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1. Prediction of acute respiratory disease in current and former smokers with and without COPD.

Author

Bowler, Russell P, Kim, Victor, Regan, Elizabeth, Williams, André AA, Santorico, Stephanie A, Make, Barry J, Lynch, David A, Hokanson, John E, Washko, George R, Bercz, Peter, Soler, Xavier, Marchetti, Nathaniel, Criner, Gerard J, Ramsdell, Joe, Han, MeiLan K, Demeo, Dawn, Anzueto, Antonio, Comellas, Alejandro, Crapo, James D, Dransfield, Mark, Wells, J Michael, Hersh, Craig P, MacIntyre, Neil, Martinez, Fernando, Nath, Hrudaya P, Niewoehner, Dennis, Sciurba, Frank, Sharafkhaneh, Amir, Silverman, Edwin K, van Beek, Edwin JR, Wilson, Carla, Wendt, Christine, and Wise, Robert A

Subjects
Humans, Respiratory Tract Diseases, Pulmonary Disease, Chronic Obstructive, Acute Disease, Hospitalization, Incidence, Proportional Hazards Models, Risk Factors, Longitudinal Studies, Follow-Up Studies, Smoking, Quality of Life, Aged, Middle Aged, United States, Female, Male, Clinical Research, Lung, Chronic Obstructive Pulmonary Disease, Respiratory, Good Health and Well Being, Clinical Sciences, Respiratory System
Abstract

BackgroundThe risk factors for acute episodes of respiratory disease in current and former smokers who do not have COPD are unknown.MethodsEight thousand two hundred forty-six non-Hispanic white and black current and former smokers in the Genetic Epidemiology of COPD (COPDGene) cohort had longitudinal follow-up (LFU) every 6 months to determine acute respiratory episodes requiring antibiotics or systemic corticosteroids, an ED visit, or hospitalization. Negative binomial regression was used to determine the factors associated with acute respiratory episodes. A Cox proportional hazards model was used to determine adjusted hazard ratios (HRs) for time to first episode and an acute episode of respiratory disease risk score.ResultsAt enrollment, 4,442 subjects did not have COPD, 658 had mild COPD, and 3,146 had moderate or worse COPD. Nine thousand three hundred three acute episodes of respiratory disease and 2,707 hospitalizations were reported in LFU (3,044 acute episodes of respiratory disease and 827 hospitalizations in those without COPD). Major predictors included acute episodes of respiratory disease in year prior to enrollment (HR, 1.20; 95% CI, 1.15-1.24 per exacerbation), airflow obstruction (HR, 0.94; 95% CI, 0.91-0.96 per 10% change in % predicted FEV1), and poor health-related quality of life (HR, 1.07; 95% CI, 1.06-1.08 for each 4-unit increase in St. George's Respiratory Questionnaire score). Risks were similar for those with and without COPD.ConclusionsAlthough acute episode of respiratory disease rates are higher in subjects with COPD, risk factors are similar, and at a population level, there are more episodes in smokers without COPD.

