 who were not taking statins prior to the index ACS and who either started statin therapy early (median, 2.0 [interquartile range, 1.0-3.1] days after ACS; n = 3952) or survived more than 5 days after ACS and never received statin therapy (n = 8413). MAIN OUTCOME MEASURES: Ninety-day incidence of death; death or myocardial infarction (MI); and death, MI, or severe recurrent ischemia; as well as 1-year incidence of death. RESULTS: Ninety-day and 1-year unadjusted mortality comparison suggested early statin benefit (1.2% for early statins vs 2.1% for no statins; hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.42-0.81 for 90-day comparisons and 2.3% for early statins vs 4.4% for no statins; HR, 0.52; 95% CI, 0.40-0.68 for 1-year comparison). However, no benefit was evident for 90-day death or MI (6.5% vs 6.9%; HR, 0.95; 95% CI, 0.82-1.11) or death, MI, or severe recurrent ischemia (9.2% vs 8.9%; HR, 1.04; 95% CI, 0.92-1.18). After propensity and covariate adjustment, there were no 90-day or 1-year differences between the early-statin group and the no-statin group. The 90-day adjusted HR for death was 1.08 (95% CI, 0.75-1.56); for death or MI, 1.08 (95% CI, 0.91-1.29); and for death, MI, or severe recurrent ischemia, 1.15 (95% CI, 0.99-1.34). One-year mortality-adjusted HR was 0.99 (95% CI, 0.73-1.33). Among 2711 patients with core labor
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- 2002
33. Characteristics, treatment and outcome of patients with non-ST-elevation acute coronary syndromes and multivessel coronary artery disease: observations from PURSUIT (Platelet Glycoprotein IIb/IIIa in unstable angina: receptor suppression using integreling therapy)
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Breeman, A. (Arno), Mercado, N.F. (Nestor), Lenzen, M.J. (Mattie), Harrington, R.A. (Robert Alex), Califf, R.M. (Robert), Topol, E.J. (Eric), Simoons, M.L. (Maarten), Brand, M.J.B.M. (Marcel) van den, Boersma, H. (Eric), Breeman, A. (Arno), Mercado, N.F. (Nestor), Lenzen, M.J. (Mattie), Harrington, R.A. (Robert Alex), Califf, R.M. (Robert), Topol, E.J. (Eric), Simoons, M.L. (Maarten), Brand, M.J.B.M. (Marcel) van den, and Boersma, H. (Eric)
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BACKGROUND: The 6-month clinical outcome of patients with multivessel disease enrolled in PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) is described. Patients with complete angiography data were included; multivessel disease was stratified according to the treatment strategy applied early during hospitalization, i.e. medical treatment, percutaneous coronary intervention (PCI) (balloon), PCI (stent), or coronary artery bypass grafting (CABG). METHODS: Patients were divided into three groups according to the treatment strategy applied during the first 30 days of enrolment. Patients who did not undergo a percutaneous or surgical coronary intervention were classified as medically treated. Patients who underwent a PCI (prior to a possible CABG) were separated from those who underwent a CABG (prior to a possible PCI). The PCI group was further subdivided: patients receiving >/=1 coronary stents were separated from those in whom no stents were used. RESULTS: The mortality rate at 30 days was 6.7, 3.9, 2.4 and 4.8% for the medical treatment, PCI (balloon), PCI (stent) and CABG groups, respectively (p value = 0.002). Differences as observed at 30 days were still present at 6-month follow-up with 11.1, 5.8, 5.5 and 6.5% mortality event rates for the aforementioned groups (p value = 0.002). The 30-day myocardial infarction (MI) rate according to the opinion of the Clinical Events Committee was lower among medically than non-medically treated patients, with the highest event rate observed in the CABG group (27.7%). Approximately half of the MIs in the PCI and CABG subgroups occurred within 48 h after the procedure. CONCLUSIONS: The observed differences in clinical outcomes are explained by an imbalance in baseline characteristics and comorbid conditions between the analyzed groups of patients.
