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2. Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease
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Lincoff, A. Michael, Nicholls, Stephen J., Riesmeyer, Jeffrey S., Barter, Philip J., Brewer, H. Bryan, Fox, Keith A. A., Gibson, C. Michael, Granger, Christopher, Menon, Venu, Montalescot, Gilles, Rader, Daniel, Tall, Alan R., McErlean, Ellen, Wolski, Kathy, Ruotolo, Giacomo, Vangerow, Burkhard, Weerakkody, Govinda, Goodman, Shaun G., Conde, Diego, McGuire, Darren K., Nicolau, Jose C., Leiva-Pons, Jose L., Pesant, Yves, Li, Weimin, Kandath, David, Kouz, Simon, Tahirkheli, Naeem, Mason, Denise, Nissen, Steven E. Del Valle M, Finnell JB, Standley J, Poi K, Croaning J, Tong YC, Guerra JL, Guasparini G, Hubert C, Ardissino D, Betteridge J, Borghi C, Bruckert E, Chiang CE, Cinteza M, Dalby AJ, Erlinge D, Fernandez-Ortiz A, Ge J, Gottlieb S, Goudev A, Gratsiansky N, Huber K, Ilavská A, Jeong MH, Jukema JW, Katus H, Keltai M, Krum H, Nielsen H, Ogawa H, Ongen Z, Parkhomenko A, Raugaliene R, Renkin J, Rynkiewicz A, Steinhubl S, White H, Widimsky P, Zhu J, Armstrong P, Ridker P, Mahaffey K, Steg G, Wittes J, Bhargava A, Chenier M, Coleman C, Cremer P, Jellis C, Lahoud R, Lappe J, Min D, Monteleone P, Newton D, Stegman B, Senn T, Katzan I, Sharma J, Uchino K, Vora N, Brown K, Fabec D, Piper P, Preston S, Colombo T, Pagel-Langenickel I, Penev P, Maixing A, Crowley K, Sarkar S, Torosyan N, Castano L, Tran D, Dena V, Blain L, Keenan G, Slade K, Quinlan E, Edwards R, Ren H, Glenny J, Maffei L, Albisu Di Gennaro J, Caccavo A, Prado A, Colombo H, Luquez H, Lobo Marquez L, Hammett C, Blombery P, Colquhoun D, Amerena J, Howes L, Cooke D, Simpson R, Horowitz J, Sullivan D, Proietto J, Yeo W, Hirschl M, Hanusch U, Drexel H, Brodmann M, Wollaert B, De Wolf L, Delforge M, Vanwelden J, Peeters A, Siqueira Bodart J, Montenegro R, Franken M, Eliaschewitz F, Parvanova Z, Raev D, Mincheva V, Kichukov K, Stoyanov M, Apostolova E, Tzekova M, Dimov B, Lazov P, Devedzhiev T, Dion D, Poirier P, Lavoie JP, Lonn E, Shukla D, Chehayeb R, Nault P, Gaudet D, Tardif JC, Beaudry Y, Bakbak A, Wong B, St-Maurice F, Labonte R, Polasek P, Sweet M, Bhargava R, Nawaz S, Pandey S, Tishler S, Peterson S, O’Keefe D, Genest J, Syan R, Leiter L, Li H, Ma W, Ma C, Xu D, Li X, Hala T, Machova V, Smejkalova O, Vodnansky P, Reichert P, Velimsky T, Matuska J, Machkova M, Jerabek O, Kuchar J, Rasmussen T, Lindgren L, Alexandersen P, Bang L, Brønnum-Schou J, Valter I, Soots M, Lanno R, Rosenthal S, Cottin Y, Elbaz M, Lafitte S, Silvain J, Coste P, Rangé G, Gosse P, Morel O, Berrouschot J, Bourhaial H, Toursarkissian N, Appel KF, Rieker W, Stellbrink C, Münzel T, Geisler T, Kadel C, Giannitsis E, Trenk D, vom Dahl J, Dorsel T, Singer O, Schäufele T, Natour M, Ozaki R, Lau E, Chan K, Yeung V, Yu C, Lakatos F, Zólyomi S, Vangel S, Merkely B, Szakal I, Sipos A, Laszloczky A, Kis E, Szocs A, Szántai G, Faludi P, Kancz S, Oroszlan T, Hamoud S, Francis A, Chorin E, Leibowitz D, Kracoff O, Weisz G, Schiff E, Bitzur R, Hussein O, Di Lorenzo L, Visona A, Mos L, De Luca G, Salvioni A, Rubba P, Imberti D, Bucci M, Saku K, Sueyoshi A, Ohshima K, Kazatani Y, Shimizu M, Fujii K, Higa N, Kawamitsu K, Shimomura H, Hoshizaki H, Tashiro H, Baden M, Ueda O, Tanabe J, Momiyama Y, Hosokawa S, Takahashi N, Kimura K, Fujinaga H, Masutani M, Kuramochi T, Higashikata T, Ichikawa S, Yamagishi M, Sakota S, Sakuragi S, Suzuki M, Taguchi S, Nakamura T, Ozaki Y, Tsujita K, Yasuda S, Ando K, Fujimoto K, Tanabe K, Fukunaga M, Kavaliauskiene R, Motiejuniene L, Slapikas R, Jarasuniene D, De los Rios Ibarra M, Alcocer Gamba M, Nevarez Ruiz L, Fajardo-Campos P, Llamas Esperon G, Violante Ortiz R, Stobschinski de Alba C, Guizar Sanchez C, Guerra Lopez A, Montano E, Miracle S, Fanghanel G, Lenderink T, Troquay R, Van Leendert R, van Eck J, Hamer B, Ronner E, Karalis I, Lok D, Magro M, Westendorp I, Stroes E, De Melker E, Verhave G, Plomp J, Bronzwaer P, Wiersma J, Kooy A, Herrman JP, Imholz B, de Groot M, Devlin G, Elliott J, Benatar J, Harding S, Hart H, Young C, Mirek-Bryniarska E, Gniot J, Broncel M, Kozina M, Kus W, Sciborski R, Lesnik J, Kawka-Urbanek T, Krzyzanowski M, Okopien B, Wierzbicka K, Dyczek A, Ochean V, Copaci I, Matei C, Pruna C, Constantinescu M, Minescu B, Stamate C, Boldueva S, Markov V, Alexeeva N, Chizhov P, Supryadkina T, Petrochenkova N, Zrazhevsky K, Barbarash O, Gurevich V, Hranai M, Gergel V, Dzupina A, Uhliar R, Vinanska D, Fazekas F, Bugan W, Saaiman J, Nortje H, Theron H, Bernhardi D, Ramlachan P, Van-Zyl L, Basson M, Venter T, Kim D, Han S, Park G, Hwang K, Rhee M, Cho B, Jeong J, Hong B, Chang K, Garcia Puig J, Fuentes Jiménez F, Nieto Iglesias LJ, Pintó Sala X, Gamez JM, Sánchez Álvarez J, Hernandez García JM, Olsson A, Mooe T, Tengmark BO, Lindholm CJ, Hansen O, Tyden P, Moccetti T, Binder R, Ueng K, Lai W, Shyu K, Hsieh I, Sheu W, Chen J, Altunkeser B, Erkan A, Karpenko O, Kaydashev I, Yagensky A, Kovalenko V, Brunskill J, Barr C, Cecil J, Cahill T, A Gorog D, Bakhai A, Coulson W, Gorog D, Loftus I, Haddad T, Hotchkiss D, Isserman S, Janik M, Weinstein D, Wilson S, Butman S, Hearne S, Khan F, Nadar V, Zelman R, Benton R, Flores E, Kahn B, Soni A, Asbill B, Singal D, Dy J, Foucauld J, Crenshaw B, Rogers W, Aslam A, Lieber I, Shah P, Durr S, Spencer R, Mahal S, Cheng S, Abadier R, Gilmore R, Staniloae C, Miller G, Seals A, Jetty P, Mathis C, Henry S, Murray A, Felten W, Navas J, Gudipati R, Singh N, West S, Sabatino K, Crater T, Amin J, Dosh K, Earl J, Z Jafar M, Gelernt M, Kutner M, Salazar J, Krantzler J, El-Ahdab F, Lader E, Zakhary B, Miller S, Madder R, Khan T, Khan M, Collis W, Evans J, Prodafikas J, Panchal V, Cohen K, Weiss R, Dietrich D, Vogel C, Mascarenhas V, Seaworth J, Teklinski A, Davalos J, Dehning M, Herzog W, Snyder H, Talano J, Donahoe S, Hunter J, Sandoval J, Batchelor W, Brautigam D, Moriarty K, Siachos A, Kereiakes D, Traboulssi M, Arif I, Kosinski E, Quadrel M, DeHart D, Miller M, Poock J, Loh I, van Cleeff M, Georgeson S, Suryanarayana P, Cohn J, Schmedtje J, Lamas G, DeSantis J, Stahl L, Prashad R, Schuchard T, Schramm E, Rao V, Deen C, Soufer J, Gurbel P, Vazquez-Tanus J, Srivastava S, Ballantyne C, Lotun K, Younis L, Gupta D, Yeoman G, Zebrack J, Knutson T, Whitaker J, Appel M, Koren M, Muneer B, Fairlamb J, Aviles R, Kozlowski L, Rees A, Stephens M, Mays M, Downey H, Almassi H, Peichert D, Rocco M, French W, Bhatia P, Hoch J, Peart B, Carmichael P, Acheatel R, Vo A, Kirtane A, Bhagwat R, Gilchrist I, Labroo A, Pollock S, Bacon J, Karunaratne H, Moursi M, Doshi A, Sethi P, Treasure C, Marple R, Goodwin T, Zayas-Torres C, Loussararian A, Korn D, Paster R, Albirini A, Moretto T, Guarnieri T, White L, Kramer J, Shortal B, Maynard K, Raikhel M, Rohatgi A, Melucci M, Masri B, Krichmar P, Morris F, Canto J, Wali A, Comerota A, Ellison W, Degregorio M, Chandrika Parameswaran A, Goldscher D, George W, Mulkay A, Maynard R, Ziada K, Strain J, Hermiller J, Ennis B, Desai V, Al-Joundi B, Azocar J, Claudio J, Perez Vargas E, Loy J, Albert M, Chandler G, Maislos F, Graf R, Rama P, Studeny M, Gimple L, Pytlewski G, Simon H, Islam A, Dillon W, Shah S, Geohas C., Lincoff, Am, Nicholls, Sj, Riesmeyer, J, Barter, Pj, Brewer, Hb, Fox, Kaa, Gibson, Cm, Granger, C, Menon, V, Montalescot, G, Rader, D, Tall, Ar, Mcerlean, E, Wolski, K, Ruotolo, G, Vangerow, B, Weerakkody, G, Goodman, Sg, Conde, D, Mcguire, Dk, Nicolau, Jc, Leiva-Pons, Jl, Pesant, Y, Li, W, Kandath, D, Kouz, S, Tahirkheli, N, Mason, D, Nissen, Se, Del Valle, M, Finnell, Jb, Standley, J, Poi, K, Croaning, J, Tong, Yc, Guerra, Jl, Guasparini, G, Hubert, C, Ardissino, D, Betteridge, J, Borghi, C, Bruckert, E, Chiang, Ce, Cinteza, M, Dalby, Aj, Erlinge, D, Fernandez-Ortiz, A, Ge, J, Gottlieb, S, Goudev, A, Gratsiansky, N, Huber, K, Ilavská, A, Jeong, Mh, Jukema, Jw, Katus, H, Keltai, M, Krum, H, Nielsen, H, Ogawa, H, Ongen, Z, Parkhomenko, A, Raugaliene, R, Renkin, J, Rynkiewicz, A, Steinhubl, S, White, H, Widimsky, P, Zhu, J, Armstrong, P, Ridker, P, Mahaffey, K, Steg, G, Wittes, J, Bhargava, A, Chenier, M, Coleman, C, Cremer, P, Jellis, C, Lahoud, R, Lappe, J, Min, D, Monteleone, P, Newton, D, Stegman, B, Senn, T, Katzan, I, Sharma, J, Uchino, K, Vora, N, Brown, K, Fabec, D, Piper, P, Preston, S, Colombo, T, Pagel-Langenickel, I, Penev, P, Maixing, A, Crowley, K, Sarkar, S, Torosyan, N, Castano, L, Tran, D, Dena, V, Blain, L, Keenan, G, Slade, K, Quinlan, E, Edwards, R, Ren, H, Glenny, J, Maffei, L, Albisu