Published
2014

2. Rivaroxaban for Thromboprophylaxis after Hospitalization for Medical Illness

Author

Spyropoulos A. C., Ageno W., Albers G. W., Elliott C. G., Halperin J. L., Hiatt W. R., Maynard G. A., Steg P. G., Weitz J. I., Suh E., Spiro T. E., Barnathan E. S., Raskob G. E., Douketis J., Turpie A. G., Schulman S., Kearon C., Linkins L. A., Schellong S., Bauer K., Geerts W., Roberts R., Casais P., Gallus A., Karrasch J., Eichinger-Hasenauer S., Krivenchuk V., Hadzovic-Dzuvo A., Trbojevic S., Lopes R., Mincheva V., Carrier M., Dennis R., Tudoric N., Spinar J., Nielsen H., Marandi T., Shaburishvili T., Beyer-Westendorf J., Vardas P., Boda Z., Brenner B., Piovella F., Krievins D., Petrauskiene B., Dejanova-Ilijevska V., Virgen Carrillo L. R., Middeldorp S., Castillo Leon R. P., Torbicki A., Saraiva de Sousa M., Dorobantu M., Militaru C., Yavelov I., Vuckovic B., Reuter H., Basson M., Monreal M., Kucukoglu S., Parkhomenko A., Alikhan R., Rosenberg D., Yusen R., Khorana A., Tapson V., Pollack C., Hazelrigg M., Jure H., Alvarisqueta A., Cartasegna L., Hominal M., Cursack G., Alzogaray M., Maillo M., Parody M., Caccavo A., Dran R. D., Muntaner J. A., Casas M., Schmidberg J., Sarjanovich R., Gabito A., Garrido M., Amuchastegui M., Fernandez A., Loureyro J., Giumelli C., Heazlewood V., Colquhoun D., White H., Sabet A., Bowler S., Carroll P., Khalafallah A., Baker R., Hedger S., Simpson F. G., Jackson D., Chong B., Siostrzonek P., Gary T., Hoppe U., Dosta N., Prystrom A., Gorokhovsky S., Yanushko V., Skrahin A., Kulik A., Maslianski B., Yakubtsevich R., Timkin I., Moguchaya O., Tanaskovic N., Miljkovic S., Stojkovic S., Kovacevic-Preradovic T., Jovic D., Basagic E., Radjen M., Mutapcic M., Rizvanovic-Vojic E., Galic K., Terzic I., Pojskic B., Stevanovic D., Cehajic M., Rech R., Annichino-Bizzacchi J., Stelmach R., Blanco D., Castro I., Backes L. M., Saraiva J. F., Ramacciotti E., de Barros e Silva P. G. M., Reis G., Moreira Vieira E., Leaes P., Zimmermann S., Van Bellen B., Precoma D., Luiz Silvestrini T., Hernandes M. E., Kyoleyan M., Kalinova T., Tiholov R., Petrov I., Mihov A., Chompalova B., Velikov C., Pencheva G., Atanasov P., Raev D., Kinova E., Peltegov V., Marchev S., Siulemezova S., Ayryanova I. D., Grigorov M., Naydenova I., Koteva N., Dimov B., Runev N., Getov D., Metev H., Donchev K., Taseva M., Hadzhieva A., Benov H., Stoyanov M., Tisheva-Gospodinova S., Mihaylova N., Abadzhiev S., Atzev B., Georgiev R., Mollov M., Stoikov A., Mazhdrakov G., Karastanev K., Dube F., Roth S., Mansour S., Wu C., Dolan S., Pesant Y., Pietrangelo M., Dresser G., Kahn S., Kruisselbrink R., Cadena Bonfanti A., Botero R., Quintero Ossa A., Poveda C. M., Cedano J., Gomez Isaza L., Villaquiran Torres C., Gomez Mesa J., Vargas Alonso R., Espinosa D., Rodriguez J. M., Sanchez G., Accini Mendoza J. L., Gomez Florez C. C., Cuervo Millan F., Pesek K., Horvat D., Fuckar K., Ruzic A., Ostricki B., Knezevic A., Breitenfeld T., Laganovic M., Samodol A., Sikic J., Starcevic B., Babic Z., Samarzija M., Milas K., Votocek S., Kvapil M., Kolman P., Bindas P., Simon V., Adamek T., Svobodova J., Gergely L., Lastuvka J., Macel I., Navratil K., Gregor P., Lacnak B., Janousek J., Kellnerova I., Hulinsky V., Matusek Z., Prucek L., Dunaj M., Pirchala M., Vencour D., Pavolko M., Gorican K., Fiksa J., Tuxen C., Meyer C., Suppli Ulrik C., Uuetoa T., Otarishvili N., Khintibidze I., Emukhvari N., Kipiani Z., Gochitashvili D., Mamatsashvili M., Megreladze I., Paposhvili K., Agladze R., Eradze Z., Chelidze K., Lominadze S., Chukhrukidze A., Chumburidze V., Metreveli S., Danelia V., Orjonikidze S., Kobulia B., Nikolaishvili G., Gvenetadze R., Melia A., Tsinamdzgvrishvili B., Sekhniashvili M., Sikharulidze I., Meuser M., Licka M., Rauch-Kroehnert U., Graf K., Brachmann J., Akin I., Toumbis M., Vassilikos V., Konstantinides S., Steiropoulos P., Gogos C., Andrikopoulos G., Parthenakis F., Karydi P., Tsivgoulis G., Mertzanos G., Olympios C., Karapanayiotides T., Paraskevopoulou E., Kifnidis K., Hahalis G., Skoutelis A., Vadikolias K., Nyirati G., Nagy L., Matoltsy A., Komoly S., Lippai J., Kiss K., Toth K., Pozsegovits K., Kiraly C., Bereczki D., Zolyomi S., Szakal I., Pall D., Futo L., Forster T., Lovasz O., Papp A., Kiraly Z., Pozsonyi Z., Hajko E., Kristof P., Lakatos F., Ples Z., Kirschner R., Lupkovics G., Timar G., Pinter I., Kristof T., Kis E., Kovacs A., Jakab G., Palinkas A., Muller G., Turi T., Horvath C., Kondakor I., Csanyi A., Frankfurter Z., Gurzo M., Gafter-Gvili A., Kuchuk M., Azzam Z., Elis A., Halabi M., Hussein O., Blum A., Tsoran-Rosenthal I., Lishner M., Hochberg-Klein S., Caraco Y., Atar S., Elias N., Gavish D., Butnaru A., Cosmi F., Garbelotto R., Giorgi Pierfranceschi M., Simioni L., Gronda E., Pesci A., D'Angelo A., Fedele F., Ghirarduzzi A., Piovaccari G., Lembo G., Ria L., Monaco G. L., Brunelli C., Tosetto A., Capucci A., Zanatta N., Pistolesi M., Mazzi V., Testa S., Scherillo M., Di Biase M., Antonicelli R., Lodigiani C., Nassiacos D., Viksne I., Lapkovska Z., Rancane G., Sime I., Pontaga N., Eglite R., Puzule S., Smolova R., Butkiene Z., Bagdonas A., Raugaliene R., Norkiene S., Norviliene R., Basijokiene V., Stonkus S., Griskeviciene V., Miskiniene A., Norvaisiene R., Skripkauskiene I., Jovkovska-Kaeva B., Kochovska-Kamchevska N., Antovski A., Nechevska L., Celeska V., Ilievska-Poposka B., Kostojchinoska M., Donchovska S., Kedev S., Kuzmanovski I., Bushletikj O., Stojchev S., Bakrachevski N., Kuzmanovska B., Angusheva T., Llamas Esperon G., Valdez Lopez H., Medina Pech C., Cortes Hernandez M., Virgen Carrillo L., Gans S., Smulders S., Swart H., Boersma W., Goosens M., Hovens M., Semplonius G., Sohne M., Lema Osores J., Salas Perez M. D., Rodriguez A., Rios Oliva C., Cotrina R., Berrospi Argandona P., Toce Yanez L., Chavez Ayala C., Mirek-Bryniarska E., Goch A., Skucha W., Skorski M., Miekus P., Szyszka A., Piotrowski G., Gniot J., Czerski T., Debich P., Zaluska R., Bebenek W., Wozakowska-Kaplon B., Sciborski R., Ilkowski J., Wojnowski P., Uscinska E., Gaciong Z., Bonek R., Sobkowicz B., Berkowski P., Bejgier K., Polonski L., Kosior D., Lata S., Kolodziej P., Gessek J., Kachel T., Talalaj M., Musial J., Lewczuk J., Krysiak W., Kucharski L., Wysokinski A., Minc P., Martinez J., Gregorio T., Almeida F., Monteiro P., Stanciulescu G., Mercea C. D., Iosipescu L. C., Ciobotaru V., Crisu D., Burca M., Tudoran