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- 2002
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34. Sustained ventricular arrhythmias among patients with acute coronary syndromes with no ST-segment elevation: incidence, predictors, and outcomes
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White, H.D. (Harvey), Harrington, R.A. (Robert Alex), Simes, R.J. (John), Topol, E.J. (Eric), Moliterno, D.J. (David), Granger, C.B. (Christopher), Huang, Y. (Yao), Lee, K.L. (Kerry), Califf, R.M. (Robert), Simoons, M.L. (Maarten), Armstrong, P.W. (Paul), Werf, F.J.J. (Frans) van de, Al-Khatib, S.M. (Sana), White, H.D. (Harvey), Harrington, R.A. (Robert Alex), Simes, R.J. (John), Topol, E.J. (Eric), Moliterno, D.J. (David), Granger, C.B. (Christopher), Huang, Y. (Yao), Lee, K.L. (Kerry), Califf, R.M. (Robert), Simoons, M.L. (Maarten), Armstrong, P.W. (Paul), Werf, F.J.J. (Frans) van de, and Al-Khatib, S.M. (Sana)
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BACKGROUND: The prognosis of ventricular arrhythmias among patients with non-ST-elevation acute coronary syndromes is unknown. We studied the incidence, predictors, and outcomes of sustained ventricular arrhythmias in 4 large randomized trials of such patients. METHODS AND RESULTS: We pooled the datasets of the Global Use of Streptokinase and tPA for Occluded Arteries (GUSTO)-IIb, Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON)-A, and PARAGON-B trials (n=26 416). We identified independent predictors of ventricular fibrillation (VF) and ventricular tachycardia (VT) and compared the 30-day and 6-month mortality rates of patients who did (n=552) and did not (n=25 864) develop these arrhythmias during the index hospitalization. Independent predictors of in-hospital VF included prior hypertension, chronic obstructive pulmonary disease, prior myocardial infarction, and ST-segment changes at presentation. Except for hypertension, these variables also independently predicted in-hospital VT. In Cox proportional-hazards modeling, in-hospital VF and VT were independently associated with 30-day mortality (hazard ratio [HR], 23.2 [95% CI, 18.1 to 29.8] for VF and HR, 7.6 [95% CI, 5.5 to 10.4] for VT) and 6-month mortality (HR, 14.8 [95% CI, 12.1 to 18.3] for VF and HR, 5.0 [95% CI, 3.8 to 6.5] for VT). These differences remained significant after excluding patients with heart failure or cardiogenic shock and those who died <24 hours after enrollment. CONCLUSIONS: Despite the use of effective therapies for non-ST-elevation acute coronary syndromes, ventricular arrhythmias in this setting are associated with increased 30-day and 6-month mortality. More effective therapies are needed to improve the survival of patients with these arrhythmias.
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- 2002
35. Patients with acute coronary syndromes without persistent ST elevation undergoing percutaneous coronary intervention benefit most from early intervention with protection by a glycoprotein IIb/IIIa receptor blocker.
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Ronner, E. (Eelko), Boersma, H. (Eric), Akkerhuis, K.M. (Martijn), Harrington, R.A. (Robert Alex), Lincoff, A.M. (Michael), Deckers, J.W. (Jaap), Karsch, K. (Karl), Kleiman, N.S. (Neal), Vahanian, A.S. (Alec), Topol, E.J. (Eric), Califf, R.M. (Robert), Simoons, M.L. (Maarten), Ronner, E. (Eelko), Boersma, H. (Eric), Akkerhuis, K.M. (Martijn), Harrington, R.A. (Robert Alex), Lincoff, A.M. (Michael), Deckers, J.W. (Jaap), Karsch, K. (Karl), Kleiman, N.S. (Neal), Vahanian, A.S. (Alec), Topol, E.J. (Eric), Califf, R.M. (Robert), and Simoons, M.L. (Maarten)
- Abstract
BACKGROUND: Many patients with acute coronary syndromes are offered percutaneous coronary intervention. However, the appropriate indications for, and optimal timing of, such procedures are uncertain. We analysed timing of intervention and associated events (death and myocardial infarction) in the PURSUIT trial in which 9461 patients received a platelet glycoprotein IIb/IIIa inhibitor, eptifibatide, or placebo for 72 h. Other treatment was left to the investigators. 2430 patients underwent percutaneous coronary intervention within 30 days. Four groups were distinguished, who underwent percutaneous coronary intervention on day 1; on days 2 or 3; at 4 to 7 days; or between 8 until 30 days, for eptifibatide- and placebo-treated patients. RESULTS: The four groups treated with placebo demonstrated total 30-d
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- 2002
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36. Incidence and predictors of bleeding events after fibrinolytic therapy with fibrin-specific agents: a comparison of TNK-tPA and rt-PA.
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Werf, F. van de, Barron, H.V., Armstrong, P.W., Granger, C., Berioli, S., Barbash, G., Pehrsson, K., Verheugt, F.W.A., Meyer, J., Betriu, A., Califf, R.M., Li, X., Fox, N.L., Werf, F. van de, Barron, H.V., Armstrong, P.W., Granger, C., Berioli, S., Barbash, G., Pehrsson, K., Verheugt, F.W.A., Meyer, J., Betriu, A., Califf, R.M., Li, X., and Fox, N.L.
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Item does not contain fulltext, BACKGROUND: Fibrinolytic therapy increases the risk of bleeding events. TNK-tPA (tenecteplase) is a variant of rt-PA with greater fibrin specificity and reduced plasma clearance that can be given as a single bolus. We compared the incidence and predictors of bleeding events after treatment with TNK-tPA and rt-PA. METHODS AND RESULTS: In the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-2 trial, 16 949 patients with acute myocardial infarction were randomly assigned a single weight-adjusted bolus of TNK-tPA or a 90-min infusion of rt-PA. A total of 4.66% of patients in the TNK-tPA group experienced major non-cerebral bleeding, in comparison with 5.94% in the rt-PA group (P=0.0002). This lower rate was associated with a significant reduction in the need for blood transfusion (4.25% vs 5.49%, P=0.0003) and was consistent across subgroups. Independent risk factors for major bleeding were older age, female gender, lower body weight, enrolment in the U.S.A. and a diastolic blood pressure <70 mmHg. Females at high risk (age >75 years and body weight <67 kg) were less likely to have major bleeding when treated with TNK-tPA even after other risk factors were taken into account. A total of 0.93% of patients in the TNK-tPA and 0.94% of patients in the rt-PA group experienced an intracranial haemorrhage. Female patients >75 years of age who weighed <67 kg tended to have lower rates of intracranial haemorrhage when treated with TNK-tPA (3/264, 1.14% vs 8/265, 3.02%). CONCLUSIONS: The increased fibrin specificity and single bolus administration of TNK-tPA do not increase the risk of intracranial haemorrhage but are associated with less non-cerebral bleeding, especially amongst high-risk patients.