Di Gennaro, J, Caccavo, A, Prado, A, Colombo, H, Luquez, H, Lobo Marquez, L, Hammett, C, Blombery, P, Colquhoun, D, Amerena, J, Howes, L, Cooke, D, Simpson, R, Horowitz, J, Sullivan, D, Proietto, J, Yeo, W, Hirschl, M, Hanusch, U, Drexel, H, Brodmann, M, Wollaert, B, De Wolf, L, Delforge, M, Vanwelden, J, Peeters, A, Siqueira Bodart, J, Montenegro, R, Franken, M, Eliaschewitz, F, Parvanova, Z, Raev, D, Mincheva, V, Kichukov, K, Stoyanov, M, Apostolova, E, Tzekova, M, Dimov, B, Lazov, P, Devedzhiev, T, Dion, D, Poirier, P, Lavoie, Jp, Lonn, E, Shukla, D, Chehayeb, R, Nault, P, Gaudet, D, Tardif, Jc, Beaudry, Y, Bakbak, A, Wong, B, St-Maurice, F, Labonte, R, Polasek, P, Sweet, M, Bhargava, R, Nawaz, S, Pandey, S, Tishler, S, Peterson, S, O’Keefe, D, Genest, J, Syan, R, Leiter, L, Li, H, Ma, W, Ma, C, Xu, D, Li, X, Hala, T, Machova, V, Smejkalova, O, Vodnansky, P, Reichert, P, Velimsky, T, Matuska, J, Machkova, M, Jerabek, O, Kuchar, J, Rasmussen, T, Lindgren, L, Alexandersen, P, Bang, L, Brønnum-Schou, J, Valter, I, Soots, M, Lanno, R, Rosenthal, S, Cottin, Y, Elbaz, M, Lafitte, S, Silvain, J, Coste, P, Rangé, G, Gosse, P, Morel, O, Berrouschot, J, Bourhaial, H, Toursarkissian, N, Appel, Kf, Rieker, W, Stellbrink, C, Münzel, T, Geisler, T, Kadel, C, Giannitsis, E, Trenk, D, vom Dahl, J, Dorsel, T, Singer, O, Schäufele, T, Natour, M, Ozaki, R, Lau, E, Chan, K, Yeung, V, Yu, C, Lakatos, F, Zólyomi, S, Vangel, S, Merkely, B, Szakal, I, Sipos, A, Laszloczky, A, Kis, E, Szocs, A, Szántai, G, Faludi, P, Kancz, S, Oroszlan, T, Hamoud, S, Francis, A, Chorin, E, Leibowitz, D, Kracoff, O, Weisz, G, Schiff, E, Bitzur, R, Hussein, O, Di Lorenzo, L, Visona, A, Mos, L, De Luca, G, Salvioni, A, Rubba, P, Imberti, D, Bucci, M, Saku, K, Sueyoshi, A, Ohshima, K, Kazatani, Y, Shimizu, M, Fujii, K, Higa, N, Kawamitsu, K, Shimomura, H, Hoshizaki, H, Tashiro, H, Baden, M, Ueda, O, Tanabe, J, Momiyama, Y, Hosokawa, S, Takahashi, N, Kimura, K, Fujinaga, H, Masutani, M, Kuramochi, T, Higashikata, T, Ichikawa, S, Yamagishi, M, Sakota, S, Sakuragi, S, Suzuki, M, Taguchi, S, Nakamura, T, Ozaki, Y, Tsujita, K, Yasuda, S, Ando, K, Fujimoto, K, Tanabe, K, Fukunaga, M, Kavaliauskiene, R, Motiejuniene, L, Slapikas, R, Jarasuniene, D, De los Rios Ibarra, M, Alcocer Gamba, M, Nevarez Ruiz, L, Fajardo-Campos, P, Llamas Esperon, G, Violante Ortiz, R, Stobschinski de Alba, C, Guizar Sanchez, C, Guerra Lopez, A, Montano, E, Miracle, S, Fanghanel, G, Lenderink, T, Troquay, R, Van Leendert, R, van Eck, J, Hamer, B, Ronner, E, Karalis, I, Lok, D, Magro, M, Westendorp, I, Stroes, E, De Melker, E, Verhave, G, Plomp, J, Bronzwaer, P, Wiersma, J, Kooy, A, Herrman, Jp, Imholz, B, de Groot, M, Devlin, G, Elliott, J, Benatar, J, Harding, S, Hart, H, C, Young, Mirek-Bryniarska, E, Gniot, J, Broncel, M, Kozina, M, Kus, W, Sciborski, R, Lesnik, J, Kawka-Urbanek, T, Krzyzanowski, M, Okopien, B, Wierzbicka, K, Dyczek, A, Ochean, V, Copaci, I, Matei, C, Pruna, C, Constantinescu, M, Minescu, B, Stamate, C, Boldueva, S, Markov, V, Alexeeva, N, Chizhov, P, Supryadkina, T, Petrochenkova, N, Zrazhevsky, K, Barbarash, O, Gurevich, V, Hranai, M, Gergel, V, Dzupina, A, Uhliar, R, Vinanska, D, Fazekas, F, Bugan, W, Saaiman, J, Nortje, H, Theron, H, Bernhardi, D, Ramlachan, P, Van-Zyl, L, Basson, M, Venter, T, Kim, D, Han, S, Park, G, Hwang, K, Rhee, M, Cho, B, Jeong, J, Hong, B, Chang, K, Garcia Puig, J, Fuentes Jiménez, F, Nieto Iglesias LJ, Pintó Sala, X, Gamez, Jm, Sánchez Álvarez, J, Hernandez García JM, Olsson, A, Mooe, T, Tengmark, Bo, Lindholm, Cj, Hansen, O, Tyden, P, Moccetti, T, Binder, R, Ueng, K, Lai, W, Shyu, K, Hsieh, I, Sheu, W, Chen, J, Altunkeser, B, Erkan, A, Karpenko, O, Kaydashev, I, Yagensky, A, Kovalenko, V, Brunskill, J, Barr, C, Cecil, J, Cahill, T, A Gorog D, Bakhai, A, Coulson, W, Gorog, D, Loftus, I, Haddad, T, Hotchkiss, D, Isserman, S, Janik, M, Weinstein, D, Wilson, S, Butman, S, Hearne, S, Khan, F, Nadar, V, Zelman, R, R, Benton, E, Flore, Kahn, B, Soni, A, Asbill, B, Singal, D, Dy, J, Foucauld, J, Crenshaw, B, Rogers, W, Aslam, A, Lieber, I, Shah, P, Durr, S, Spencer, R, Mahal, S, Cheng, S, Abadier, R, Gilmore, R, Staniloae, C, Miller, G, Seals, A, Jetty, P, Mathis, C, Henry, S, Murray, A, Felten, W, Navas, J, Gudipati, R, Singh, N, West, S, Sabatino, K, Crater, T, Amin, J, Dosh, K, Earl, J, Z Jafar M, Gelernt, M, Kutner, M, J, Salazar, Krantzler, J, El-Ahdab, F, Lader, E, Zakhary, B, Miller, S, Madder, R, Khan, T, Khan, M, Collis, W, Evans, J, Prodafikas, J, Panchal, V, Cohen, K, Weiss, R, Dietrich, D, Vogel, C, Mascarenhas, V, Seaworth, J, Teklinski, A, Davalos, J, Dehning, M, Herzog, W, Snyder, H, Talano, J, Donahoe, S, Hunter, J, Sandoval, J, Batchelor, W, Brautigam, D, Moriarty, K, Siachos, A, Kereiakes, D, Traboulssi, M, Arif, I, Kosinski, E, Quadrel, M, Dehart, D, Miller, M, Poock, J, Loh, I, van Cleeff, M, Georgeson, S, Suryanarayana, P, Cohn, J, Schmedtje, J, Lamas, G, Desantis, J, Stahl, L, Prashad, R, Schuchard, T, Schramm, E, Rao, V, Deen, C, Soufer, J, Gurbel, P, Vazquez-Tanus, J, Srivastava, S, Ballantyne, C, Lotun, K, Younis, L, Gupta, D, Yeoman, G, Zebrack, J, Knutson, T, Whitaker, J, Appel, M, Koren, M, Muneer, B, Fairlamb, J, Aviles, R, Kozlowski, L, Rees, A, Stephens, M, Mays, M, Downey, H, Almassi, H, Peichert, D, Rocco, M, French, W, Bhatia, P, Hoch, J, Peart, B, Carmichael, P, Acheatel, R, Vo, A, Kirtane, A, Bhagwat, R, Gilchrist, I, Labroo, A, Pollock, S, Bacon, J, Karunaratne, H, Moursi, M, Doshi, A, Sethi, P, Treasure, C, Marple, R, Goodwin, T, Zayas-Torres, C, Loussararian, A, Korn, D, Paster, R, Albirini, A, Moretto, T, Guarnieri, T, White, L, Kramer, J, Shortal, B, Maynard, K, Raikhel, M, Rohatgi, A, Melucci, M, Masri, B, Krichmar, P, Morris, F, Canto, J, Wali, A, Comerota, A, Ellison, W, Degregorio, M, Chandrika Parameswaran, A, Goldscher, D, George, W, Mulkay, A, Maynard, R, Ziada, K, Strain, J, Hermiller, J, Ennis, B, Desai, V, Al-Joundi, B, Azocar, J, Claudio, J, Perez Vargas, E, Loy, J, Albert, M, Chandler, G, Maislos, F, Graf, R, Rama, P, Studeny, M, Gimple, L, Pytlewski, G, Simon, H, Islam, A, Dillon, W, Shah, S, Geohas, C., Lincoff, A. Michael, Nicholls, Stephen J., Riesmeyer, Jeffrey S., Barter, Philip J., Brewer, H. Bryan, Fox, Keith A. A., Gibson, C. Michael, Granger, Christopher, Menon, Venu, Montalescot, Gille, Rader, Daniel, Tall, Alan R., Mcerlean, Ellen, Wolski, Kathy, Ruotolo, Giacomo, Vangerow, Burkhard, Weerakkody, Govinda, Goodman, Shaun G., Conde, Diego, Mcguire, Darren K., Nicolau, Jose C., Leiva-Pons, Jose L., Pesant, Yve, Li, Weimin, Kandath, David, Kouz, Simon, Tahirkheli, Naeem, Mason, Denise, Nissen, Steven E., Del Valle M, Young, C, Nieto Iglesias, Lj, Hernandez García, Jm, A Gorog, D, Benton, R, Flores, E, Z Jafar, M, and Salazar, J
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Male ,0301 basic medicine ,Cardiovascular Outcome ,Cholesterol Ester Transfer Protein ,Myocardial Ischemia ,030204 cardiovascular system & hematology ,Coronary artery disease ,cholesteryl ester transfer protein inhibitor ,Benzodiazepines ,chemistry.chemical_compound ,0302 clinical medicine ,Cardiovascular Disease ,Anticholesteremic Agent ,Intracranial Arteriosclerosi ,Treatment Failure ,Evacetrapib ,Peripheral Vascular Diseases ,Benzodiazepine ,biology ,Medicine (all) ,Anticholesteremic Agents ,Diabetes Mellitu ,General Medicine ,Middle Aged ,Intracranial Arteriosclerosis ,High-Risk Vascular Disease ,Editorial ,Cardiovascular Diseases ,Cardiology ,Female ,lipids (amino acids, peptides, and proteins) ,Human ,Risk ,medicine.medical_specialty ,Acute coronary syndrome ,03 medical and health sciences ,Double-Blind Method ,Internal medicine ,Diabetes mellitus ,Cholesterylester transfer protein ,Diabetes Mellitus ,Journal Article ,medicine ,Humans ,Aged ,Cholesterol ,Vascular disease ,business.industry ,Cholesterol, HDL ,Biomarker ,Cholesterol, LDL ,medicine.disease ,Cholesterol Ester Transfer Proteins ,Surgery ,030104 developmental biology ,Peripheral Vascular Disease ,chemistry ,biology.protein ,business ,Biomarkers ,Lipoprotein - Abstract
BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .).