M., Savu A., Negrean V., Cojocaru C., Minescu B., Popa V., Blajan D., Nastase-Melicovici D., Fruntelata A., Barbulescu S., Lukinyh L., Akhunova S., Vishneva E., Semenova I., Nikolaev K. Y., Shaydyuk O., Nilk R., Shalnev V., Apartsin K., Goloshchekin B. M., Shpagina L., Khlevchuk T., Arkhipov M., Malygin A., Shvarts Y., Khaisheva L., Popov D., Kobalava Z., Lipchenko A., Shapovalova Y., Zrazhevsky K., Greshnova I., Maslova N., Karabenenko A., Shogenov Z., Budankova E., Barbarash O., Uspenskiy Y., Kosmacheva E., Berns S., Kostenko V., Zateyshchikov D., Vishnevsky A., Boldueva S., Podzolkov V., Sergeeva E., Grinshtein Y., Khrustalev O., Bugrova O., Repin A., Andreev D., Petrovic P., Boskovic Matic T., Apostolovic S., Lazic Z., Stankovic D., Stankovic A., Mitov V., Sofronic D., Kopitovic I., Zdravkovic V., Joksimovic Z., Lazovic N., Petrovic-Stanojevic N., Ilic A., Vujadinovic O., Pencic-Popovic B., Andjelkovic N., Sekularac N., Hinic S., Radjen G., Zivkovic A., Putnikovic B., Ivanov I., Babic R., Van Zyl L., Hobson B., Engelbrecht J., Mitha I., Siebert H., Jacobson B., Breedt J., Prozesky H., Ntsekhe M., Bayat J., Ellis G., Tarr G., Adler D., Van Dyk C., Ismail S. M., Spargo C. E., Abdool-Gaffar M., Saaiman J., Venter K., Lorente Aroca M. L., Fernandez Portales F., Pedrajas Navas J., Rodriguez Botaro A., Santa Cruz Siminiani A., Lopez Reyes R., Bisbe i Company J., Piedecausa Selfa M., Velasco Garrido J., Sobrino-Martinez J., Munoz Delgado G., Sala Llinas E., Blanco Coronado J., Almenar Bonet L., Vida Gutierrez M., Sanchez Lora F., Sanchez Martinez R., Calderon E. J., Villalta Blanch J., De la Hera Galarza J. M., Bustamante Ruiz A., Garcia-Fuster M. J., Ripoll Vera T., Alvarez-Sala Walter L., Todoli Parra J. A., Diaz Fernandez J., Bosa Ojeda F., Pellicer-Ciscar C., Jara Palomares L., Quiles Granado J., Trigo Bautista A., Ruiz Bustillo S., Ordi Ros J., Tolosa-Vilella C., Marin Ortuno F., Garcia Sanchez F., Barba Martin R., Segovia Cubero J., Cuervas-Mons Martinez V., Galan Montejano M., Lopez Meseguer M., Sener Comert S., Koksal N., Tertemiz K., Ernam D., Dursun A. B., Yildiz O., Rudenko L., Abrahamovych O., Goloborodko A., Holovchenko N., Kulyk A., Yagensky A., Batushkin V., Zolotaikina V., Kozyolkin O., Faynyk A., Maslovskyy V., Petrovskyy R., Koshlia V., Chopey I., Burmak I., Malynovsky Y., Voronkov L., Karpenko O., Dziublyk O., Godlevska O., Borovyk V., Bezrodna L., Serik S., Ovsyannikova N., Vynnychenko L., Kopytsya M., Rudkovskiy V., Grishyna O., Vyshnyvetskyy I., Prystupa L., Tseluyko V., Perepeliuk M., Koval O., Sychov O., Church A., Goudie A., Elliott M., Ferguson C., Welker J., Kao C. K., Bhagwat R., Serota H., Bozorgchami H., Nambiar R., Spilseth S., Bhagwath G., Syed F., Morrow L., Updegrove J., Bercz P., Kambo V., Henderson D., Wright P., Dang N., Nadar V., Jaffrani N., El-Shahawy M., Grossman C. H., Pearle J., Weinstein D., Galanis T. P., Gazmuri R., Kastelic R., Martinez R., Laman D., Macchiavelli A., Kmetzo J., Thurm C., Kayembe T., Chandrashekhar Y., Bassetti D., Jaoude P., Williams H., Dewhurst R., Naqvi S., Burr J., Rodriguez-Cintron W., Jeanfreau R., Kosinski E., Ndukwu I. M., Sotolongo C., Daboul N., Wilmer C., Simon P., Tak T., Rees C., Gupta N., Lerner R., Graffagnino C., Reed R. M., Alford C. M., Mody F., Wellmon B., Hamroff G., Rajan R., Kaatz S., OMÜ, Spyropoulos, A, Ageno, W, Albers, G, Elliott, C, Halperin, J, Hiatt, W, Maynard, G, Steg, P, Weitz, J, Suh, E, Spiro, T, Barnathan, E, Raskob, G, Douketis, J, Turpie, A, Schulman, S, Kearon, C, Linkins, L, Schellong, S, Bauer, K, Geerts, W, Roberts, R, Casais, P, Gallus, A, Karrasch, J, Eichinger-Hasenauer, S, Krivenchuk, V, Hadzovic-Dzuvo, A, Trbojevic, S, Lopes, R, Mincheva, V, Carrier, M, Dennis, R, Tudoric, N, Spinar, J, Nielsen, H, Marandi, T, Shaburishvili, T, Beyer-Westendorf, J, Vardas, P, Boda, Z, Brenner, B, Piovella, F, Krievins, D, Petrauskiene, B, Dejanova-Ilijevska, V, Virgen Carrillo, L, Middeldorp, S, Castillo Leon, R, Torbicki, A, Saraiva de Sousa, M, Dorobantu, M, Militaru, C, Yavelov, I, Vuckovic, B, Reuter, H, Basson, M, Monreal, M, Kucukoglu, S, Parkhomenko, A, Alikhan, R, Rosenberg, D, Yusen, R, Khorana, A, Tapson, V, Pollack, C, Hazelrigg, M, Jure, H, Alvarisqueta, A, Cartasegna, L, Hominal, M, Cursack, G, Alzogaray, M, Maillo, M, Parody, M, Caccavo, A, Dran, R, Muntaner, J, Casas, M, Schmidberg, J, Sarjanovich, R, Gabito, A, Garrido, M, Amuchastegui, M, Fernandez, A, Loureyro, J, Giumelli, C, Heazlewood, V, Colquhoun, D, White, H, Sabet, A, Bowler, S, Carroll, P, Khalafallah, A, Baker, R, Hedger, S, Simpson, F, Jackson, D, Chong, B, Siostrzonek, P, Gary, T, Hoppe, U, Dosta, N, Prystrom, A, Gorokhovsky, S, Yanushko, V, Skrahin, A, Kulik, A, Maslianski, B, Yakubtsevich, R, Timkin, I, Moguchaya, O, Tanaskovic, N, Miljkovic, S, Stojkovic, S, Kovacevic-Preradovic, T, Jovic, D, Basagic, E, Radjen, M, Mutapcic, M, Rizvanovic-Vojic, E, Galic, K, Terzic, I, Pojskic, B, Stevanovic, D, Cehajic, M, Rech, R, Annichino-Bizzacchi, J, Stelmach, R, Blanco, D, Castro, I, Backes, L, Saraiva, J, Ramacciotti, E, de Barros e Silva, P, Reis, G, Moreira Vieira, E, Leaes, P, Zimmermann, S, Van Bellen, B, Precoma, D, Luiz Silvestrini, T, Hernandes, M, Kyoleyan, M, Kalinova, T, Tiholov, R, Petrov, I, Mihov, A, Chompalova, B, Velikov, C, Pencheva, G, Atanasov, P, Raev, D, Kinova, E, Peltegov, V, Marchev, S, Siulemezova, S, Ayryanova, I, Grigorov, M, Naydenova, I, Koteva, N, Dimov, B, Runev, N, Getov, D, Metev, H, Donchev, K, Taseva, M, Hadzhieva, A, Benov, H, Stoyanov, M, Tisheva-Gospodinova, S, Mihaylova, N, Abadzhiev, S, Atzev, B, Georgiev, R, Mollov, M, Stoikov, A, Mazhdrakov, G, Karastanev, K, Dube, F, Roth, S, Mansour, S, Wu, C, Dolan, S, Pesant, Y, Pietrangelo, M, Dresser, G, Kahn, S, Kruisselbrink, R, Cadena Bonfanti, A, Botero, R, Quintero Ossa, A, Poveda, C, Cedano, J, Gomez Isaza, L, Villaquiran Torres, C, Gomez Mesa, J, Vargas Alonso, R, Espinosa, D, Rodriguez, J, Sanchez, G, Accini Mendoza, J, Gomez Florez, C, Cuervo Millan, F, Pesek, K, Horvat, D, Fuckar, K, Ruzic, A, Ostricki, B, Knezevic, A, Breitenfeld, T, Laganovic, M, Samodol, A, Sikic, J, Starcevic, B, Babic, Z, Samarzija, M, Milas, K, Votocek, S, Kvapil, M, Kolman, P, Bindas, P, Simon, V, Adamek, T, Svobodova, J, Gergely, L, Lastuvka, J, Macel, I, Navratil, K, Gregor, P, Lacnak, B, Janousek, J, Kellnerova, I, Hulinsky, V, Matusek, Z, Prucek, L, Dunaj, M, Pirchala, M, Vencour, D, Pavolko, M, Gorican, K, Fiksa, J, Tuxen, C, Meyer, C, Suppli