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- 2001
37. Disagreements between central clinical events committee and site investigator assessments of myocardial infarction end- points in an international clinical trial: Review of the PURSUIT study
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Mahaffey, K.W. (Kenneth), Harrington, R.A. (Robert Alex), Akkerhuis, K.M. (Martijn), Kleiman, N.S. (Neal), Berdan, L.G. (Lisa), Crenshaw, B.S. (Brian), Tardiff, B.E. (Barbara), Granger, C.B. (Christopher), DeJong, I. (Ingrid), Bhapkar, M. (Manju), Widimsky, P. (Petr), Corbalon, R. (Ramón), Lee, K.L. (Kerry), Deckers, J.W. (Jaap), Simoons, M.L. (Maarten), Topol, E.J. (Eric), Califf, R.M. (Robert), Mahaffey, K.W. (Kenneth), Harrington, R.A. (Robert Alex), Akkerhuis, K.M. (Martijn), Kleiman, N.S. (Neal), Berdan, L.G. (Lisa), Crenshaw, B.S. (Brian), Tardiff, B.E. (Barbara), Granger, C.B. (Christopher), DeJong, I. (Ingrid), Bhapkar, M. (Manju), Widimsky, P. (Petr), Corbalon, R. (Ramón), Lee, K.L. (Kerry), Deckers, J.W. (Jaap), Simoons, M.L. (Maarten), Topol, E.J. (Eric), and Califf, R.M. (Robert)
- Abstract
Background. Limited information has been published regarding how specific processes for event adjudication can affect event rates in trials. We reviewed nonfatal myocardial infarctions (MIs) reported by site investigators in the international Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial and those adjudicated by a central clinical events committee (CEC) to determine the reasons for differences in event rates. Methods. The PURSUIT trial randomised 10,948 patients with acute coronary syndromes to receive eptifibatide or placebo. The primary end-point was death or post-enrolment MI at 30 days as assessed by the CEC; this end-point was also constructed using site-reported events. The CEC identified suspected MIs by systematic review of clinical, cardiac enzyme, and electrocardiographic data. Results. The CEC identified 5005 (46%) suspected events, of which 1415 (28%) were adjudicated as MI. The site investigator and CEC assessments of whether a MI had occurred disagreed in 983 (20%) of the 5005 patients with suspected MI, mostly reflecting site misclassification of post-enrolment MIs (as enrolment MIs) or underreported periprocedural MIs. Patients for whom the CEC and site investigator agreed that no end-point MI had occurred had the lowest mortality at 30 days and between 30 days and 6 months, and those with agreement that a MI had occurred had the highest mortality. Conclusion. CEC adjudication provides a standard, systematic, independent, and unbiased assessment of end-points, particularly for trials that span geographic regions and clinical practice settings. Understanding the review process
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- 2001
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38. Risk of stroke associated with abciximab among patients undergoing percutaneous coronary intervention
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Akkerhuis, K.M. (Martijn), Lincoff, A.M. (Michael), Tcheng, J.E. (James), Anderson, K. (Keaven), Balog, C., Califf, R.M. (Robert), Topol, E.J. (Eric), Simoons, M.L. (Maarten), Deckers, J.W. (Jaap), Boersma, H. (Eric), Akkerhuis, K.M. (Martijn), Lincoff, A.M. (Michael), Tcheng, J.E. (James), Anderson, K. (Keaven), Balog, C., Califf, R.M. (Robert), Topol, E.J. (Eric), Simoons, M.L. (Maarten), Deckers, J.W. (Jaap), and Boersma, H. (Eric)
- Abstract
CONTEXT: Abciximab, a potent inhibitor of the platelet glycoprotein IIb/IIIa receptor, reduces thrombotic complications in patients undergoing percutaneous coronary interv