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- 2017
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3. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
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Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ, Novo S, Krum H, Varigos J, Siostrzonek P, Sinnaeve P, Gotcheva N, Yong H, Urina-Triana M, Milicic D, Vettus R, Manolis AJ, Wyss F, Sigurdsson A, Fucili A, Veze I, Petrauskiene B, Salvador L, Klemsdal TO, Medina F, Budaj A, Otasevic P, Lainscak M, Seung KB, Commerford P, Donath M, Hwang JJ, Kultursay H, Bilazarian S, East C, Forgosh L, Harris B, Ligueros M, Bohula E, Charmarthi B, Cheng S, Chou S, Danik J, McMahon G, Maron B, Ning M, Olenchock B, Pande R, Perlstein T, Pradhan A, Rost N, Singhal A, Taqueti V, Wei N, Burris H, Cioffi A, Dalseg AM, Ghosh N, Gralow J, Mayer T, Rugo H, Fowler V, Limaye AP, Cosgrove S, Levine D, Lopes R, Scott J, Hilkert R, Tamesby G, Mickel C, 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0301 basic medicine ,030204 cardiovascular system & hematology ,law.invention ,0302 clinical medicine ,c-reactive protein ,Randomized controlled trial ,law ,Cardiovascular Disease ,middle aged ,double-blind method ,antibodies ,Myocardial infarction ,humans ,Stroke ,interleukin-1beta ,biology ,Antibodies, Monoclonal ,drug ,General Medicine ,Lipid ,Aged ,anti-inflammatory agents ,monoclonal ,humanized ,atherosclerosis ,cardiovascular diseases ,dose-response relationship ,female ,incidence ,infections ,lipids ,male ,myocardial infarction ,neutropenia ,secondary prevention ,stroke ,Anti-Inflammatory Agent ,aged ,Editorial ,Atherosclerosi ,Monoclonal ,Human ,medicine.drug ,medicine.medical_specialty ,Neutropenia ,Antibodies, Monoclonal, Humanized ,Infections ,Placebo ,antibodies, monoclonal ,dose-response relationship, drug ,infection ,medicine (all) ,03 medical and health sciences ,Internal medicine ,medicine ,Dose-Response Relationship, Drug ,business.industry ,Antiinflammatory Therapy, Canakinumab, for Atherosclerotic Disease ,C-reactive protein ,medicine.disease ,Surgery ,Canakinumab ,030104 developmental biology ,biology.protein ,business - Abstract
Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.)
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- 2017
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4. Liraglutide and Renal Outcomes in Type 2 Diabetes
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Mann JFE, Ørsted DD, Brown-Frandsen K, Marso SP, Poulter NR, Rasmussen S, Tornøe K, Zinman B, Buse JB, LEADER Steering Committee and Investigators. 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E, Martinez G, Martinez-Miss S, Marx P, Massara L, Mastoor M, Matfin G, Maturu A, Maurides P, May M, Mayfield R, Maynard B, Mazza A, McCann K, McCoy J, McCoy T, McCullen MK, McDaniel C, McDaniel AM, McDermott M, McDonald A, McMasters B, McMurray C, Medlin T, Meinel M, Mendez I, Menefee J, Meredith M, Merriweather M, Mersey J, Messino C, Meyer S, Meyers L, Michael D, Midyett C, Miklius A, Milford E, Miller B, Miller H, Milligan M, Minor A, Miranda-Palma B, Mirarchi N, Mittadodla S, Mittle J, Moffat A, Mohaupt S, Mohiuddin K, Mokshagundam S, Monaco S, Monsaert R, Montano-Pereira C, Montgomery A, Moody K, Moon M, Moore D, Moore L, Morawski E, Moreau C, Morin D, Moscoa C, Motzkin C, Mueller R, Munoz C, Munoz M, Myneni A, Naderi B, Nagireddy P, Naidu J, Naidu R, Naik S, Naimark R, Nardicchi M, Ndukwu I, Neller C, Netten-Foster L, Neumiller J, New T, Newman S, Newton T, Nguyen B, Nicol B, Nicol P, Ninivaggi L, Niswender K, Norman L, Noworatzky G, Nyenwe E, O'Brien H, O'Connell T, Oden W, Odugbesan A, Oliver M, Oliver T, Olmeda C, O'Neil C, Oremus R, Ortega T, Ortiz-Santos S, Osborn T, Padmanabhan S, Papacostea O, Park I, Parker A, Parker K, Parker R, Patel C, Patel M, Patel R, Patino M, Patterson S, Paulson K, Paz A, Pemba R, Pepe C, Perez J, Perez T, Perry D, Phillips B, Phillips J, Pickett A, Pinson M, Pitzer R, Poduri M, Poehls J, Poteat T, Powell L, Prasad S, Prevost J, Price E, Priest D, Prieto L, Purewal T, Purighalla R, Purighalla U, Quadrel M, Qureshi A, Radhamma R, Rafla E, Rajab H, Ramalingam R, Ramirez A, Ramirez J, Ramirez K, Ramirez M, Randall M, Rangaraj U, Rao V, Rasmussen P, Rasouli N, Ray A, Reed J, Rems L, Renaud K, Reno M, Resnick M, Reusch J, Reynolds L, Rhoton K, Rhudy J, Ricci C, Rice L, Richardson A, Richardson L, Rickard H, Rickels M, Riff D, Rightenour N, Risser J, Rizvi A, Robertson J, Robinson A, Robinson R, Rockwell M, Rodriguez JP, Rodriguez M, Rojas M, Rojas W, Rooker-Morris L, Root C, Rose M, Rosenberg R, Rosenstock J, Roth M, Ruby R, 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Sutton T, Tabbah I, Talsania M, Tang R, Tapia J, Taylor K, Taylor-Hancher R, Teator R, Tekateka M, Temple B, Temple K, Teodori M, Tharp P, Thethi T, Theuma P, Thomas S, Thottan A, Thrasher J, Thrasher L, Tiemeyer M, Tinney I, Tobin T, Toma S, Tovar M, Townsend J, Trantow C, Traylor H, Trevino M, Troy M, Trumper D, Tryggestad J, Tucker C, Turner J, Turney R, Tuten C, Tyzack J, Ullo L, Underkofler C, Unger J, Urdanetta R, Valdivia V, Valenti S, Vanderheiden A, Vanderlinde-Wood M, Varma C, Vasquez E, Vazquez M, Vickery D, Villafuerte B, Villegas C, Vivar J, Vivekananthan K, Vo G, Vukojicic K, Wachter A, Wahl D, Waitmann J, Walker D, Walsh J, Walsh K, Walton A, Wang A, Wardell K, Watkins S, Watkinson J, Watts M, Watwe V, Weaver N, Weber R, Wedick C, Weeks D, Weeks L, Weindorff K, Weinstein R, Weiss S, Wenger K, Wentworth M, Werner A, West M, Whelan S, White B, White J, Whitmire M, Whittington R, Wical J, Wigley C, Wilkins F, Will K, Williams A, Wilson LE, Wince M, Wine S, Winkle P, Winner C, Wise J, Witte M, Wittenmyer J, Wood C, Wood R, Woodruff C, Worthington B, Wynn D, Wysham C, Xavier P, Yela S, Yenoby L, Young L, Younus N, Yourell V, Zaid M, Zubair I., Mann, Jfe, Ørsted, Dd, Brown-Frandsen, K, Marso, Sp, Poulter, Nr, Rasmussen, S, Tornøe, K, Zinman, B, Buse, Jb, Bergenstal R, LEADER Steering Committee and Investigators., Daniels, G, Moses, Ac, Nauck, M, Nissen, S, Pocock, S, Steinberg, W, Stockner, M, Kristensen, P, Ravn, L, Zychma, M, Flyvbjerg, A, Ford, I, Kloos, Rt, Schactman, Mj, Sleight, P, Swedberg, K, Tenner, Sm, Akalın, S, Arechavaleta, R, Bain, S, Babkowski, Mc, Benroubi, M, Berard, L, Comlekci, A, Czupryniak, L, Eliasson, B, Eriksson, M, Fonseca, V, Franek, E, Gross, J, Hafidh, K, Haluzik, M, Hayes, F, Huang, Yy, Jacob, S, Kaddaha, G, Khalil, A, Kilhovd, B, Laakso, M, Leiter, L, Lalic, N, Ji, L, Luedemann, J, Mannucci, E, Marre, M, Masmiquel, L, Mota, M, Omar, M, O’Shea, D, Pan, C, Petrie, J, Pieber, T, Pratley, R, Raz, I, Rea, R, Rutten, G, Satman, I, 