Ulrik, C, Uuetoa, T, Otarishvili, N, Khintibidze, I, Emukhvari, N, Kipiani, Z, Gochitashvili, D, Mamatsashvili, M, Megreladze, I, Paposhvili, K, Agladze, R, Eradze, Z, Chelidze, K, Lominadze, S, Chukhrukidze, A, Chumburidze, V, Metreveli, S, Danelia, V, Orjonikidze, S, Kobulia, B, Nikolaishvili, G, Gvenetadze, R, Melia, A, Tsinamdzgvrishvili, B, Sekhniashvili, M, Sikharulidze, I, Meuser, M, Licka, M, Rauch-Kroehnert, U, Graf, K, Brachmann, J, Akin, I, Toumbis, M, Vassilikos, V, Konstantinides, S, Steiropoulos, P, Gogos, C, Andrikopoulos, G, Parthenakis, F, Karydi, P, Tsivgoulis, G, Mertzanos, G, Olympios, C, Karapanayiotides, T, Paraskevopoulou, E, Kifnidis, K, Hahalis, G, Skoutelis, A, Vadikolias, K, Nyirati, G, Nagy, L, Matoltsy, A, Komoly, S, Lippai, J, Kiss, K, Toth, K, Pozsegovits, K, Kiraly, C, Bereczki, D, Zolyomi, S, Szakal, I, Pall, D, Futo, L, Forster, T, Lovasz, O, Papp, A, Kiraly, Z, Pozsonyi, Z, Hajko, E, Kristof, P, Lakatos, F, Ples, Z, Kirschner, R, Lupkovics, G, Timar, G, Pinter, I, Kristof, T, Kis, E, Kovacs, A, Jakab, G, Palinkas, A, Muller, G, Turi, T, Horvath, C, Kondakor, I, Csanyi, A, Frankfurter, Z, Gurzo, M, Gafter-Gvili, A, Kuchuk, M, Azzam, Z, Elis, A, Halabi, M, Hussein, O, Blum, A, Tsoran-Rosenthal, I, Lishner, M, Hochberg-Klein, S, Caraco, Y, Atar, S, Elias, N, Gavish, D, Butnaru, A, Cosmi, F, Garbelotto, R, Giorgi Pierfranceschi, M, Simioni, L, Gronda, E, Pesci, A, D'Angelo, A, Fedele, F, Ghirarduzzi, A, Piovaccari, G, Lembo, G, Ria, L, Monaco, G, Brunelli, C, Tosetto, A, Capucci, A, Zanatta, N, Pistolesi, M, Mazzi, V, Testa, S, Scherillo, M, Di Biase, M, Antonicelli, R, Lodigiani, C, Nassiacos, D, Viksne, I, Lapkovska, Z, Rancane, G, Sime, I, Pontaga, N, Eglite, R, Puzule, S, Smolova, R, Butkiene, Z, Bagdonas, A, Raugaliene, R, Norkiene, S, Norviliene, R, Basijokiene, V, Stonkus, S, Griskeviciene, V, Miskiniene, A, Norvaisiene, R, Skripkauskiene, I, Jovkovska-Kaeva, B, Kochovska-Kamchevska, N, Antovski, A, Nechevska, L, Celeska, V, Ilievska-Poposka, B, Kostojchinoska, M, Donchovska, S, Kedev, S, Kuzmanovski, I, Bushletikj, O, Stojchev, S, Bakrachevski, N, Kuzmanovska, B, Angusheva, T, Llamas Esperon, G, Valdez Lopez, H, Medina Pech, C, Cortes Hernandez, M, Gans, S, Smulders, S, Swart, H, Boersma, W, Goosens, M, Hovens, M, Semplonius, G, Sohne, M, Lema Osores, J, Salas Perez, M, Rodriguez, A, Rios Oliva, C, Cotrina, R, Berrospi Argandona, P, Toce Yanez, L, Chavez Ayala, C, Mirek-Bryniarska, E, Goch, A, Skucha, W, Skorski, M, Miekus, P, Szyszka, A, Piotrowski, G, Gniot, J, Czerski, T, Debich, P, Zaluska, R, Bebenek, W, Wozakowska-Kaplon, B, Sciborski, R, Ilkowski, J, Wojnowski, P, Uscinska, E, Gaciong, Z, Bonek, R, Sobkowicz, B, Berkowski, P, Bejgier, K, Polonski, L, Kosior, D, Lata, S, Kolodziej, P, Gessek, J, Kachel, T, Talalaj, M, Musial, J, Lewczuk, J, Krysiak, W, Kucharski, L, Wysokinski, A, Minc, P, Martinez, J, Gregorio, T, Almeida, F, Monteiro, P, Stanciulescu, G, Mercea, C, Iosipescu, L, Ciobotaru, V, Crisu, D, Burca, M, Tudoran, M, Savu, A, Negrean, V, Cojocaru, C, Minescu, B, Popa, V, Blajan, D, Nastase-Melicovici, D, Fruntelata, A, Barbulescu, S, Lukinyh, L, Akhunova, S, Vishneva, E, Semenova, I, Nikolaev, K, Shaydyuk, O, Nilk, R, Shalnev, V, Apartsin, K, Goloshchekin, B, Shpagina, L, Khlevchuk, T, Arkhipov, M, Malygin, A, Shvarts, Y, Khaisheva, L, Popov, D, Kobalava, Z, Lipchenko, A, Shapovalova, Y, Zrazhevsky, K, Greshnova, I, Maslova, N, Karabenenko, A, Shogenov, Z, Budankova, E, Barbarash, O, Uspenskiy, Y, Kosmacheva, E, Berns, S, Kostenko, V, Zateyshchikov, D, Vishnevsky, A, Boldueva, S, Podzolkov, V, Sergeeva, E, Grinshtein, Y, Khrustalev, O, Bugrova, O, Repin, A, Andreev, D, Petrovic, P, Boskovic Matic, T, Apostolovic, S, Lazic, Z, Stankovic, D, Stankovic, A, Mitov, V, Sofronic, D, Kopitovic, I, Zdravkovic, V, Joksimovic, Z, Lazovic, N, Petrovic-Stanojevic, N, Ilic, A, Vujadinovic, O, Pencic-Popovic, B, Andjelkovic, N, Sekularac, N, Hinic, S, Radjen, G, Zivkovic, A, Putnikovic, B, Ivanov, I, Babic, R, Van Zyl, L, Hobson, B, Engelbrecht, J, Mitha, I, Siebert, H, Jacobson, B, Breedt, J, Prozesky, H, Ntsekhe, M, Bayat, J, Ellis, G, Tarr, G, Adler, D, Van Dyk, C, Ismail, S, Spargo, C, Abdool-Gaffar, M, Saaiman, J, Venter, K, Lorente Aroca, M, Fernandez Portales, F, Pedrajas Navas, J, Rodriguez Botaro, A, Santa Cruz Siminiani, A, Lopez Reyes, R, Bisbe i Company, J, Piedecausa Selfa, M, Velasco Garrido, J, Sobrino-Martinez, J, Munoz Delgado, G, Sala Llinas, E, Blanco Coronado, J, Almenar Bonet, L, Vida Gutierrez, M, Sanchez Lora, F, Sanchez Martinez, R, Calderon, E, Villalta Blanch, J, De la Hera Galarza, J, Bustamante Ruiz, A, Garcia-Fuster, M, Ripoll Vera, T, Alvarez-Sala Walter, L, Todoli Parra, J, Diaz Fernandez, J, Bosa Ojeda, F, Pellicer-Ciscar, C, Jara Palomares, L, Quiles Granado, J, Trigo Bautista, A, Ruiz Bustillo, S, Ordi Ros, J, Tolosa-Vilella, C, Marin Ortuno, F, Garcia Sanchez, F, Barba Martin, R, Segovia Cubero, J, Cuervas-Mons Martinez, V, Galan Montejano, M, Lopez Meseguer, M, Sener Comert, S, Koksal, N, Tertemiz, K, Ernam, D, Dursun, A, Yildiz, O, Rudenko, L, Abrahamovych, O, Goloborodko, A, Holovchenko, N, Kulyk, A, Yagensky, A, Batushkin, V, Zolotaikina, V, Kozyolkin, O, Faynyk, A, Maslovskyy, V, Petrovskyy, R, Koshlia, V, Chopey, I, Burmak, I, Malynovsky, Y, Voronkov, L, Karpenko, O, Dziublyk, O, Godlevska, O, Borovyk, V, Bezrodna, L, Serik, S, Ovsyannikova, N, Vynnychenko, L, Kopytsya, M, Rudkovskiy, V, Grishyna, O, Vyshnyvetskyy, I, Prystupa, L, Tseluyko, V, Perepeliuk, M, Koval, O, Sychov, O, Church, A, Goudie, A, Elliott, M, Ferguson, C, Welker, J, Kao, C, Bhagwat, R, Serota, H, Bozorgchami, H, Nambiar, R, Spilseth, S, Bhagwath, G, Syed, F, Morrow, L, Updegrove, J, Bercz, P, Kambo, V, Henderson, D, Wright, P, Dang, N, Nadar, V, Jaffrani, N, El-Shahawy, M, Grossman, C, Pearle, J, Weinstein, D, Galanis, T, Gazmuri, R, Kastelic, R, Martinez, R, Laman, D, Macchiavelli, A, Kmetzo, J, Thurm, C, Kayembe, T, Chandrashekhar, Y, Bassetti, D, Jaoude, P, Williams, H, Dewhurst, R, Naqvi, S, Burr, J, Rodriguez-Cintron, W, Jeanfreau, R, Kosinski, E, Ndukwu, I, Sotolongo, C, Daboul, N, Wilmer, C, Simon, P, Tak, T, Rees, C, Gupta, N, Lerner, R, Graffagnino, C, Reed, R, Alford, C, Mody, F, Wellmon, B, Hamroff, G, Rajan, R, and Kaatz, S