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- 2001
39. Systematic adjudication of myocardial infarction end-points in an international clinical trial.
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Mahaffey, K.W. (Kenneth), Harrington, R.A. (Robert Alex), Kleiman, N.S. (Neal), Berdan, L.G. (Lisa), Crenshaw, B.S. (Brian), Tardiff, B.E. (Barbara), Granger, C.B. (Christopher), DeJong, I. (Ingrid), Bhapkar, M. (Manju), Widimsky, P. (Petr), Corbalon, R. (Ramón), Lee, K.L. (Kerry), Deckers, J.W. (Jaap), Simoons, M.L. (Maarten), Topol, E.J. (Eric), Califf, R.M. (Robert), Akkerhuis, K.M. (Martijn), Mahaffey, K.W. (Kenneth), Harrington, R.A. (Robert Alex), Kleiman, N.S. (Neal), Berdan, L.G. (Lisa), Crenshaw, B.S. (Brian), Tardiff, B.E. (Barbara), Granger, C.B. (Christopher), DeJong, I. (Ingrid), Bhapkar, M. (Manju), Widimsky, P. (Petr), Corbalon, R. (Ramón), Lee, K.L. (Kerry), Deckers, J.W. (Jaap), Simoons, M.L. (Maarten), Topol, E.J. (Eric), Califf, R.M. (Robert), and Akkerhuis, K.M. (Martijn)
- Abstract
BACKGROUND: Clinical events committees (CEC) are used routinely to adjudicate suspected end-points in cardiovascular trials, but little information has been published about the various processes used. We reviewed results of the CEC process used to identify and adjudicate suspected end-point (post-enrolment) myocardial infarction (MI) in the large Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial. METHODS: The PURSUIT trial randomised 10,948 patients with acute coronary syndromes to receive eptifibatide or placebo. A central adjudication process was established prospectively to identify all suspected MIs and adjudicate events based on protocol definitions of MI. Suspected MIs were identified by systematic review of data collection forms, cardiac enzyme results, and electrocardiograms. Two physicians independently reviewed all suspected events. If they disagreed whether a MI had occurred, a committee of cardiologists adjudicated the case. RESULTS: The CEC identified 5005 patients with suspected infarction (46%), of which 1415 (28%) were adjudicated
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- 2001
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40. Lack of progress in cardiogenic shock: Lessons from the GUSTO trials
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Menon, Venu, Hochman, J.S., Stebbins, A., Pfisterer, M., Col, J., Anderson, R.D., Hasdai, D., Holmes Jr., D.R., Bates, E.R., Topol, E.J., Califf, R.M., Ohman, E.M., Menon, Venu, Hochman, J.S., Stebbins, A., Pfisterer, M., Col, J., Anderson, R.D., Hasdai, D., Holmes Jr., D.R., Bates, E.R., Topol, E.J., Califf, R.M., and Ohman, E.M.
- Abstract
Aims: We used the GUSTO-I and GUSTO-III databases to evaluate our performance in treating cardiogenic shock patients over much of the 1990s. Methods and Results: GUSTO-I (1990-1993) and GUSTO-III (1995-1997) prospectively identified all patients with cardiogenic shock complicating acute myocardial infarction. Demographics, clinical presentation and outcomes for cardiogenic shock patients in the two trials were compared. Only patients enrolled with cardiogenic shock in countries common to both trials were included in these analysis. The 695 patients with cardiogenic shock in GUSTO-III were compared with the 2814 patients with cardiogenic shock in GUSTO-I. GUSTO-III patients were older (P=0.0001) and more likely to be diabetic (P=0.009) and hypertensive (P=0.025). They had a higher Killip class (P=0.002) and significantly greater index anterior infarction than cardiogenic shock patients enrolled in GUSTO-I. Time to treatment, presentation heart rate, and diastolic blood pressure were similar; however, systolic blood pressure at presentation was higher among GUSTO-III patients (P=0.002). Rates of coronary angiography, pulmonary artery catheterization, and mechanical ventilation declined in GUSTO-III compared with GUSTO-I (P=0.001); rates of angioplasty and bypass surgery were similar. Cardiogenic shock mortality in GUSTO-III was significantly higher than in GUSTO-I (62 vs 54%, P=0.001), as were rates of reinfarction (14 vs 11%, P=0.013) and recurrent ischaemia (35 vs 27%, P=0.00001). Mortality at non-U.S. sites (68 and 64%) was higher than at U.S. sites (53 and 50%) in both GUSTO-I and GUSTO-III studies, respectively. Angioplasty, bypass surgery, and balloon pump rates were lower for non-U.S. patients. Conclusions: Cardiogenic shock continues to be associated with high mortality in thrombolytic-treated patients. Lower mortality observed in the U.S.A. supports consideration for percutaneous and surgical revascularization. (C) 2000 The European Society of Cardiology.
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- 2000
41. Association between minor elevations of creatine kinase-MB level and mortality in patients with acute coronary syndromes without ST-segment elevation.
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Alexander, J.H.P. (John), Chierchia, S.L., Boland, J.B. (Jean), Harrington, R.A. (Robert Alex), Simoons, M.L. (Maarten), Topol, E.J. (Eric), Califf, R.M. (Robert), Sparapani, R.A., Mahaffey, K.W. (Kenneth), Newby, L.K. (Kristin), Ohman, E.M. (Magnus), Corbalan, R., Deckers, J.W. (Jaap), Alexander, J.H.P. (John), Chierchia, S.L., Boland, J.B. (Jean), Harrington, R.A. (Robert Alex), Simoons, M.L. (Maarten), Topol, E.J. (Eric), Califf, R.M. (Robert), Sparapani, R.A., Mahaffey, K.W. (Kenneth), Newby, L.K. (Kristin), Ohman, E.M. (Magnus), Corbalan, R., and Deckers, J.W. (Jaap)
- Abstract
CONTEXT: Controversy surrounds the diagnostic and prognostic importance of slightly elevated cardiac markers in patients with acute coronary syndromes without ST-segment elevation. OBJECTIVES: To investigate the relationship between peak creatine kinase (CK)-MB level and outcome and to determine whether a threshold CK-MB level exists below which risk is not increased. DESIGN AND SETTING: Retrospective observational analysis of data from the international Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, conducted from November 1995 to January 1997. PATIENTS: A total of 8250 patients with acute coronary syndromes without ST-segment elevation who had at least 1 CK-MB sample collected during their index hospitalization. MAIN OUTCOME MEASURE: Mortality at 30 days and 6 months, was assessed by category of index-hospitalization peak CK-MB level (0-1, >1-2, >2-3, >3-5, >5-10, or >10 times the upper limit of normal). Multivariable logistic regression was used to determine the independent prognostic significance of peak CK-MB level after adjustment for baseline predictors of 30-day and 6-month mortality. RESULTS: Mortality at 30 days and 6 months increased from 1.8% and 4.0%, respectively, in patients with normal peak CK-MB levels, to 3.3% and 6.2 % at peak CK-MB levels 1 to 2 times normal, to 5.1% and 7.5% at peak CK-MB levels 3 to 5 times normal, and to 8.3% and 11.0% at peak CK-MB levels greater than 10 times normal. Log-transformed peak CK-MB levels were predictive of adjusted 30-day and 6-month mortality (P<.001 for both). CONCLUSIONS: Our data show that elevation of CK-MB level is strongly related to mortality in patients with acute coronary syndromes without ST-segment elevation, and that the increased risk begins with CK-MB levels just above normal. In the appropriate clinical context, even minor CK-MB elevations should be considered indicative of myocardial infarction.