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Resnick, M, Reusch, J, Reynolds, L, Rhoton, K, Rhudy, J, Ricci, C, Rice, L, Richardson, A, Richardson, L, Rickard, H, Rickels, M, Riff, D, Rightenour, N, Risser, J, Rizvi, A, Robertson, J, Robinson, A, Robinson, R, Rockwell, M, Rodriguez, Jp, Rodriguez, M, Rojas, M, Rojas, W, Rooker-Morris, L, Root, C, Rose, M, Rosenberg, R, Rosenstock, J, Roth, M, Ruby, R, Sachson, R, Sack, P, Sadler, Rk, Sahai, S, J, Salazar, Salgam, M, Samal, A, Samson, A, Sanagorski, R, Sanchez, A, Sandberg, J, Sanderson, M, Sandoval, J, Santiago, E, Sapp, T, Saunders, J, Schill, J, Schott, C, Schreiman, R, Schu, D, Schuh, K, Schutta, M, Schwartz, J, Schweppe, L, Scofield, H, Scribner, A, Seal, J, Sealock, J, Seaton, B, Sedlak-Hanslik, T, Seekins, K, Segal, M, Seggelke, S, Semenza, S, Sentman, P, Serra, M, Seshadri, P, Sevilla, E, Shah, S, Shaheen, K, Shanik, M, Shaw, J, Sheets, M, Shellabarger, C, Sher, J, Shippey, J, Shivaswamy, V, Shomali, M, Shore, D, Shroff, P, Siddiqui, T, Siegwald, A, Silver, R, Simmons, D, Simons, R, Sinan, A, Singh, M, Sirinvaravong, S, Skero, J, Slover-Zipf, J, Small, S, Smith, B, Smith, K, Smith, M, Sohl, J, Solarz, Sh, Soler, D, Sood, A, Sora, N, Souchet, A, Soule, J, Sparks, J, Spector, L, Speicher, R, Spillers, L, Spivey, T, Springer, N, Sprouse, H, St John, J, Stacey, A, Stacey, H, Stafford, M, Stagner, E, Staples, K, Steadman, E, Steed, R, Steeves, G, Steinberg, H, Stell, C, Stirman, E, Straub, K, Strock, E, Sue, M, Suris, O, Sutton, T, Tabbah, I, Talsania, M, Tang, R, Tapia, J, Taylor, K, Taylor-Hancher, R, Teator, R, Tekateka, M, Temple, B, Temple, K, Teodori, M, Tharp, P, Thethi, T, Theuma, P, Thomas, S, Thottan, A, Thrasher, J, Thrasher, L, Tiemeyer, M, Tinney, I, Tobin, T, Toma, S, Tovar, M, Townsend, J, Trantow, C, Traylor, H, Trevino, M, Troy, M, Trumper, D, Tryggestad, J, Tucker, C, Turner, J, Turney, R, Tuten, C, Tyzack, J, Ullo, L, Underkofler, C, Unger, J, Urdanetta, R, Valdivia, V, Valenti, S, Vanderheiden, A, Vanderlinde-Wood, M, Varma, C, Vasquez, E, Vazquez, M, Vickery, D, Villafuerte, B, Villegas, C, Vivar, J, Vivekananthan, K, Vo, G, Vukojicic, K, Wachter, A, Wahl, D, Waitmann, J, Walker, D, Walsh, J, Walsh, K, Walton, A, Wang, A, Wardell, K, Watkins, S, Watkinson, J, Watts, M, Watwe, V, Weaver, N, Weber, R, Wedick, C, Weeks, D, Weeks, L, Weindorff, K, Weinstein, R, Weiss, S, Wenger, K, Wentworth, M, Werner, A, West, M, Whelan, S, White, B, White, J, Whitmire, M, Whittington, R, Wical, J, Wigley, C, Wilkins, F, Will, K, Williams, A, Wilson, Le, Wince, M, Wine, S, Winkle, P, Winner, C, Wise, J, Witte, M, Wittenmyer, J, Wood, C, Wood, R, Woodruff, C, Worthington, B, Wynn, D, Wysham, C, Xavier, P, Yela, S, Yenoby, L, Young, L, Younus, N, Yourell, V, Zaid, M, Zubair, I., Mann J.F.E., Orsted D.D., Brown-Frandsen K., Marso S.P., Poulter N.R., Rasmussen S., Tornoe K., Zinman B., Buse J.B., and Buscemi S.
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Male ,Settore MED/09 - Medicina Interna ,Acute Kidney Injury ,Aged ,Albuminuria ,Creatinine ,Diabetes Mellitus, Type 2 ,Diabetic Nephropathies ,Double-Blind Method ,Female ,Follow-Up Studies ,Glomerular Filtration Rate ,Glucagon-Like Peptide 1 ,Humans ,Hypoglycemic Agents ,Intention to Treat Analysis ,Kidney Failure, Chronic ,Liraglutide ,Middle Aged ,Type 2 diabetes ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,GLOMERULAR-FILTRATION-RATE ,KIDNEY-FUNCTION ,DISEASE ,law.invention ,Kidney Failure ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Medicine ,Settore MED/49 - Scienze Tecniche Dietetiche Applicate ,Chronic ,RISK ,Kidney ,Acute kidney injury ,11 Medical And Health Sciences ,General Medicine ,medicine.anatomical_structure ,TRIAL ,liraglutide, randomized controlled trial, type 2 diabetes, renal outcomes ,Life Sciences & Biomedicine ,Type 2 ,medicine.drug ,medicine.medical_specialty ,Renal function ,030209 endocrinology & metabolism ,CARDIOVASCULAR OUTCOMES ,Follow-Up Studie ,03 medical and health sciences ,Medicine, General & Internal ,General & Internal Medicine ,Diabetes mellitus ,Internal medicine ,Diabetes Mellitus ,Intensive care medicine ,Science & Technology ,business.industry ,MORTALITY ,medicine.disease ,INTENSIVE GLUCOSE CONTROL ,INDIVIDUALS ,chemistry ,Diabetic Nephropathie ,LEADER Steering Committee and Investigators ,business - Abstract
BACKGROUND: In a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown. METHODS: We report the prespecified secondary renal outcomes of that randomized, controlled trial in which patients were assigned to receive liraglutide or placebo. The secondary renal outcome was a composite of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease, or death due to renal disease. The risk of renal outcomes was determined with the use of time-to-event analyses with an intention-to-treat approach. Changes in the estimated glomerular filtration rate and albuminuria were also analyzed. RESULTS: A total of 9340 patients underwent randomization, and the median follow-up of the patients was 3.84 years. The renal outcome occurred in fewer participants in the liraglutide group than in the placebo group (268 of 4668 patients vs. 337 of 4672; hazard ratio, 0.78; 95% confidence interval [CI], 0.67 to 0.92; P=0.003). This result was driven primarily by the new onset of persistent macroalbuminuria, which occurred in fewer participants in the liraglutide group than in the placebo group (161 vs. 215 patients; hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P=0.004). The rates of renal adverse events were similar in the liraglutide group and the placebo group (15.1 events and 16.5 events per 1000 patient-years), including the rate of acute kidney injury (7.1 and 6.2 events per 1000 patient-years, respectively). CONCLUSIONS: This prespecified secondary analysis shows that, when added to usual care, liraglutide resulted in lower rates of the development and progression of diabetic kidney disease than placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .).