Subjects
Male, medicine.medical_specialty, Aftercare, Aged, Double-Blind Method, Drug Administration Schedule, Factor Xa Inhibitors, Female, Hemorrhage, Humans, Kaplan-Meier Estimate, Middle Aged, Patient Discharge, Rivaroxaban, Treatment Outcome, Venous Thromboembolism, Venous Thrombosis, Hospitalization, Medicine (all), 030204 cardiovascular system & hematology, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Medical illness, Internal medicine, Hospital discharge, Medicine, Venous Thrombosi, 030212 general & internal medicine, Thromboprophylaxis, business.industry, General Medicine, medicine.disease, Venous thrombosis, Increased risk, rivaroxaban, thromboprophylaxis, medical illness, business, Venous thromboembolism, Factor Xa Inhibitor, Human, medicine.drug
Abstract

Zateyshchikov, Dmitry A/0000-0001-7065-2045; Vyshnyvetskyy, Ivan/0000-0001-7228-3052; Bustillo, Sonia Ruiz/0000-0002-6074-914X; Maslovskyi, Valentyn/0000-0001-5184-1799; Ruzic, Alen/0000-0001-5031-2975; Nikolaev, Konstantin/0000-0003-4601-6203; Musial, Jacek/0000-0002-8994-0036; Malynovsky, Yaroslav V/0000-0002-9118-1104; Tsivgoulis, Georgios/0000-0002-0640-3797; Maslovskyi, Valentyn/0000-0001-5184-1799; Grinshtein, Yury/0000-0001-8847-235X; Shpagina, Lyubov/0000-0003-0871-7551; Yildiz, Oznur/0000-0002-5379-6829; Marchev, Sotir/0000-0001-9250-510X; Weitz, Jeffrey/0000-0002-1092-7550; Apartsin, Konstantin A/0000-0003-0577-9001; Reis, Gilmar/0000-0002-4847-1034; Baker, Ross/0000-0002-2728-6788; Koziolkin, Olexandr/0000-0001-9878-5798; Barbarash, Olga/0000-0002-4642-3610; Sala-Llinas, Ernest/0000-0002-6499-1638; Gallus, Alexander/0000-0001-7347-9989; lodigiani, corrado/0000-0002-9152-9385; Kosmacheva, Elena/0000-0001-8600-0199; Ramacciotti, Eduardo/0000-0002-5735-1333; Khorana, Alok/0000-0002-9509-0998; Giorgi-Pierfranceschi, Matteo/0000-0002-7988-9652; Torbicki, Adam/0000-0003-3475-8832; Abragamovic, Orest/0000-0001-6862-6809; Jara-Palomares, Luis/0000-0002-4125-3376; Prozesky, Hans/0000-0001-9715-3449; Andreev, Denis/0000-0002-0276-7374; Cuervas-Mons Martinez, Valentin/0000-0003-3086-9463; Apostolovic, Svetlana/0000-0001-9015-297X; Gregorio, Tiago/0000-0002-0131-9430; Sanchez Martinez, Rosario/0000-0003-0408-3029; Antonicelli, Roberto/0000-0002-5921-1828; Konstantinides, Stavros/0000-0001-6359-7279; Karapanayiotides, Theodoros/0000-0002-2357-7967; Repin, Alexey/0000-0001-7123-0645 WOS: 000445020900006 PubMed: 30145946 BACKGROUND Patients who are hospitalized for medical illness remain at risk for venous thromboembolism after discharge, but the role of extended thromboprophylaxis in the treatment of such patients is a subject of controversy. METHODS In this randomized, double-blind trial, medically ill patients who were at increased risk for venous thromboembolism on the basis of a modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) score of 4 or higher (scores range from 0 to 10, with higher scores indicating a higher risk of venous thromboembolism) or a score of 2 or 3 plus a plasma n-dimer level of more than twice the upper limit of the normal range (defined according to local laboratory criteria) were assigned at hospital discharge to either once-daily rivaroxaban at a dose of 10 mg (with the dose adjusted for renal insufficiency) or placebo for 45 days. The primary efficacy outcome was a composite of symptomatic venous thromboembolism or death due to venous thromboembolism. The principal safety outcome was major bleeding. RESULTS Of the 12,024 patients who underwent randomization, 12,019 were included in the intention-to-treat analysis. The primary efficacy outcome occurred in 50 of 6007 patients (0.83%) who were given rivaroxaban and in 66 of 6012 patients (1.10%) who were given placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.52 to 1.09; P=0.14). The prespecified secondary outcome of symptomatic nonfatal venous thromboembolism occurred in 0.18% of patients in the rivaroxaban group and 0.42% of patients in the placebo group (hazard ratio, 0.44; 95% CI, 0.22 to 0.89). Major bleeding occurred in 17 of 5982 patients (0.28%) in the rivaroxaban group and in 9 of 5980 patients (0.15%) in the placebo group (hazard ratio, 1.88; 95% CI, 0.84 to 4.23). CONCLUSIONS Rivaroxaban, given to medical patients for 45 days after hospital discharge, was not associated with a significantly lower risk of symptomatic venous thromboembolism and death due to venous thromboembolism than placebo. The incidence of major bleeding was low. Janssen Research and Development; Daiichi SankyoDaiichi Sankyo Company Limited; Portola; Boehringer IngelheimBoehringer Ingelheim; JanssenJohnson & Johnson USAJanssen Biotech Inc; BayerBayer AG; BMS PfizerPfizer; Aspen; Sanofi; University of Cincinnati and Spectrum Health; PfizerPfizer; ATLAS Group (Colorado Prevention Center); Johnson JohnsonJohnson & Johnson USA; Ortho-McNeil-JanssenJohnson & Johnson USAJanssen Biotech Inc; Bayer/JanssenJohnson & Johnson USAJanssen Biotech IncBayer AG; MerckMerck & Company; AmgenAmgen Supported by Janssen Research and Development.r Dr. Spyropoulos reports receiving advisory board fees from Daiichi Sankyo and Portola, grant support, consulting fees, and advisory board fees from Boehringer Ingelheim and Janssen, consulting fees and advisory board fees from Bayer, and a stipend from ATLAS Group (Colorado Prevention Center); Dr. Ageno, receiving grant support and advisory board fees from Bayer and BMS Pfizer and advisory board fees from Portola, Daiichi Sankyo, Aspen, Boehringer Ingelheim, and Sanofi; Dr. Albers, receiving consulting fees from Bayer; Dr. Elliott, receiving fees for serving on a steering committee from Bayer and lecture fees from the University of Cincinnati and Spectrum Health; Dr. Halperin, receiving consulting fees from Boehringer Ingelheim, Daiichi Sankyo, Pfizer, ATLAS Group (Colorado Prevention Center), Johnson & Johnson, and Ortho-McNeil-Janssen; Dr. Hiatt, receiving grant support from Janssen and Bayer; Dr. Steg, receiving grant support and fees for serving on a steering committee from Bayer/Janssen, grant support and lecture fees from Merck, grant support, consulting fees, lecture fees, and fees for serving as cochair of the ODYSSEY outcomes trial and the SCORED trial from Sanofi, grant support and fees for serving as chair of the CLARIFY registry from Servier, consulting fees and fees for serving on the executive steering committee for the REDUCE IT trial from Amarin, consulting fees and lecture fees from Amgen, consulting fees, lecture fees, and fees for critical event committee work from Bristol-Myers Squibb, fees for serving on the executive steering committee of the REDUAL PCI trial from Boehringer Ingelheim, fees for critical event committee work from Pfizer, consulting fees and fees for serving on the executive steering committee for the PARADISE MI trial from Novartis, consulting fees from Regeneron and Lilly, and consulting fees and fees for serving as cochair of the THEMIS trial from AstraZeneca; Dr. Weitz, receiving consulting fees and honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Ionis, Janssen, Merck, Novartis, Pfizer and Portola; Dr. Suh and Dr. Barnathan, being employed by Janssen Research and Development and owning stock in Johnson & Johnson; Dr. Spiro, being employed by and owning shares in Bayer U.S.; and Dr. Raskob, receiving consulting fees from Bayer, BMS, Boehringer Ingelheim, Eli Lilly, Portola, and Novartis and consulting fees and honoraria from Daiichi Sankyo and Pfizer. No other potential conflict of interest relevant to this article was reported.

Published
2018

3. Extended-Duration Betrixaban Reduces the Risk of Stroke Versus Standard-Dose Enoxaparin Among Hospitalized Medically Ill Patients