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- 2000
42. Early percutaneous coronary intervention, platelet inhibition with eptifibatide, and clinical outcomes in patients with acute coronary syndromes. PURSUIT Investigators
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Kleiman, N.S. (Neal), Cokkinos, D.V. (Dennis), Simoons, M.L. (Maarten), Harrington, R.A. (Robert Alex), Califf, R.M. (Robert), Topol, E.J. (Eric), Lincoff, A.M. (Michael), Flaker, G.C., Pieper, K.S. (Karen), Wilcox, R.G. (Robert), Berdan, L.G. (Lisa), Lorenz, T.J., Boersma, H. (Eric), Kleiman, N.S. (Neal), Cokkinos, D.V. (Dennis), Simoons, M.L. (Maarten), Harrington, R.A. (Robert Alex), Califf, R.M. (Robert), Topol, E.J. (Eric), Lincoff, A.M. (Michael), Flaker, G.C., Pieper, K.S. (Karen), Wilcox, R.G. (Robert), Berdan, L.G. (Lisa), Lorenz, T.J., and Boersma, H. (Eric)
- Abstract
BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa antagonists prevent the composite end point of death or myocardial infarction (MI) in patients with acute coronary syndromes. There is uncertainty about whether this effect is confined to patients who have percutaneous coronary interventions (PCIs) and whether PCIs further prevent death or MI in patients already treated with GP IIb/IIIa antagonists. METHODS AND RESULTS: PURSUIT patients were treated with the GP IIb/IIIa antagonist eptifibatide or placebo; PCIs were performed according to physician practices. In 2253 of 9641 patients (23.4%), PCI was performed by 30 days. Early (<72 hours) PCI was performed in 1228 (12.7%). In 34 placebo patients (5.5%) and 10 treated with eptifibatide (1.7%) (P=0.001), MI preceded early PCI. In patients censored for PCI across the 30-day period, there was a significant reduction in the primary composite end point in eptifibatide patients (P=0.035). Eptifibatide reduced 30-day events in patients who had early PCI (11.6% versus 16.7%, P=0.01) and in patients who did not (14.6% versus 15.6%, P=0.23). After adjustment for PCI propensity, there was no evidence that eptifibatide treatment effect differed between patients with or without early PCI (P for interaction=0.634). PCI was not associated with a reduction of the primary composite end point but was associated with a reduced (nonspecified) composite of death or Q-wave MI. This association disappeared after adjustment for propensity for early PCI. CONCLUSIONS: Eptifibatide reduced the composite rates of death or MI in PCI patients and those managed conservatively.
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- 2000
43. Clinical and therapeutic profile of patients presenting with acute coronary syndromes who do not have significant coronary artery disease.The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial Investigators
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Roe, M.T. (Matthew), Vahanian, A.S. (Alec), Harrington, R.A. (Robert Alex), Prosper, D.M., Pieper, K.S. (Karen), Topol, E.J. (Eric), Bhatt, D.L. (Deepak), Lincoff, A.M. (Michael), Simoons, M.L. (Maarten), Califf, R.M. (Robert), Ohman, E.M. (Magnus), Karsch, K. (Karl), Kitt, M.M. (Michael), Ruzyllo, W. (Witold), Akkerhuis, K.M. (Martijn), Roe, M.T. (Matthew), Vahanian, A.S. (Alec), Harrington, R.A. (Robert Alex), Prosper, D.M., Pieper, K.S. (Karen), Topol, E.J. (Eric), Bhatt, D.L. (Deepak), Lincoff, A.M. (Michael), Simoons, M.L. (Maarten), Califf, R.M. (Robert), Ohman, E.M. (Magnus), Karsch, K. (Karl), Kitt, M.M. (Michael), Ruzyllo, W. (Witold), and Akkerhuis, K.M. (Martijn)
- Abstract
BACKGROUND: A proportion of patients who present with suspected acute coronary syndrome (ACS) are found to have insignificant coronary artery disease (CAD) during coronary angiography, but these patients have not been well characterized. METHODS AND RESULTS: Of the 5767 patients with non-ST-segment elevation ACS who were enrolled in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial and who underwent in-hospital angiography, 88% had significant CAD (any stenosis >50%), 6% had mild CAD (any stenosis >0% to =50%), and 6% had no CAD (no stenosis identified). The frequency of death or nonfatal myocardial infarction at 30 days was reduced with eptifibatide treatment in patients with significant CAD (18.3% versus 15.6% for placebo, P=0.006) but not in those with mild CAD (6.6% versus 5.4%, P=0.62) and with no CAD (3.0% versus 1. 2%, P=0.28). We identified independent baseline predictors of insignificant CAD (mild or no CAD) and used them to develop a simple predictive nomogram of the probability of insignificant CAD for use at hospital presentation. This nomogram was validated in a separate population of patients with non-ST-segment elevation ACS. CONCLUSIONS: Patients with suspected ACS found to have insignificant CAD have a low risk of adverse outcomes, do not appear to benefit from treatment with eptifibatide, and can be predicted with a simple nomogram drawn from baseline characteristics. Because patients with significant CAD appear to have an enhanced benefit from eptifibatide treatment, the predictive nomogram developed can be used to determine indications for glycoprotein IIb/IIIa blockade.