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- 2017
5. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management
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Pi-Sunyer, Xavier, Astrup, Arne, Fujioka, Ken, Greenway, Frank, Halpern, Alfredo, Krempf, Michel, Lau, David C. W., le Roux, Carel W., Ortiz, Violante, Jensen, Christine Bjorn, Wilding, John P. H., Hamann, A, Barakat, A, Blüher, M, Linn, T, DALLE MOLLE, Alberto, Segner, A, Stübler, P, Tosch-Sisting, R, Pacini, F, Santini, F, Marchesini, G, Rotella, Cm, Invitti, C, Vettor, R, Buscemi, S, Raya, Pm, Freijoo, Fc, de Barbará RG, Carraro, R, Bobillo, Er, de la Cuesta, C, Farsang, C, Csaszar, A, Zahorska-Markiewicz, B, Pupek-Musialik, D, Franek, E, Ostrowska, L, Olszanecka-Glinianowicz, M, Lalic, N, Micic, D, Ludvik, B, Paulweber, B, Prager, R, Scheen, A, Van Gaal, L, Astrup, Av, Hermansen, K, Madsbad, S, Rissanen, A, Nieminen, S, Savolainen, M, Krempf, M, Romon, M, Laville, M, Marre, M, Mira, R, Finucane, F, Veenendaal, A, van Berkum, F, Johannsson-Vidarsdóttir, S, Van de Walle, V, Meesters, E, Hjelmesæth, J, Klemsdal, To, Kulseng, B, Bach-Kliegel, B, Laederach, K, Villiger, L, Golay, A, Bilz, S, Sathyapalan, T, Bain, S, Kumar, S, Le Roux CW, Lean, Me, Mcgowan, B, Rehman, T, Wilding, J, Wittert, G, Caterson, I, Proietto, J, Prins, J, Geloneze Neto, B, Gross, Jl, Chacra, Ar, Halpern, A, Suplicy Hde, A, Chow, Fc, Thacker, Hp, Chadha, M, Chandalia, H, Unnikrishnan, A, Kalra, S, Deshpande, N, Shunmugavelu, M, Deshmukh, Vc, Maislos, M, Lieberman, Gs, Shimon, I, Stern, N, Nabriski, D, Karnieli, E, Shehadeh, N, Gonzalez-Galvez, G, Arechavaleta-Granell Mdel, R, Violante Ortiz RM, Franco, Gm, Gurieva, I, Suplotova, La, Troshina, E, Ruyatkina, La, Voychik, Ea, Martsevich, S, Startseva, Ma, Seeber, Me, Badat, A, Ellis, G, Altuntas, Y, Guler, S, Ulgen, E, Delibasi, T, Chetty, T, Hart, R, Janzen, J, Labonte, I, Lau, D, Liutkus, J, O'Keefe, D, Padwal, R, Ransom, Tp, Tytus, R, Weisnagel, Sj, Adler, J, Aqua, K, Aronoff, Sl, Bedel, Gw, Blevins, Tc, Blumenau, J, Brockmyre, Ap, Call, Rs, Canadas, R, Chaykin, Lb, Cohen, K, Conrow, Jk, Davis, Mg, Downey, Hj, Drosman, Sr, Duckor, S, Farmer, H, Farrell, J, Fehnel, S, Finneran, Mp, Forbes, R, Forker, A, Fredrick, M, Fujioka, K, Geller, Sa, Gill, S, Glaser, L, Greco, Sn, Greenway, Fl, Harper, W, Herman, L, Hoekstra, J, Ingebretsen, R, Ison, R, Jain, Rk, Kaplan, R, Kaster, Sr, Haase, Ga, Kerzner, B, Kirstein, Jl, Koltun, W, Krieger, Dr, Lewis, Ce, Madder, R, Marple, Rn, Mcdermott, Ej, Mello, Cj, Miller, Ab, Mullen, J, Nardandrea, J, O'Neil, P, Pi-Sunyer, F, Pucillo, Rm, Rhee, C, Redrick, S, Pardini, A, Rothman, J, Rubino, Dm, Sellers, G, Smith, T, Byars, Wd, Soufer, J, Sussman, Am, Patrick, K, Schramm, El, Van Cleeff, M, Berg, Sr, Wyatt, Hr, Simon, Ja., Columbia University [New York], Obesity Research Center, The University of Tennessee [Knoxville], Department of Nutrition, Exercise and Sports [Copenhagen], Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Scripps Research Institute, Louisiana State University (LSU), Universidade de São Paulo (USP), Centre hospitalier universitaire de Nantes (CHU Nantes), University of Calgary, University College Dublin (UCD), Instituto Mexicano del Seguro Social [Mexico City, Mexico] (IMSS), Novo Nordisk, Department of Obesity and Endocrinology, University of Liverpool, Pi-Sunyer, Xavier, Astrup, Arne, Fujioka, Ken, Greenway, Frank, Halpern, Alfredo, Krempf, Michel, Lau, David C.W., Le Roux, Carel W., Ortiz, Rafael Violante, Jensen, Christine Bjørn, Wilding, John P.H., the SCALE Obesity and Prediabetes NN8022-1839 Study Group [.., Marchesini, Giulio, ], Pi-Sunyer, X., Astrup, A., Fujioka, K., Greenway, F., Halpern, A., Krempf, M., Lau, D., le Roux, C., Violante Ortiz, R., Jensen, C., Wilding, J. COLLABORATORS: amann A, Barakat A, Blüher M, Linn T, Mölle A, Segner A, Stübler P, Tosch-Sisting R, Pacini F, Santini F, Marchesini G, Rotella CM, Invitti C, Vettor R, Buscemi S, and Raya PM, Freijoo FC, de Barbará RG, Carraro R, Bobillo ER, de la Cuesta C, Farsang C, Csaszar A, Zahorska-Markiewicz B, Pupek-Musialik D, Franek E, Ostrowska L, Olszanecka-Glinianowicz M, Lalic N, Micic D, Ludvik B, Paulweber B, Prager R, Scheen A, Van Gaal L, Astrup AV, Hermansen K, Madsbad S, Rissanen A, Nieminen S, Savolainen M, Krempf M, Romon M, Laville M, Marre M, Mira R, Finucane F, Veenendaal A, van Berkum F, Johannsson-Vidarsdóttir S, Van de Walle V, Meesters E, Hjelmesæth J, Klemsdal TO, Kulseng B, Bach-Kliegel B, Laederach K, Villiger L, Golay A, Bilz S, Sathyapalan T, Bain S, Kumar S, Le Roux CW, Lean ME, McGowan B, Rehman T, Wilding J, Wittert G, Caterson I, Proietto J, Prins J, Geloneze Neto B, Gross JL, Chacra AR, Halpern A, Suplicy Hde A, Chow FC, Thacker HP, Chadha M, Chandalia H, Unnikrishnan A, Kalra S, Deshpande N, Shunmugavelu M, Deshmukh VC, Maislos M, Lieberman GS, Shimon I, Stern N, Nabriski D, Karnieli E, Shehadeh N, Gonzalez-Galvez G, Arechavaleta-Granell Mdel R, Violante Ortiz RM, Franco GM, Gurieva I, Suplotova LA, Troshina E, Ruyatkina LA, Voychik EA, Martsevich S, Startseva MA, Seeber ME, Badat A, Ellis G, Altuntas Y, Guler S, Ulgen E, Delibasi T, Chetty T, Hart R, Janzen J, Labonte I, Lau D, Liutkus J, O'Keefe D, Padwal R, Ransom TP, Tytus R, Weisnagel SJ, Adler J, Aqua K, Aronoff SL, Bedel GW, Blevins TC, Blumenau J, Brockmyre AP, Call RS, Canadas R, Chaykin LB, Cohen K, Conrow JK, Davis MG, Downey HJ, Drosman SR, Duckor S, Farmer H, Farrell J, Fehnel S, Finneran MP, Forbes R, Forker A, Fredrick M, Fujioka K, Geller SA, Gill S, Glaser L, Greco SN, Greenway FL, Harper W, Herman L, Hoekstra J, Ingebretsen R, Ison R, Jain RK, Kaplan R, Kaster SR, Haase GA, Kerzner B, Kirstein JL, Koltun W, Krieger DR, Lewis CE, Madder R, Marple RN, McDermott EJ, Mello CJ, Miller AB, Mullen J, Nardandrea J, O'Neil P, Pi-Sunyer F, Pucillo RM, Rhee C, Redrick S, Pardini A, Rothman J, Rubino DM, Sellers G, Smith T, Byars WD, Soufer J, Sussman AM, Patrick K, Schramm EL, Van Cleeff M, Berg SR, Wyatt HR, Simon JA.
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Blood Glucose ,Counseling ,Male ,Type 2 diabetes ,law.invention ,Body Mass Index ,Randomized controlled trial ,Weight loss ,law ,Glucagon-Like Peptide 1 ,Weight management ,Subcutaneous ,Medicine (all) ,Reducing ,Nausea ,General Medicine ,Middle Aged ,Combined Modality Therapy ,3. Good health ,Female ,type 2 diabetes ,medicine.symptom ,Human ,medicine.drug ,Adult ,Diarrhea ,medicine.medical_specialty ,Diet, Reducing ,Injections, Subcutaneous ,Injections, Subcutaneou ,Placebo ,Injections ,Double-Blind Method ,Internal medicine ,Weight Loss ,medicine ,Humans ,Hypoglycemic Agents ,Obesity ,Exercise ,Hypoglycemic Agent ,Liraglutide ,business.industry ,medicine.disease ,Weight Lo ,Diet ,Endocrinology ,business ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,Body mass index ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Dyslipidemia - Abstract
BACKGROUND: Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagon-like peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. METHODS: We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. RESULTS: At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P
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- 2015
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6. A Single Center Experience of the Impella RP in Acute Right Ventricular Failure
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Proudfoot, A., primary, Mulder, A., additional, Maragiri, S., additional, Pardington, E., additional, Osip, E., additional, Ten Brock, T., additional, VanOosterhout, S., additional, Madder, R., additional, and Lee, S., additional
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- 2018
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7. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events