Author

Legkonogov, O., Ramacciotti, E., Mikhailova, E., Koryk, V., Adzerikho, I., Schoenerr, H., Mathies, R., Konig, J., Huber, K., Rubinfeld, A., Finfer, S., Manenti, E., Bott, M., Blessing, E., Beyer-Westendorf, J., Coughlin, P., Baker, R., Poy, C., Dengler, T., Parody, M., Oliva, M., Macin, S., Jure, H., Ferrari, A. E., Dziewas, R., Genth-Zotz, S., Hamann, F., Horacek, T., Klimpe, S., Mitkovskaya, N., Kroning, R., Lapp, H., Lawall, H., Licka, M., Rizos, T., Tiefenbacher, C., Weimar, C., Alkonyi, B., Falukozy, J., Futo, L., Katona, A., Berrouschot, J., Kirschner, R., Amann, B., Paposhvili, K., Pagava, Z., Kristof, P., Lakatos, F., Laszlo, Z., Freire, A., Lupkovics, G., Megreladze, I., Kobulia, B., Khintibidze, I., Khabeishvili, G., Datikashvili-David, I., Simoneau, G., Merkely, B., Andras, C. Nagy, Nemeth, L., Papp, A., Soltesz, P., Fiss, E., Schmidt, J., Roy, P-M., Quere, I., Proust, A., Pottier, P., Pernod, G., Payot, L., Bizzacchi, J. Annichino, Lienart, F., Paleiron, N., Montaclair, K., Mismetti, P., Messas, E., Lacroix, P., Grange, C., Falvo, N., El Kouri, D., Decoulx, E., Debourdeau, P., De Geeter, G., Brisot, D., Belhassane, A., Aquilanti, S., Agraou, B., Vikman, S., Tatlisumak, T., Saarinen, J., Kaaja, R., Honkaniemi, J., Airaksinen, J., Uuetoa, T., Lember, M., Urhammer, S., Tuxen, C., Storgaard, M., Lassen, M., Christensen, H., Vyhnanek, M., Vejvoda, J., Spacek, R., Reiterer, P., Podpera, I., Mikulova, J., Lang, P., Jajtner, P., Hubac, J., Horny, I., Holaj, R., Herold, M., Havelka, J., Francek, L., Dusek, J., Dunaj, M., Cizek, V., Chochola, J., Chlumsky, J., Cermak, O., Skerk, V., Vagic, J. Sikic, Marusic, S., Knezevic, A., Kalinic-Grgorinic, H., Jakopovic, M., Francetic, I., Ciglenecki, N., Car, S., Butkovic-Soldo, S., Cardenas, S. Potthoff, Lazcano, M. Opazo, Alarcon, M. Arias, Verreault, S., Provencher, S., Pearce, M., Le Gal, G., Douketis, J., Dhar, A., Tokmakova, M., Todorov, G., Syulemzova, S., Raymuno, S., Rocha, A., Dimov, B., Grigorov, M., Kalpachki, R., Kamenova, Z., Bello, F., Harrington, Robert A., Bandman, Olga, Kostadinova, M., Milanova, M., Dive, A., Pencheva, G., Sudar, Z., Szabo, G., Szegedi, N., Timar, G., Valco, J., Delforge, M., Vertes, A., Efrati, S., Elias, M., Gafter, A., Nazliel, BİJEN, Hayek, T., Hussein, O., Lishner, M., Lugassy, G., Cerveri, I., D'Angelo, A., De Pellegrin, A., Imberti, D., Landolfi, R., Runev, N., Lembo, G., Lodigiani, C., Moia, M., Molteni, M., Mumoli, N., Novo, S., Orlandini, F., Stoeva, N., Parisi, R., Pizzini, A., Pomero, F., Salvi, A., Schenone, A., Gold, Alex, Visona, A., Martinova, V., Pontaga, N., Rozitis, V., Stukena, I., Alekniene, B., Basijokiene, V., Butkiene, Z., Griskeviciene, V., Naudziunas, A., Stoyanov, M., Norvaisiene, R., Norviliene, R., Petrauskiene, R., Poskiene, R., Susinskiene, D., Valavicius, A., Castillo Leon, R., Pimanov, S., Polonetsy, L., Pereyra, R. Cotrina, Karlo, L. Farjardo, Horna, M., Soroka, N., Salas, M., Yanez, L. Toche, Fryze, W., Gaciong, Z., Gniot, J., Gorecka, D., Gruenpeter, P., Grzelakowski, P., Jastrzebski, D., Kucharski, L., Mirek-Bryniarska, E., Pulkowski, G., Sobkowicz, B., Sulik, P., Walasek, L., Blockmans, D., Waldemar, K., Wrzesinski, K., Balogh, Z. E., Bojinca, M., Marin, I., Musetescu, R., Podoleanu, C., Popescu, M., Stamate, S., Stanciulescu, G., Vida-Simiti, L., Abashev, A., Andreev, D., Apartsin, K., Arkhipov, M., Averkov, O., Barbarash, O., Belskaya, G., Bogdanov, E., Boldueva, S., Chefranova, Z., Dovgalevskiy, Y., Ershova, O., Goloshchekin, B., Khachatryan, N., Klein, G., Kobalava, Z., Kosmacheva, E., Kostenko, V., Malygin, A., Martynenko, T., Martynenko, V., Maslova, N., Mordovin, V., Nikolaev, K., Nilk, R., Popov, D., Privalova, E., Reshetko, O., Shapovalova, Y., Shpagina, L., Shvarts, Y., Simanenkov, V., Solovyov, O., Vishneva, E., Vishnevskiy, A., Apostolovic, S., Celic, V., Ilic, S., Kovacevic-Kuzmanovic, A., Miloradovic, V., Bodikova, S., Cervenakova, A., Dvorak, M., Herman, O., Hrubon, A., Kokles, M., Krastev, G., Payer, J., Prokop, D., Spisakova, M., Adler, D., Basson, M., Breedt, J., Engelbrecht, J., Mitha, I., Van Dyk, C., Alvarez Sala, L. A., Barbagelata Lopez, C., Bisbe, J., Castro Guardiola, A., Cepeda, J. M., Cereto, F., Diaz Santos, E., Ferrer, R., Gomez Cerezo, J., Hernandez, Adrian F., Gonzales-Porras, J. R., Grandes, J., Cohen, Alexander T., Gibson, C. Michael, Chi, Gerald, Halaby, Rim, Korjian, Serge, Daaboul, Yazan, Jain, Purva, Arbetter, Douglas, Goldhaber, Samuel Z., Hull, Russel, Jimenez, D., Mellibovsky, L., Richart, C., Riera, A., Trujillo, J., Vargas Nunez, J. A., Villalta, J., Akgul, O., Guneri, S., Kilichesmez, K., Kirma, C., Kutluk, H., Okumus, G., Tigen, K., Topcuoglu, M., Tuncay, E., Abrahamovych, O., Batushkin, V., Brozhyk, J., Burmak, I., Godlevska, O., Goloborodko, A., Goloborodko, B., Goncharova, Y., Gryb, V., Karpenko, O., Kopytsya, M., Zakai, N., Yousef, K., Wichman, T., Whitman, B., Welker, J., Welch, M., Warner, A., Updegrove, J., Tuck, M., Stoltz, S., Sokol, S., Sharma, S., Shammas, N., Saba, F., Rodriguez, W., Rees, C., Rastogi, P., Rajan, R., Quintana, O., Pullman, J., Pratt, R., Pineda, L., Pearl, R., Parthiban, K., Overcash, J., Ortel, T., Ohaju, V., Nadar, V., Mittal, M., Milling, T., McLaren, G., Margolis, B., Mahal, S., Macchiavelli, A., Lopez, J., Lerner, R., Kung, M., Kouras, F., Kazimir, M., Kao, C-K., Kabler, H., Ioachimescu, O., Hazelrigg, M., Hamad, A., Haidar, A., Hahn, B., Goytia-Leos, D., Gaggin, H., Fulmer, J., Koshlia, V., Fraiz, J., Krakhmalova, O., Fermann, G., Farley, B., Doshi, A., Dhingra, R., Cornell, J., Concha, M., Clark, C., Chang, H., Carman, T., Bidair, M., Bercz, P., Bastani, A., Barney, J., Baker, S., Anderson, C., Amin, M., Almasri, E., Natarajan, I., McCollum, C., MacCallum, P., Davis, M., Body, R., Yagensky, A., Voronkov, L., Vishnivestsky, I., Vakaliuk, I., Ursol, G., Tseluyko, V., Kyrychenko, I., Svyshchenko, Y., Svyridova, I., Ryabichenko, T., Rudenko, L., Reshotko, D., Perepeliuk, M., Parkhomenko, O., Nikonov, V., Maslovaskyi, V., Malynovsky, Y., Sergeeva, E., and Kolman, P.