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- 2000
44. Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators
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Chang, W.C., Lee, K.L. (Kerry), Akkerhuis, K.M. (Martijn), Simoons, M.L. (Maarten), Harrington, R.A. (Robert Alex), Topol, E.J. (Eric), Armstrong, P.W. (Paul), Califf, R.M. (Robert), Lincoff, A.M. (Michael), Pieper, K.S. (Karen), Steyerberg, E.W. (Ewout), Wilcox, R.G. (Robert), Deckers, J.W. (Jaap), Boersma, H. (Eric), Chang, W.C., Lee, K.L. (Kerry), Akkerhuis, K.M. (Martijn), Simoons, M.L. (Maarten), Harrington, R.A. (Robert Alex), Topol, E.J. (Eric), Armstrong, P.W. (Paul), Califf, R.M. (Robert), Lincoff, A.M. (Michael), Pieper, K.S. (Karen), Steyerberg, E.W. (Ewout), Wilcox, R.G. (Robert), Deckers, J.W. (Jaap), and Boersma, H. (Eric)
- Abstract
BACKGROUND: Appropriate treatment policies should include an accurate estimate of a patient's baseline risk. Risk modeling to date has been underutilized in patients with acute coronary syndromes without persistent ST-segment elevation. METHODS AND RESULTS: We analyzed the relation between baseline characteristics and the 30-day incidence of death and the composite of death or myocardial (re)infarction in 9461 patients with acute coronary syndromes without persistent ST-segment elevation enrolled in the PURSUIT trial [Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (eptifibatide) Therapy]. Variables examined included demographics, history, hemodynamic condition, and symptom duration. Risk models were created with multivariable logistic regression and validated by bootstrapping techniques. There was a 3.6% mortality rate and 11.4% infarction rate by 30 days. More than 20 significant predictors for mortality and for the composite end point were identified. The most important baseline determinants of death were age (adjusted chi(2)=95), heart rate (chi(2)=32), systolic blood pressure (chi(2)=20), ST-segment depression (chi(2)=20), signs of heart failure (chi(2)=18), and cardiac enzymes (chi(2)=15). Determinants of mortality were generally also predictive of death or myocardial (re)infarction. Differences were observed, however, in the relative prognostic importance of predictive variables for mortality alone or the composite end point; for example, sex was a more important determinant of the composite end point (chi(2)=21) than of death alone (chi(2)=10). The accuracy of the prediction of the composite end point was less than that of mortality (C-index 0.67 versus 0.81). CONCLUSIONS: The occurrence of adverse events after presentation with acute coronary syndromes is affected by multiple factors. These factors should be considered in the clinical decision-making process.