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Robinson, Jg, Farnier, M, Krempf, M, Bergeron, J, Luc, G, Averna, M, Stroes, Es, Langslet, G, Raal, Fj, El Shahawy, M, Koren, Mj, Lepor, Ne, Lorenzato, C, Pordy, R, Chaudhari, U, Kastelein, Jj, Caccavo, A, Codutti, O, Gelersztein, E, Vico, M, Zaidman, C, Majul, C, Balthazar, Y, Capiau, L, Vrolix, M, Vermeersch, P, Gotchev, D, Todorov, G, Tumbev, H, Tzekova, M, Gronkova, N, Dimov, B, Nikolaeva, A, Devedzhiev, T, Mincheva, V, D'Ignazio, G, Dzongowski, P, Elliott, T, Hart, R, Hoag, G, Martinho, V, O'Mahony, M, Tellier, G, Pandey, S, Heaton, K, Constance, C, Phaneuf, Dc, Shu, D, Narvaez, Nc, Cañon, Co, Cardenas, Sp, Loayza, Ms, de Salazar, Dm, Lopez, Rb, Gomez, Ji, Mendoza, Ja, Cure, Cc, Ceska, R, Zidkova, E, Jansky, P, Egstrup, K, Klausen, Ib, Lomholdt, J, Gislason, G, Torp Pedersen, C, Poulsen, S, Kuusela, M, Kekki, S, Nieminen, S, Tuomilehto, J, Boye, A, Bruckert, E, Cadinot, D, Lejay, D, Revol, T, Schaupp, T, Bonnet, J, Paillard, F, Moulin, P, Junggeburth, J, Isermann, B, Zühlke, M, Züchner, D, Theis, E, Stößel, J, König, Hj, Rinke, A, Piechatzek, R, Contzen, C, Lappo, M, Himpel Boenninghoff, Aa, Meissner, G, Maus, O, Degtyareva, E, Schulze, Ed, Horacek, T, Marten, I, Becher, P, Matoltsy, A, Nyirati, G, Paragh, G, Zilahi, Z, Nagy, K, Kanakaridisz, N, Beke, E, Biro, J, Schnabel, R, Elias, M, Gavish, D, Francis, A, Nseir, W, Zimlichman, R, Pozzi, C, Lembo, G, Bucci, M, Mezzetti, A, De Pellegrin, Am, Salvioni, A, De Cesare, N, Briones, Ir, Campos, Pf, Rosas, El, Espinosa, Ev, Salazar, Ma, Ruiz, Ab, Furusho, Lc, Olvera, I, Stroes, E, van den Berg, R, Basart, D, Köse, V, Kentgens, S, Peeters, M, Hoogendijk, J, Voors Pette, C, Agous, I, van Kempen, W, Lingan, Gr, Kooy, A, Troquay, R, Herrman, J, Hoivik, H, Norheim, P, Risberg, K, Høivik, Ho, Elle, S, Derezinski, T, Miekus, P, Ogorek, M, Szymkowiak, K, Cesar, M, Gawron, A, Dabrowska, M, Blach, E, Konieczny, M, Sidor, M, Matias, F, da Silva, Pm, Carvalho, D, Mendonca, I, Andor, M, Andrei, L, Podoleanu, C, Pop, C, Chizhov, P, Chumakova, G, Goloschekin, B, Libov, I, Paltsman, Z, Strutinskiy, A, Koziolova, N, Breedt, J, Ebrahim, I, Ellis, G, Fulat, M, van Rensburg, Dj, Raal, F, van Dyk, C, Vally, T, van der Walt, E, Kotzé, H, Landman, C, Tayob, M, Caixas, A, García, Lr, Fernandez Cruz, A, Gil Extremera, B, Grijalvo, Om, Plana, N, Fuentes, F, Valdivielso, P, Fraile, B, Borgencrantz, B, Larnefeldt, H, Tengmark, Bo, Eriksson, M, Olsson Önerud, Å, Amalyan, W, Dyadyk, O, Koval, O, Kushnir, M, Svintsitskiy, A, Kovalyov, O, Bondarchuk, O, Tashchuk, V, Barna, O, Prokhorov, O, Karpenko, O, Stanciu, D, Pawa, R, Balaji, H, Doig, F, Harvey, P, Ranganath, L, Massalski, W, Hassanin, H, Timmis, H, Pavel Knox, I, Abdulhakim, E, Oyesile, B, Horvathova, V, Donnachie, H, Kondagunta, V, Shaw, H, Thomas, H, Kadr, H, Gunstone, A, Lip, G, Ellery, A, Kerrane, J, Sarker, A, Wong, Yk, Soran, H, Maw, K, Andersen, J, Blair Britt, L, Huffman, C, Kivitz, A, Marple, R, Patron, A, Schear, M, Allegar, N, Awasty, V, Casanova, R, Chaykin, L, Cohen, L, Collins, H, Collins, G, Elkin, G, Reyes, H, Feld, L, Fuller, G, Glover, R, Greenwald, J, Herrod, J, Kaye, W, Kimmel, M, Kolettis, E, Lakin, G, Lorch, D, Palatnik, M, Patel, R, Reichman, A, Rohlf, J, Shockey, G, Shore, K, Radin, D, Alvarado, O, Bellingar, B, Egelhof, R, Mcknight, T, Plevin, S, Pritchard, J, Reddy, R, Velazquez, F, Bolster, E, Broker, R, Butuk, D, Cheung, D, Cohen, K, Golden, G, Murray, A, Naccarato, T, Uusinarkaus, K, Pudi, K, Graff, A, Blumberg, V, Dunn, F, Toth, P, Anspach, R, Chuang, R, Meli, J, Nevins, B, Wayne, J, Schmidt, L, Levinsky, D, Rubino, J, Shealy, N, Torres, D, West, J, Jain, R, Vardi, G, Singh, N, Thew, S, Lo, E, Heitner, J, Gerber, J, Malik, A, Weinstein, D, Prashad, R, Koren, M, Ghitis, A, David, W, Reis, G, Kinzfogl, G, Haught, H, Kantaros, L, O'Dea, D, Weiss, D, Kassas, S, Hunter, J, Mollod, M, Khan, N, Henderson, D, Gatien, L, Schramm, R, Madder, R, Voyce, S, Nadar, V, Stich, M, Kumar, M, Black, R, Treasure, C, Lebeis, M, Mccullough, P, Lepor, N, Moriarty, P, Waxler, A, Talreja, D, Gen, M, Dohad, S, East, C, Conrad, G, Asbill, B, Roberts, J, Robinson, J, Zarich, S, Davis, B, Krolick, M, Sherman, H, Thompson, P., RUBBA, PAOLO OSVALDO FEDERICO, Robinson, Jg, Farnier, M, Krempf, M, Bergeron, J, Luc, G, Averna, M, Stroes, E, Langslet, G, Raal, Fj, El Shahawy, M, Koren, Mj, Lepor, Ne, Lorenzato, C, Pordy, R, Chaudhari, U, Kastelein, Jj, Caccavo, A, Codutti, O, Gelersztein, E, Vico, M, Zaidman, C, Majul, C, Balthazar, Y, Capiau, L, Vrolix, M, Vermeersch, P, Gotchev, D, Todorov, G, Tumbev, H, Tzekova, M, Gronkova, N, Dimov, B, Nikolaeva, A, Devedzhiev, T, Mincheva, V, D'Ignazio, G, Dzongowski, P, Elliott, T, Hart, R, Hoag, G, Martinho, V, O'Mahony, M, Tellier, G, Pandey, S, Heaton, K, Constance, C, Phaneuf, Dc, Shu, D, Narvaez, Nc, Cañon, Co, Cardenas, Sp, Loayza, M, de Salazar, Dm, Lopez, Rb, Gomez, Ji, Mendoza, Ja, Cure, Cc, Ceska, R, Zidkova, E, Jansky, P, Egstrup, K, Klausen, Ib, Lomholdt, J, Gislason, G, Torp Pedersen, C, Poulsen, S, Kuusela, M, Kekki, S, Nieminen, S, Tuomilehto, J, Boye, A, Bruckert, E, Cadinot, D, Lejay, D, Revol, T, Schaupp, T, Bonnet, J, Paillard, F, Moulin, P, Junggeburth, J, Isermann, B, Zühlke, M, Züchner, D, Theis, E, Stößel, J, König, Hj, Rinke, A, Piechatzek, R, Contzen, C, Lappo, M, Himpel Boenninghoff, Aa, Meissner, G, Maus, O, Degtyareva, E, Schulze, Ed, Horacek, T, Marten, I, Becher, P, Matoltsy, A, Nyirati, G, Paragh, G, Zilahi, Z, Nagy, K, Kanakaridisz, N, Beke, E, Biro, J, Schnabel, R, Elias, M, Gavish, D, Francis, A, Nseir, W, Zimlichman, R, Pozzi, C, Lembo, G, Bucci, M, Mezzetti, A, Rubba, PAOLO OSVALDO FEDERICO, De Pellegrin, Am, Salvioni, A, De Cesare, N, Briones, Ir, Campos, Pf, Rosas, El, Espinosa, Ev, Salazar, Ma, Ruiz, Ab, Furusho, Lc, Olvera, I, van den Berg, R, Basart, D, Köse, V, Kentgens, S, Peeters, M, Hoogendijk, J, Voors Pette, C, Agous, I, van Kempen, W, Lingan, Gr, Kooy, A, Troquay, R, Herrman, J, Hoivik, H, Norheim, P, Risberg, K, Høivik, Ho, Elle, S, Derezinski, T, Miekus, P, Ogorek, M, Szymkowiak, K, Cesar, M, Gawron, A, Dabrowska, M, Blach, E, Konieczny, M, Sidor, M, Matias, F, da Silva, Pm, Carvalho, D, Mendonca, I, Andor, M, Andrei, L, Podoleanu, C, Pop, C, Chizhov, P, Chumakova, G, Goloschekin, B, Libov, I, Paltsman, Z, Strutinskiy, A, Koziolova, N, Breedt, J, Ebrahim, I, Ellis, G, Fulat, M, van Rensburg, Dj, Raal, F, van Dyk, C, Vally, T, van der Walt, E, Kotzé, H, Landman, C, Tayob, M, Caixas, A, García, Lr, Fernandez Cruz, A, Gil Extremera, B, Grijalvo, Om, Plana, N, Fuentes, F, Valdivielso, P, Fraile, B, Borgencrantz, B, Larnefeldt, H, Tengmark, Bo, Eriksson, M, Olsson Önerud, Å, Amalyan, W, Dyadyk, O, Koval, O, Kushnir, M, Svintsitskiy, A, Kovalyov, O, Bondarchuk, O, Tashchuk, V, Barna, O, Prokhorov, O, Karpenko, O, Stanciu, D, Pawa, R, Balaji, H, Doig, F, Harvey, P, Ranganath, L, Massalski, W, Hassanin, H, Timmis, H, Pavel Knox, I, Abdulhakim, E, Oyesile, B, Horvathova, V, Donnachie, H, Kondagunta, V, Shaw, H, Thomas, H, Kadr, H, Gunstone, A, Lip, G, Ellery, A, Kerrane, J, Sarker, A, Wong, Yk, Soran, H, Maw, K, Andersen, J, Blair Britt, L, Huffman, C, Kivitz, A, Marple, R, Patron, A, Schear, M, Allegar, N, Awasty, V, Casanova, R, Chaykin, L, Cohen, L, Collins, H, Collins, G, Elkin, G, Reyes, H, Feld, L, Fuller, G, Glover, R, Greenwald, J, Herrod, J, Kaye, W, Kimmel, M, Kolettis, E, Lakin, G, Lorch, D, Palatnik, M, Patel, R, Reichman, A, Rohlf, J, Shockey, G, Shore, K, Radin, D, Alvarado, O, Bellingar, B, Egelhof, R, Mcknight, T, Plevin, S, Pritchard, J, Reddy, R, Velazquez, F, Bolster, E, Broker, R, Butuk, D, Cheung, D, Cohen, K, Golden, G, Murray, A, Naccarato, T, Uusinarkaus, K, Pudi, K, Graff, A, Blumberg, V, Dunn, F, Toth, P, Anspach, R, Chuang, R, Meli, J, Nevins, B, Wayne, J, Schmidt, L, Levinsky, D, Rubino, J, Shealy, N, Torres, D, West, J, Jain, R, Vardi, G, Singh, N, Thew, S, Lo, E, Heitner, J, Gerber, J, Malik, A, Weinstein, D, Prashad, R, Koren, M, Ghitis, A, David, W, Reis, G, Kinzfogl, G, Haught, H, Kantaros, L, O'Dea, D, Weiss, D, Kassas, S, Hunter, J, Mollod, M, Khan, N, Henderson, D, Gatien, L, Schramm, R, Madder, R, Voyce, S, Nadar, V, Stich, M, Kumar, M, Black, R, Treasure, C, Lebeis, M, Mccullough, P, Lepor, N, Moriarty, P, Waxler, A, Talreja, D, Gen, M, Dohad, S, East, C, Conrad, G, Asbill, B, Roberts, J, Robinson, J, Zarich, S, Davis, B, Krolick, M, Sherman, H, and Thompson, P.