Subjects
Male, medicine.medical_specialty, Pyridines, Intracranial Hemorrhages, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Medical illness, Physiology (medical), medicine, Humans, 030212 general & internal medicine, Enoxaparin, Intensive care medicine, Stroke, Aged, business.industry, Anticoagulants, Venous Thromboembolism, medicine.disease, Thrombosis, chemistry, Betrixaban, Benzamides, Emergency medicine, Female, Cardiology and Cardiovascular Medicine, business, Complication, Venous thromboembolism
Abstract

Background: Stroke is a morbid and potentially mortal complication among patients hospitalized with acute medical illness. The potential of extended-duration thromboprophylaxis with the factor Xa inhibitor betrixaban to reduce the risk of stroke compared with standard-dose enoxaparin in this population was assessed in this retrospective APEX trial substudy (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban). Methods: Hospitalized acutely medically ill subjects (n=7513) were randomized in a double-dummy double-blind fashion to either extended-duration oral betrixaban (80 mg once daily for 35–42 days) or standard-dose subcutaneous enoxaparin (40 mg once daily for 10±4 days) for venous thromboprophylaxis. Stroke events were adjudicated by an independent, blinded event adjudication committee. Results: The mean age of study participants was 76 years; 45% were male; 13% had had a stroke; and 45% had congestive heart failure. There were fewer all-cause strokes (0.54% versus 0.97%; relative risk [RR]=0.56; 95% confidence interval, 0.32–0.96; P =0.032; adjusted RR=0.43%; number needed to treat=233) and ischemic strokes (0.48% versus 0.91%; RR=0.53; 95% confidence interval, 0.30–0.94; P =0.026; adjusted RR=0.43%; number needed to treat=233) among patients treated with betrixaban versus enoxaparin through 77 days of follow-up. Among high-risk subjects, those with congestive heart failure or ischemic stroke as their index event, betrixaban reduced the risk of all-cause stroke (0.72% versus 1.48%; RR=0.49; 95% confidence interval, 0.26–0.90; P =0.019; adjusted RR=0.76%; number needed to treat=132) and ischemic stroke (0.63% versus 1.38%; RR=0.45; 95% confidence interval, 0.24–0.87; P =0.014; adjusted RR=0.75%; number needed to treat=134) compared with enoxaparin. Conclusions: Among hospitalized medically ill patients, extended-duration betrixaban significantly reduced all-cause stroke and ischemic stroke through 77 days of follow-up Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01583218.

Published
2017
Full Text
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4. Comparison of Fatal or Irreversible Events With Extended-Duration Betrixaban Versus Standard Dose Enoxaparin in Acutely III Medical Patients: An APEX Trial Substudy

Author

Gibson, C. M., Korjian, S., Chi, G., Daaboul, Y., Jain, P., Arbetter, D., Goldhaber, S. Z., Hull, R., Hernandez, A. F., Lopes, R. D., Gold, A., Cohen, A. T., Harrington, R. A., Bello, F., Ferrari, A. E., Jure, H., Macin, S., Oliva, M., Parody, M., Poy, C., Baker, R., Colquhoun, D., Coughlin, P., Finfer, S., Hammerschlag, G., Rubinfeld, A., Huber, K., Konig, J., Mathies, R., Pilger, E., Schoenerr, H., Adzerikho, I., Koryk, V., Mikhailova, E., Mitkovskaya, N., Pimanov, S., Polonetsy, L., Soroka, N., Blockmans, D., Delforge, M., Dive, A., Lienart, F., Motte, S., Annichino Bizzacchi, J., Fiss, E., Freire, A., Manenti, E., Ramacciotti, E., Raymuno, S., Rocha, A., Saraiva, J. F., Dimov, B., Grigorov, M., Kalpachki, R., Kamenova, Z., Kostadinova, M., Milanova, M., Mincheva, V., Pencheva, G., Raev, D., Runev, N., Stoeva, N., Stoyanov, M., Syulemzova, S., Todorov, G., Tokmakova, M., Dhar, A., Douketis, J., Kahn, S., Le Gal, G., Pearce, M., Provencher, S., Verreault, S., Arias Alarcon, M., Olivares Canon, C., Opazo Lazcano, M., Potthoff Cardenas, S., Butkovic-Soldo, S., Car, S., Ciglenecki, N., Francetic, I., Jakopovic, M., Kalinic-Grgorinic, H., Knezevic, A., Malojcic, B., Marusic, S., Sikic Vagic, J., Skerk, V., Cermak, O., Cervinka, P., Chlumsky, J., Chochola, J., Cizek, V., Dunaj, M., Dusek, J., Francek, L., Havelka, J., Herold, M., Holaj, R., Horny, I., Hubac, J., Jajtner, P., Kolman, P., Lang, P., Mayer, O., Mikulova, J., Podpera, I., Reiterer, P., Spacek, R., Vejvoda, J., Vyhnanek, M., Christensen, H., Lassen, M., Storgaard, M., Tuxen, C., Urhammer, S., Lember, M., Marandi, T., Uuetoa, T., Airaksinen, J., Honkaniemi, J., Kaaja, R., Lassila, R., Saarinen, J., Tatlisumak, T., Vikman, S., Agraou, B., Aquilanti, S., Belhassane, A., Brisot, D., De Geeter, G., Debourdeau, P., Decoulx, E., El Kouri, D., Falvo, N., Grange, C., Lacroix, P., Messas, E., Mismetti, P., Montaclair, K., Mottier, D., Paleiron, N., Payot, L., Pernod, G., Pottier, P., Proust, A., Quere, I., Roy, P. -M., Schmidt, J., Simoneau, G., Datikashvili-David, I., Khabeishvili, G., Khintibidze, I., Kobulia, B., Megreladze, I., Pagava, Z., Paposhvili, K., Shaburishvili, T., Amann, B., Berrouschot, J., Beyer-Westendorf, J., Blessing, E., Bott, M., Dengler, T., Diehm, C., Dziewas, R., Genth-Zotz, S., Hamann, F., Horacek, T., Klimpe, S., Kroning, R., Lapp, H., Lawall, H., Licka, M., Rizos, T., Schellong, S., Schmidt-Lucke, J., Singer, C., Tiefenbacher, C., Veltkamp, R., Weimar, C., Zeymer, U., Alkonyi, B., Falukozy, J., Futo, L., Katona, A., Kirschner, R., Kristof, P., Lakatos, F., Laszlo, Z., Lupkovics, G., Merkely, B., Nagy Andras, C., Nemeth, L., Papp, A., Soltesz, P., Sudar, Z., Szabo, G., Szegedi, N., Timar, G., Valco, J., Vertes, A., Efrati, S., Elias, M., Gafter, A., Hayek, T., Hussein, O., Lishner, M., Lugassy, G., Zeltser, D., Ageno, W., Cerveri, I., D'Angelo, A., De Pellegrin, A., Imberti, D., Landolfi, R., Lembo, G., Lodigiani, C., Luisetti, M., Moia, M., Molteni, M., Mumoli, N., Novo, S., Orlandini, F., Parisi, R., Pizzini, A., Pomero, F., Salvi, A., Schenone, A., Visona, A., Krievins, D., Martinova, V., Pontaga, N., Rozitis, V., Stukena, I., Alekniene, B., Bagdonas, A., Basijokiene, V., Butkiene, Z., Griskeviciene, V., Naudziunas, A., Norvaisiene, R., Norviliene, R., Petrauskiene, R., Poskiene, R., Susinskiene, D., Valavicius, A., Castillo Leon, R., Cotrina Pereyra, R., Farjardo Karlo, L., Horna, M., Lema Osores, J., Salas, M., Toche Yanez, L., Fryze, W., Gaciong, Z., Gniot, J., Gorecka, D., Gruenpeter, P., Grzelakowski, P., Jastrzebski, D., Kucharski, L., Mirek-Bryniarska, E., Pulkowski, G., Sobkowicz, B., Sulik, P., Tomkowski, W., Walasek, L., Waldemar, K., Wrzesinski, K., Balogh, Z. E., Bojinca, M., Marin, I., Mot, S., Musetescu, R., Podoleanu, C., Popescu, M., Stamate, S., Stanciulescu, G., Vida-Simiti, L., Abashev, A., Andreev, D., Apartsin, K., Arkhipov, M., Averkov, O., Barbarash, O., Belskaya, G., Bogdanov, E., Boldueva, S., Chefranova, Z., Dovgalevskiy, Y., Ershova, O., Goloshchekin, B., Khachatryan, N., Khurs, E., Klein, G., Kobalava, Z., Kosmacheva, E., Kostenko, V., Malygin, A., Martynenko, T., Martynenko, V., Maslova, N., Mordovin, V., Nikolaev, K., Nilk, R., Panchenko, E., Popov, D., Privalova, E., Reshetko, O., Sergeeva, E., Shapovalova, Y., Shpagina, L., Shvarts, Y., Simanenkov, V., Solovyov, O., Vishneva, E., Vishnevskiy, A., Apostolovic, S., Celic, V., Ilic, S., Kovacevic-Kuzmanovic, A., Miloradovic, V., Tan, R. S., Bodikova, S., Cervenakova, A., Dvorak, M., Gaspar, L., Herman, O., Hrubon, A., Kokles, M., Krastev, G., Payer, J., Prokop, D., Spisakova, M., Adler, D., Basson, M., Breedt, J., Engelbrecht, J., Jacobson, B., Mitha, I., Van Dyk, C., Alvarez Sala, L. A., Barbagelata Lopez, C., Bisbe, J., Castro Guardiola, A., Cepeda, J. M., Cereto, F., Diaz Santos, E., Ferrer, R., Gomez Cerezo, J., Gonzales-Porras, J. R., Grandes, J., Jimenez, D., Martin Loeches, I., Mellibovsky, L., Richart, C., Riera, A., Trujillo, J., Vargas Nunez, J. A., Villalta, J., Akgul, O., Guneri, S., Kilichesmez, K., Kirma, C., Kutluk, H., Nazliel, B., Okumus, G., Ongen, G., Tigen, K., Topcuoglu, M., Tuncay, E., Abrahamovych, O., Batushkin, V., Brozhyk, J., Burmak, I., Godlevska, O., Goloborodko, A., Goloborodko, B., Goncharova, Y., Gryb, V., Karpenko, O., Kopytsya, M., Koshlia, V., Krakhmalova, O., Kyrychenko, I., Legkonogov, O., Malynovsky, Y., Maslovaskyi, V., Nikonov, V., Parkhomenko, O., Perepeliuk, M., Reshotko, D., Rudenko, L., Ryabichenko, T., Svyridova, I., Svyshchenko, Y., Tseluyko, V., Ursol, G., Vakaliuk, I., Vishnivestsky, I., Voronkov, L., Yagensky, A., Body, R., Chandra, D., Davis, M., Kesteven, P., Maccallum, P., Mccollum, C., Natarajan, I., Almasri, E., Amin, M., Anderson, C., Baker, S., Barney, J., Bastani, B. B. A., Bercz, P., Bidair, M., Carman, T., Chang, H., Clark, C., Concha, M., Cornell, J., Dhingra, R., Doshi, A., Ebrahimi, R., Farley, B., Fermann, G., Foster, G., Fraiz, J., Fulmer, J., Gaggin, H., Goytia-Leos, D., Hahn, B., Haidar, A., Hamad, A., Hazelrigg, M., Ioachimescu, O., Johnson, B., Kabler, H., Kao, C. -K., Kazimir, M., Kouras, F., Kung, M., Lerner, R., Lopez, J., Macchiavelli, A., Mahal, S., Margolis, B., Mclaren, G., Milling, T., Mittal, M., Nadar, V., Ohaju, V., Ortel, T., Overcash, J., Parthiban, K., Pearl, R., Pineda, L., Pratt, R., Pullman, J., Quintana, O., Rajan, R., Rastogi, P., Rees, C., Rodriguez, W., Saba, F., Shammas, N., Sharma, S., Sokol, S., Stoltz, S., Subich, D., Tuck, M., Updegrove, J., Warner, A., Welch, M., Welker, J., Whitman, B., Wichman, T., Yousef, K., Yusen, R., and Zakai, N.