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- 2000
45. Stroke in Patients With Acute Coronary Syndromes: Incidence and Outcomes in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial
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Mahaffey, K.W. (Kenneth), MacAulay, C.M., Harrington, R.A. (Robert Alex), Simoons, M.L. (Maarten), Granger, C.B. (Christopher), Califf, R.M. (Robert), Graffagnino, C. (Carmen), Alberts, M.J., Laskowitz, D.T., Topol, E.J. (Eric), Miller, J.M., Sloan, M.A. (Michael), Berdan, L.G. (Lisa), Lincoff, A.M. (Michael), Deckers, J.W. (Jaap), Mahaffey, K.W. (Kenneth), MacAulay, C.M., Harrington, R.A. (Robert Alex), Simoons, M.L. (Maarten), Granger, C.B. (Christopher), Califf, R.M. (Robert), Graffagnino, C. (Carmen), Alberts, M.J., Laskowitz, D.T., Topol, E.J. (Eric), Miller, J.M., Sloan, M.A. (Michael), Berdan, L.G. (Lisa), Lincoff, A.M. (Michael), and Deckers, J.W. (Jaap)
- Abstract
BACKGROUND: The incidence of stroke in patients with acute coronary syndromes has not been clearly defined because few trials in this patient population have been large enough to provide stable estimates of stroke rates. METHODS AND RESULTS: We studied the 10 948 patients with acute coronary syndromes without persistent ST-segment elevation who were randomly assigned to placebo or the platelet glycoprotein IIb/IIIa receptor inhibitor eptifibatide in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial to determine stroke rates, stroke types, clinical outcomes in patients with stroke, and independent baseline clinical predictors for nonhemorrhagic stroke. Stroke occurred in 79 (0.7%) patients, with 66 (0.6%) nonhemorrhagic, 6 intracranial hemorrhages, 3 cerebral infarctions with hemorrhagic conversion, and 4 of uncertain cause. There were no differences in stroke rates between patients who received placebo and those assigned high-dose eptifibatide (odds ratios and 95% confidence intervals 0.82 [0.59, 1.14] and 0.70 [0.49, 0.99], respectively). Of the 79 patients with stroke, 17 (22%) died within 30 days, and another 26 (32%) were disabled by hospital discharge or 30 days, whichever came first. Higher heart rate was the most important baseline clinical predictor of nonhemorrhagic stroke, followed by older age, prior anterior myocardial infarction, prior stroke or transient ischemic attack, and diabetes mellitus. These factors were used to develop a simple scoring nomogram that can predict the risk of nonhemorrhagic stroke. CONCLUSIONS: Strok
- Published
- 1999
46. Effects of stroke on medical resource use and costs in acute myocardial infarction. GUSTO I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Study
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Tung, C.Y., White, H.D. (Harvey), Clapp-Channing, N., Mark, D.B. (Daniel), Simoons, M.L. (Maarten), Califf, R.M. (Robert), Gore, J.M. (Joel), Granger, C.B. (Christopher), Sloan, M.A. (Michael), Topol, E.J. (Eric), Knight, J.D. (David), Weaver, W.D., Mahaffey, K.W. (Kenneth), Tung, C.Y., White, H.D. (Harvey), Clapp-Channing, N., Mark, D.B. (Daniel), Simoons, M.L. (Maarten), Califf, R.M. (Robert), Gore, J.M. (Joel), Granger, C.B. (Christopher), Sloan, M.A. (Michael), Topol, E.J. (Eric), Knight, J.D. (David), Weaver, W.D., and Mahaffey, K.W. (Kenneth)
- Abstract
BACKGROUND: Stroke occurs concurrently with myocardial infarction (MI) in approximately 30 000 US patients each year. This number is expected to rise with the increasing use of thrombolytic therapy for MI. However, no data exist for the economic effect of stroke in the setting of acute MI (AMI). The purpose of this prospective study was to assess the effect of stroke on medical resource use and costs in AMI patients in the United States. METHODS AND RESULTS: Medical resource use and cost data were prospectively collected for 2566 randomly selected US GUSTO I patients (from 23 105 patients) and for the 321 US GUSTO I patients who developed non-bypass surgery-related stroke during the baseline hospitalization. Follow-up was for 1 year. All costs are expressed in 1993 US dollars. During the baseline hospitalization, stroke was associated with a reduction in cardiac procedure rates and an increase in length of stay, despite a hospital mortality rate of 37%. Together with stroke-related procedural costs of $2220 per patient, the baseline medical costs increased by 44% ($29 242 versus $20 301, P<0.0001). Follow-up medical costs were substantially higher for stroke survivors ($22 400 versus $5282, P<0.0001), dominated by the cost of institutional care. The main determinant for institutional care was discharge disability status. The cumulative 1-year medical costs for stroke patients were $15 092 higher than for no-stroke patients. Hemorrhagic stroke patients had a much higher hospital mortality rate than non-hemorrhagic stroke patients (53% versus 15%, P<0.001), which was associated with approximately $7200 lower mean baseline hospitaliz
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- 1999
47. Platelet Glycoprotein IIb/IIIa Receptor Inhibition in Non-ST-Elevation Acute Coronary Syndromes
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Akkerhuis, K.M. (Martijn), Théroux, P. (Pierre), Califf, R.M. (Robert), Topol, E.J. (Eric), Simoons, M.L. (Maarten), Boersma, H. (Eric), Akkerhuis, K.M. (Martijn), Théroux, P. (Pierre), Califf, R.M. (Robert), Topol, E.J. (Eric), Simoons, M.L. (Maarten), and Boersma, H. (Eric)
- Abstract
BACKGROUND: Glycoprotein (GP) IIb/IIIa receptor blockers prevent life-threatening cardiac complications in patients with acute coronary syndromes without ST-segment elevation and protect against thrombotic complications associated with percutaneous coronary interventions (PCIs). The question arises as to whether these 2 beneficial effects are independent and additive. METHODS AND RESULTS: We analyzed data from the CAPTURE, PURSUIT, and PRISM-PLUS randomized trials, which studied the effects of the GP IIb/IIIa inhibitors abciximab, eptifibatide, and tirofiban, respectively, in acute coronary syndrome patients without persistent ST-segment elevation, with a period of study drug infusion before a possible PCI. During the period of pharmacological treatment, each trial demonstrated a significant reduction in the rate of death or nonfatal myocardial infarction in patients randomized to the GP IIb/IIIa inhibitor compared with placebo. The 3 trials combined showed a 2.5% event rate in this period in the GP IIb/IIIa inhibitor group (N=6125) versus 3.8% in placebo (N=6171), which implies a 34% relative reduction (P<0.001). During study medication, a PCI was performed in 1358 patients assigned GP IIb/IIIa inhibition and 1396 placebo patients. The event rate during the first 48 hours after PCI was also significantly lower in the GP IIb/IIIa inhibitor group (4. 9% versus 8.0%; 41% reduction; P<0.001). No further benefit or rebound effect was observed beyond 48 hours after the PCI. CONCLUSIONS: There is conclusive evidence of an early benefit of GP IIb/IIIa inhibitors during medical treatment in patients with acute coronary syndromes without persistent ST-segment elevation. In addition, in patients subsequently undergoing PCI, GP IIb/IIIa inhibition protects against myocardial damage associated with the intervention.