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- 2015
8. Efficacy and safety of a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with its components given alone: results of a phase 3, open-label, randomised, 26-week, treat-to-target trial in insulin-naive patients with type 2 diabetes
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Gough, S. C., Bode, B., Woo, V., Rodbard, H. W., Linjawi, S., Poulsen, P., Damgaard, L. H., Buse, J. B., NN9068 3697 trial investigators, Donnelly, T, Gerstman, M, Linjawi, S, Park, K, Roberts, A, Shaw, Je, Wu, T, Aggarwal, N, Bowering, K, Chouinard, G, Deyoung, P, Dumas, R, Elliott, Tg, Frechette, A, Giguere, N, Gottesman, I, Ho, K, Kohli, S, Teitelbaum, I, Tytus, R, Wharton, S, Woo, V, Hellsten, T, Kuusela, M, Sarti, C, Strand, J, Valli, K, Erlinger, R, Goelz, S, Hauser, Kh, Hilgenberg, J, Kaiser, M, Marck, C, Merfort, F, Milek, K, Paschen, B, Rose, L, Schlecht, K, Wenzl Bauer, V, Dudas, M, Fulop, G, Harcsa, E, Kerenyi, Z, Szőcs, A, Takacs, R, Babu, T, Bandgar, Tr, Bantwal, G, Bhagwat, Nm, Chatterjee, S, Jain, Sm, John, M, Kale, S, Kanungo, Ak, Kumar, A, Kumar, H, Kumar, Sn, Lodha, S, Majumder, A, Mithal, A, Murthy, S, Sethi, Bk, Shah, P, Sharma, Sk, Sivagnanam, N, Velu, S, Viswanathan, V, Yajnik, Cs, Byrne, M, O'Brien, T, Aimaretti, G, Baroni, Mg, D'Amico, E, Dotta, Francesco, Giordano, C, Sforza, A, Tonolo, G, Bebakar, Wm, Kamaruddin, Na, Hussein, Z, Mumtaz, M, Sothiratnam, R, Gonzalez Galvez, G, Hernandez, Pa, Grineva, E, Kalashnikova, Mf, Kulkova, P, Krasilnikova, Ee, Kondrachenko, S, Kunitsyna, Ma, Poley, M, Sardinov, R, Vorokhobina, Nv, Yurievna, M, Zhdanova, Ea, Zhukova, La, Dalan, R, Khoo, Ey, Sum, Cf, Cizova, M, Martinka, E, Schroner, Z, Teplanova, M, Tomasova, L, Biermann, E, Dulabh, R, Khutsoane, Dt, Komati, Sm, Makan, Ha, Mayet, L, Mitha, Ea, Padayachee, T, Pillay, S, Reddy, J, Snyman, Hh, Siddique, N, Trokis, J, Bobillo, Er, de la Cuesta, C, Fernández, Mr, González, As, De Teresa Parreño, L, Raya, Pm, de la Torre ML, Torres, Jf, Sheu, Wh, Sun, Jh, Yang, Cy, Deerochanawong, C, Phornphutkul, M, Suwanwalaikorn, S, Sriwijitkamol, A, Clark, J, Downie, P, Evans, P, Furlong, N, Gough, S, Harper, R, Harvey, Jn, Khan, A, Leese, G, Mckinnon, C, Narendran, P, Patterson, C, Raymond, F, Singhal, P, Smith, P, Viljoen, A, Willis, T, Acampora, M, Agaiby, Jm, Ahmed, I, Allison, Jr, Altamirano, D, Anderson, Mw, Andrawis, N, Aroda, Vr, Ballard, Tv, Beavins, J, Bedel, Gw, Bernstein, R, Blaze, K, Bode, Bw, Bononi, Pl, Broker, Re, Buse, Jb, Butuk, Dj, Camiscoli, Dj, Canadas, R, Castorino, K, Cathcart, H, Cha, G, Chang, A, Chappel, Cm, Cheema, C, Chenore, M, Cheung, D, Christensen, J, Chu, Jw, Chuck, L, Cohen, Cd, Cohen, K, Cho, Mh, Rivera Colon, L, Condit, J, Corbett, B, Pearlstein, R, Cox, Wr, Daboul, Ny, Deatkine, D, Dunn, Lj, Ellison, Hs, Feldman, Bn, Fidelholtz, J, First, B, Fishman, N, Fogarty, Cm, Fraser, Nj, Gabra, N, Gaona, Re, Gerety, G, Gilman, Rm, Gonte, Ws, Gottschlich, Gm, Grant, Dm, Hewitt, M, Hollander, P, House, Ba, Huffman, D, Jain, Rk, Johnson, G, Jones, Sw, Kayne, Dm, Kimmel, Ma, Klonoff, D, Knight, H, Koontz, D, Kutner, Me, Lenhard, Jm, Liss, Jl, Litchfield, Wr, Lubin, B, Lucas, Kj, Lynn, L, Lyons, Tj, Macadams, Mr, Mach, Mq, Maletz, L, Mariano, Hg, Mayeda, So, Pratley, Re, Madder, R, Martinez, Gj, Mcgarity WC Jr, Mckenzie, Wc, Meisner, Cr, Montenegro, C, Moran, Je, Morawski, Ej, Moretto, Tj, Mudaliar, Sr, Murray, Av, Myers, L, Odugbesan, Ao, Olivarez, E, Pangtay, D, Patel, Mb, Patel, Nr, Patel, R, Perdomo, A, Pritchett, Kl, Rasmussen, B, Reed, Jc, Reeves, Ml, Reichman, A, Rhee, C, Rice, Lc, Risser, J, Rodbard, Hw, Rosen, R, Rosenstock, J, Ryan, Eh, Schreiman, Rc, Scott, Rb, Selagamsetty, Mr, Shaughnessy, J, Silver, R, Simon, Hj, Snyder, B, Soufer, J, Stegemoller, Rk, Sugimoto, D, Thurman, J, Tolia, Kk, Wagner, R, Wahlen, J, Webster, De, Weisbrot, Aj, Whittier, F, Winkle, Pj, Woolley, Jh, Yeoman, G, Zemel, Lr, Smith, Bp, Philis Tsimikas, A, Weissman, P, and Kurland Wise, J.
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Insulin degludec ,Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Urology ,Type 2 diabetes ,law.invention ,Endocrinology ,Randomized controlled trial ,law ,Glucagon-Like Peptide 1 ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Glycated Hemoglobin ,Liraglutide ,business.industry ,Insulin ,Middle Aged ,medicine.disease ,Metformin ,Insulin, Long-Acting ,Drug Combinations ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Female ,business ,Pioglitazone ,medicine.drug - Abstract
A fixed-ratio combination of the basal insulin analogue insulin degludec and the glucagon-like peptide-1 (GLP-1) analogue liraglutide has been developed as a once-daily injection for the treatment of type 2 diabetes. We aimed to compare combined insulin degludec-liraglutide (IDegLira) with its components given alone in insulin-naive patients.In this phase 3, 26-week, open-label, randomised trial, adults with type 2 diabetes, HbA1c of 7-10% (inclusive), a BMI of 40 kg/m(2) or less, and treated with metformin with or without pioglitazone were randomly assigned (2:1:1) to daily injections of IDegLira, insulin degludec, or liraglutide (1·8 mg per day). IDegLira and insulin degludec were titrated to achieve a self-measured prebreakfast plasma glucose concentration of 4-5 mmol/L. The primary endpoint was change in HbA1c after 26 weeks of treatment, and the main objective was to assess the non-inferiority of IDegLira to insulin degludec (with an upper 95% CI margin of 0·3%), and the superiority of IDegLira to liraglutide (with a lower 95% CI margin of 0%). This study is registered with ClinicalTrials.gov, number NCT01336023.1663 adults (mean age 55 years [SD 10], HbA1c 8·3% [0·9], and BMI 31·2 kg/m(2) [4·8]) were randomly assigned, 834 to IDegLira, 414 to insulin degludec, and 415 to liraglutide. After 26 weeks, mean HbA1c had decreased by 1·9% (SD 1·1) to 6·4% (1·0) with IDegLira, by 1·4% (1·0) to 6·9% (1·1) with insulin degludec, and by 1·3% (1·1) to 7·0% (1·2) with liraglutide. IDegLira was non-inferior to insulin degludec (estimated treatment difference -0·47%, 95% CI -0·58 to -0·36, p0·0001) and superior to liraglutide (-0·64%, -0·75 to -0·53, p0·0001). IDegLira was generally well tolerated; fewer participants in the IDegLira group than in the liraglutide group reported gastrointestinal adverse events (nausea 8·8 vs 19·7%), although the insulin degludec group had the fewest participants with gastrointestinal adverse events (nausea 3·6%). We noted no clinically relevant differences between treatments with respect to standard safety assessments, and the safety profile of IDegLira reflected those of its component parts. The number of confirmed hypoglycaemic events per patient year was 1·8 for IDegLira, 0·2 for liraglutide, and 2·6 for insulin degludec. Serious adverse events occurred in 19 (2%) of 825 patients in the IDegLira group, eight (2%) of 412 in the insulin degludec group, and 14 (3%) of 412 in the liraglutide group.IDegLira combines the clinical advantages of basal insulin and GLP-1 receptor agonist treatment, resulting in improved glycaemic control compared with its components given alone.Novo Nordisk.
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- 2014
9. (652) - A Single Center Experience of the Impella RP in Acute Right Ventricular Failure
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Proudfoot, A., Mulder, A., Maragiri, S., Pardington, E., Osip, E., Ten Brock, T., VanOosterhout, S., Madder, R., and Lee, S.
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- 2018
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10. The Relationship Between Coronary Arterial Plaque Burden and Lipid Pools: Histological Validation Using Near-Infrared Spectroscopy and Intravascular Ultrasound
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Andrews, J., primary, Puri, R., additional, Madden, S., additional, Madder, R., additional, Muller, J., additional, Wolski, K., additional, Kataoka, Y., additional, Uno, K., additional, King, K., additional, Tuzcu, E., additional, Kapadia, S., additional, and Nicholls, S., additional
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- 2013
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11. Linear Free Energy Relationships Implicate Three Modes of Binding for Fluoroaromatic Inhibitors to a Mutant of Carbonic Anhydrase II
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Doyon, J. B., Hansen, E. A. M., Kim, C.-Y., Chang, J. S., Christianson, D. W., Madder, R. D., Voet, J. G., Baird, T. A., Jr., Fierke, C. A., and Jain, A.
- Abstract
Linear free energy relationships between binding affinity and hydrophobicity for a library of fluoroaromatic inhibitors of F131V carbonic anhydrase II (CA) implicate three modes of interaction. X-ray crystal structures suggest that F131 interacts with fluoroaromatic inhibitors, while P202, on the opposite side of the active site cleft, serves as the site of the hydrophobic contact in the case of the F131V mutant. 2-Fluorinated compounds bind more tightly, perhaps due to the field effect of the nearby fluorine on the acidity of the amide proton. - Published
- 2000
12. Latest Developments in Robotic Percutaneous Coronary Interventions.
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Khokhar AA, Marrone A, Bermpeis K, Wyffels E, Tamargo M, Fernandez-Avilez F, Ruggiero R, Złahoda-Huzior A, Giannini F, Zelias A, Madder R, Dudek D, and Beyar R
- Abstract
Since the first robotic-assisted percutaneous coronary intervention procedure (R-PCI) was performed in 2004, there has been a steady evolution in robotic technology, combined with a growth in the number of robotic installations worldwide and operator experience. This review summarises the latest developments in R-PCI with a focus on developments in robotic technology, procedural complexity, tele-stenting and training methods, which have all contributed to the global expansion in R-PCI., Competing Interests: Disclosure: RM has received grants, consulting fees, speaker fees and travel expenses for meetings from Corindus. EF and EW have received consulting fees from Siemens and Corindus Vascular Robotics. AZH and DD have received speaker fees from Siemens. RB has holds stocks in Cordiguide, Medhub AI and Cardiac Success. AZ has received a grant from Siemens and Corindus Vascular Robotics. All other authors have no conflicts of interest to declare., (Copyright © The Author(s), 2023. Published by Radcliffe Group Ltd.)
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- 2023
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13. SCAI Publications Committee Manual of Standard Operating Procedures: 2022 Update.
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Szerlip M, Al-Azizi K, Alasnag M, Ando T, Ang L, Bartel RC, Batlivala S, Brott B, Davidson L, Dehghani P, Elmariah S, Eng MH, Garcia S, Giri J, Goldsweig AM, Gordon BM, Guerrero ME, Herrmann HC, Jneid H, Kar S, Lansky A, Lata K, Madan M, Madder R, Rymer J, Senerth E, Smith T, Tehrani BN, and Messenger JC
- Abstract
Evidence-based recommendations for clinical practice are intended to help health care providers and patients make decisions, minimize inappropriate practice variation, promote effective resource use, improve clinical outcomes, and direct future research. SCAI has been engaged in the creation and dissemination of clinical guidance documents since the 1990s. These documents are a cornerstone of the Society's education, advocacy, and quality improvement initiatives. The Publications Committee is charged with the oversight of SCAI's clinical documents program and has published the first iteration of this manual of standard operating procedures in 2019 to ensure consistency, methodological rigor, and transparency in the development and endorsement of the Society's documents. The manual has been updated based on feedback from the implementation of the original version to add specificity and expand the breadth of available document formats. The manual is intended for reference by the Publications Committee, document writing groups, external collaborators, SCAI representatives, peer reviewers, and anyone seeking information about the SCAI documents program., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2022 Published by Elsevier Inc. on behalf of the Society for Cardiovascular Angiography and Interventions Foundation.)
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- 2022
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14. Remote robotic endovascular thrombectomy for acute ischaemic stroke.
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Singer J, VanOosterhout S, and Madder R
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Background: In acute ischaemic stroke, endovascular thrombectomy (ET) significantly reduces disability compared with thrombolytic therapy, but access to ET is currently limited. Leveraging telerobotic technology to disseminate neurosurgical expertise could increase access to ET. This proof-of-concept evaluation was performed to determine whether remote robotic ET (RRET), wherein an offsite neurosurgeon and an onsite interventional cardiologist collaboratively use telerobotics to perform ET, is technically feasible., Methods: An ex vivo model of RRET was constructed by establishing a network connection between a robotic drive in a simulation laboratory and a robotic control unit 5 miles away. Using onsite assistance from an interventional cardiologist in the simulation laboratory, an offsite neurosurgeon used the robotic controls to attempt RRET on a fluid-filled silicone model of human vasculature containing simulated thrombus material in the left middle cerebral artery (MCA)., Results: From the offsite location 5 miles away, the neurosurgeon used the robotic system to successfully navigate a guidewire from the carotid artery to simulated thrombus in the MCA. Under the direction of the neurosurgeon, the onsite interventional cardiologist then successfully manually advanced an aspiration catheter over the guidewire to the thrombus, removed the guidewire and performed aspiration., Conclusions: In this proof-of-concept evaluation, the technical feasibility of RRET was demonstrated in an ex vivo model and was collaboratively performed by an offsite neurosurgeon and an onsite interventional cardiologist. This report supports the design of future studies to determine if RRET could be used to increase access to ET for patients with acute ischaemic stroke., Competing Interests: Competing interests: JS: consulting fees, proctoring fees and speaker honoraria Stryker, proctoring fees Medtronic, speaker honoraria Ceronovus, speaker honoraria Penumbra, and educational fees Nico. RM: research support, speaker honoraria and consulting fees Corindus, A Siemens Healthineers Company., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2021
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15. Cardiac Catheterization Laboratory Volume Changes During COVID-19-Findings from a Cardiovascular Fellows Consortium.
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Kadavath S, Mohan J, Ashraf S, Kassier A, Hawwass D, Madan N, Salehi N, Bernardo M, Mawri S, Rehman KA, Ya'qoub L, Strobel A, Dixon SR, Siraj A, Messenger J, Spears JR, Lopez-Candales A, Madder R, Bailey SR, Alaswad K, Kim MC, Safian RD, and Alraies MC
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- Betacoronavirus, COVID-19, Data Collection, Humans, Pandemics, SARS-CoV-2, Social Media, Cardiac Catheterization trends, Coronavirus Infections epidemiology, Pneumonia, Viral epidemiology
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- 2020
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16. OCT-NIRS Imaging for Detection of Coronary Plaque Structure and Vulnerability.
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Muller J and Madder R
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A combination optical coherence tomography and near-infrared spectroscopy (OCT-NIRS) coronary imaging system is being developed to improve the care of coronary patients. While stenting has improved, complications continue to occur at the stented site and new events are caused by unrecognized vulnerable plaques. An OCT-NIRS device has potential to improve secondary prevention by optimizing stenting and by identifying vulnerable patients and vulnerable plaques. OCT is already in widespread use world-wide to optimize coronary artery stenting. It provides automated lumen detection and can identify features of coronary plaques not accurately identified by angiography or intravascular ultrasound. The ILUMIEN IV study, to be completed in 2022, will determine if OCT-guided stenting will yield better clinical outcomes than angiographic guidance alone. While the superb spatial resolution of OCT enables the identification of many plaque structural features, the detection by OCT of lipids, an important component of vulnerable plaques, is limited by suboptimal specificity and interobserver agreement. In contrast, NIRS has been extensively validated for lipid-rich plaque detection against the gold-standard of histology and is the only FDA-approved method to identify coronary lipids. Studies in patients have demonstrated that NIRS detects lipid in culprit lesions causing coronary events. In 2019, the positive results of the prospective Lipid-Rich Plaque Study led to FDA approval of NIRS for detection of high-risk plaques and patients. The complementarity of OCT for plaque structure and NIRS for plaque composition led to the sequential performance of NIRS and OCT imaging in patients. NIRS identified lipid while OCT determined the thickness of the cap over the lipid pool. The positive results obtained with OCT and NIRS imaging led to development of a prototype combined OCT-NIRS catheter that can provide co-registered OCT and NIRS data in a single pullback. The data will provide structural and chemical information likely to improve stenting and deliver more accurate identification of vulnerable plaques and vulnerable patients. More precise diagnosis will then lead to OCT-NIRS guided treatment trials to improve secondary prevention. Success in secondary prevention will then facilitate development of improved primary prevention with invasive imaging and effective treatment of patients identified by non-invasive methods., (Copyright © 2020 Muller and Madder.)
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- 2020
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17. Techniques and best practices for optical coherence tomography: a practical manual for interventional cardiologists.
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Lopez JJ, Arain SA, Madder R, Parekh N, Shroff AR, and Westerhausen D
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- Angioplasty, Balloon, Coronary methods, Cardiology standards, Coronary Stenosis therapy, Female, Humans, Male, Practice Guidelines as Topic, Radiography, Interventional standards, Sensitivity and Specificity, Tomography, Optical Coherence standards, Coronary Stenosis diagnosis, Radiography, Interventional methods, Stents, Tomography, Optical Coherence methods
- Abstract
Optical coherence tomography (OCT) is a novel intracoronary imaging modality that utilizes near-infrared light to provide information regarding lesion length and severity, vessel lumen diameter, plaque morphology, as well as the opportunity for stent procedure guidance and follow-up. While analogous to intravascular ultrasound (IVUS), the specific imaging properties, including significantly higher resolution, and technical specifications of OCT offer the ability for intracoronary diagnostic and interventional procedure guidance roles that require a thorough understanding of the technology. We provide coronary interventionalist's a user's guide to OCT, focusing on techniques and approaches to optimize imaging, with a focus on efficiency, safety and strategies for effective imaging., (© 2014 Wiley Periodicals, Inc.)
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- 2014
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18. Efficacy and safety of fixed combinations of irbesartan/hydrochlorothiazide in older vs younger patients with hypertension uncontrolled with monotherapy.
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Cushman WC, Neutel JM, Saunders E, Bakris GL, Ferdinand KC, Ofili EO, Sowers JR, Madder R, and Weber MA
- Subjects
- Age Factors, Aged, Aged, 80 and over, Antihypertensive Agents adverse effects, Biphenyl Compounds adverse effects, Drug Therapy, Combination, Female, Health Status Indicators, Humans, Hydrochlorothiazide adverse effects, Irbesartan, Male, Middle Aged, Prospective Studies, Tetrazoles adverse effects, Treatment Outcome, Antihypertensive Agents therapeutic use, Biphenyl Compounds therapeutic use, Hydrochlorothiazide therapeutic use, Hypertension drug therapy, Tetrazoles therapeutic use
- Abstract
Subgroup analysis of the Irbesartan/Hydrochlorothiazide Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial evaluated the efficacy and safety of irbesartan/hydrochlorothiazide (HCTZ) fixed combinations in patients aged 65 years or older with uncontrolled systolic blood pressure (SBP) after >or= 4 weeks of antihypertensive monotherapy. The INCLUSIVE trial was a prospective, open-label, single-arm trial carried out in 119 sites. Of 844 patients completing placebo treatment, 212 were aged 65 years or older. Participants received treatment with placebo (4-5 weeks), HCTZ 12.5 mg (2 weeks), irbesartan/HCTZ 150/12.5 mg (8 weeks), and then irbesartan/HCTZ 300/25 mg (8 weeks). From baseline to week 18 (n=184, intent-to-treat population), mean change in SBP was -23.0+/-13.3 mm Hg (P<.001) and diastolic BP (DBP) was -10.9+/-7.7 mm Hg (P<.001). Mean SBP/DBP at study end was 134.0+/-14.7/75.1+/-8.4 mm Hg, and SBP, DBP, and SBP/DBP goal was achieved in 73%, 96%, and 72% of patients, respectively. Irbesartan/HCTZ combination therapy allowed SBP goal attainment in 73% of patients aged 65 years or older whose hypertension was previously uncontrolled with antihypertensive monotherapy.
- Published
- 2008
- Full Text
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