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- 1999
48. Patients with Evolving Myocardial Infarction Have a Significant Missed Opportunity for Earlier Treatment: Experience from the SYNERGY Trial
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Miller, C.D., primary, Kontos, M., additional, Mahaffey, K.W., additional, Fermann, G.J., additional, Banerjee, A., additional, Pollack, C.V., additional, Santos, R., additional, Ferguson, J.J., additional, Califf, R.M., additional, and Hoekstra, J.W., additional
- Published
- 2005
- Full Text
- View/download PDF
49. Risk Factors for In-hospital Nonhemorrhagic Stroke in Patients With Acute Myocardial Infarction Treated With Thrombolysis: Results from GUSTO-I
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Mahaffey, K.W. (Kenneth), Califf, R.M. (Robert), Granger, C.B. (Christopher), Sloan, M.A. (Michael), Thompson, T.D. (Trevor), Gore, J.M. (Joel), Weaver, W.D., White, H.D. (Harvey), Simoons, M.L. (Maarten), Barbash, G.I., Topol, E.J. (Eric), Mahaffey, K.W. (Kenneth), Califf, R.M. (Robert), Granger, C.B. (Christopher), Sloan, M.A. (Michael), Thompson, T.D. (Trevor), Gore, J.M. (Joel), Weaver, W.D., White, H.D. (Harvey), Simoons, M.L. (Maarten), Barbash, G.I., and Topol, E.J. (Eric)
- Abstract
BACKGROUND: Nonhemorrhagic stroke occurs in 0.1% to 1.3% of patients with acute myocardial infarction who are treated with thrombolysis, with substantial associated mortality and morbidity. Little is known about the risk factors for its occurrence. METHODS AND RESULTS: We studied the 247 patients with nonhemorrhagic stroke who were randomly assigned to one of four thrombolytic regimens within 6 hours of symptom onset in the GUSTO-I trial. We assessed the univariable and multivariable baseline risk factors for nonhemorrhagic stroke and created a scoring nomogram from the baseline multivariable modeling. We used time-dependent Cox modeling to determine multivariable in-hospital predictors of nonhemorrhagic stroke. Baseline and in-hospital predictors were then combined to determine the overall predictors of nonhemorrhagic stroke. Of the 247 patients, 42 (17%) died and another 98 (40%) were disabled by 30-day follow-up. Older age was the most important baseline clinical predictor of nonhemorrhagic stroke, followed by higher heart rate, history of stroke or transient ischemic attack, diabetes, previous angina, and history of hypertension. These factors remained statistically significant predictors in the combined model, along with worse Killip class, coronary angiography, bypass surgery, and atrial fibrillation/flutter. CONCLUSIONS: Nonhemorrhagic stroke is a serious event in patients with acute myocardial infarction who are treated with thrombolytic, antithrombin, and antiplatelet therapy. We developed a simple nomogram that can predict the risk of nonhemorrhagic stroke on the basis of baseline clinical characteristics. Prophylactic anticoagulation may be an important treatment strategy for patients with high probability for nonhemorrhagic stroke, but further study is needed.
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- 1998
50. Selection of thrombolytic therapy for individual patients: development of a clinical model
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Califf, R.M. (Robert), Woodlief, L.H. (Lynn), Harrell, F.E. (Frank), Lee, K.L. (Kerry), White, H.D. (Harvey), Guerci, A.D. (Alan), Barbash, G.I., Simes, R.J. (John), Weaver, W.D., Simoons, M.L. (Maarten), Topol, E.J. (Eric), Califf, R.M. (Robert), Woodlief, L.H. (Lynn), Harrell, F.E. (Frank), Lee, K.L. (Kerry), White, H.D. (Harvey), Guerci, A.D. (Alan), Barbash, G.I., Simes, R.J. (John), Weaver, W.D., Simoons, M.L. (Maarten), and Topol, E.J. (Eric)
- Abstract
We developed a logistic regression model with data from the GUSTO-I trial to predict mortality rate differences in individual patients who received accelerated tissue plasminogen activator (TPA) versus streptokinase treatment for acute myocardial infarction. A nomogram was developed from a reduced version of this model that approximated the underlying risk of patients treated with streptokinase, and thus the benefit of TPA. The 30-day mortality rate with accelerated TPA was 0.063 versus 0.073 with streptokinase and subcutaneously administered heparin and 0.074 with streptokinase and intravenously administered heparin. No baseline patient characteristics were significantly associated with a different relative effect of TPA. Older patients and those with anterior infarction, higher Killip classification (except Killip class IV), lower blood pressure, and increased heart rate had the greatest absolute benefit with accelerated TPA. Patients with acute myocardial infarction who had more high-risk characteristics derived a greater absolute benefit from treatment with accelerated TPA versus streptokinase.
- Published
- 1997
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