Subjects
Male, pulmonary embolism, Time Factors, Pyridines, Intracranial hemorrhage, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Risk Factors, Clinical Studies, Medicine, 030212 general & internal medicine, Myocardial infarction, Original Research, Ischemic stroke, Hazard ratio, Absolute risk reduction, Venous Thromboembolism, Middle Aged, Interventional Cardiology, Pulmonary embolism, Death, myocardial infarction, Treatment Outcome, Cardiovascular Diseases, Anesthesia, Acute Disease, Benzamides, Number needed to treat, Female, Cardiology and Cardiovascular Medicine, Intracranial Hemorrhages, Adult, venous thromboembolism, Hemorrhage, 03 medical and health sciences, Double-Blind Method, death, ischemic stroke, Humans, Enoxaparin, Aged, Proportional Hazards Models, Inpatients, Venous thromboembolism, business.industry, Settore MED/09 - MEDICINA INTERNA, Anticoagulants, Thrombosis, medicine.disease, Clinical trial, chemistry, Betrixaban, business, Acute Coronary Syndromes, intracranial hemorrhage, Factor Xa Inhibitors
Abstract

Background Extended‐duration betrixaban showed a significant reduction in venous thromboembolism in the APEX trial (Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study). Given the variable clinical impact of different efficacy and safety events, one approach to assess net clinical outcomes is to include only those events that are either fatal or cause irreversible harm. Methods and Results This was a post hoc analysis of the APEX trial—a multicenter, double‐blind, randomized controlled trial comparing extended‐duration betrixaban versus standard‐of‐care enoxaparin. A composite of all fatal or irreversible safety (fatal bleeding or intracranial hemorrhage) and efficacy events (cardiopulmonary death, myocardial infarction, pulmonary embolism, and ischemic stroke) was evaluated in a time‐to‐first event analysis. In patients with positive D‐dimer results, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.80% versus 3.54%; hazard ratio, 0.73; absolute risk reduction, 1.26%; number needed to treat, 79 [ P =0.033]) and at study end at 77 days (6.27% versus 4.36%; hazard ratio, 0.70; absolute risk reduction, 1.91%; number needed to treat, 52 [ P =0.005]) versus enoxaparin. In all patients, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.08% versus 2.90%; hazard ratio, 0.71; absolute risk reduction, 1.18%; number needed to treat, 86 [ P =0.006]) and 77 days (5.17% versus 3.64%; hazard ratio, 0.70; absolute risk reduction, 1.53%; number needed to treat, 65 [ P =0.002]). Conclusions Among hospitalized medically ill patients, extended‐duration betrixaban demonstrated an ≈30% reduction in fatal or irreversible ischemic or bleeding events compared with standard‐duration enoxaparin. A total of 65 patients would require treatment with betrixaban to prevent 1 fatal or irreversible event versus enoxaparin. Clinical Trial Registration URL : http://www.ClinicalTrials.gov . Unique identifier: NCT 01583218.

Published
2017

5. The safety and efficacy of full- versus reduced-dose betrixaban in the Acute Medically Ill VTE (Venous Thromboembolism) Prevention With Extended-Duration Betrixaban (APEX) trial

Author

Raymuno, S., Ramacciotti, E., Manenti, E., Freire, A., Fiss, E., Bizzacchi, J. Annichino, Lienart, F., Dive, A., Delforge, M., Blockmans, D., Soroka, N., Kamenova, Z., Kostadinova, M., Milanova, M., Pencheva, G., Runev, N., Stoeva, N., Stoyanov, M., Syulemzova, S., Todorov, G., Polonetsy, L., Pimanov, S., Mitkovskaya, N., Tokmakova, M., Dhar, A., Mikhailova, E., Koryk, V., Adzerikho, I., Schoenerr, H., Mathies, R., Douketis, J., Konig, J., Le Gal, G., Pearce, M., Provencher, S., Verreault, S., Alarcon, M. Arias, Lazcano, M. Opazo, Cardenas, S. Potthoff, Butkovic-Soldo, S., Car, S., Ciglenecki, N., Francetic, I., Jakopovic, M., Kalinic-Grgorinic, H., Knezevic, A., Marusic, S., Vagic, J. Sikic, Skerk, V., Cermak, O., Gibson, C. Michael, Halaby, Rim, Korjian, Serge, Daaboul, Yazan, Arbetter, Douglas F., Yee, Megan K., Chlumsky, J., Chochola, J., Cizek, V., Goldhaber, Samuel Z., Hull, Russel, Hernandez, Adrian F., Huber, K., Lu, Shiao-ping, Dunaj, M., Dusek, J., Francek, L., Havelka, J., Herold, M., Holaj, R., Nazliel, BİJEN, Bandman, Olga, Leeds, Janet M., Gold, Alex, Harrington, Robert A., Bello, F., Ferrari, A. E., Jure, H., Macin, S., Oliva, M., Parody, M., Horny, I., Hubac, J., Jajtner, P., Kolman, P., Poy, C., Baker, R., Lang, P., Mikulova, J., Podpera, I., Reiterer, P., Spacek, R., Vejvoda, J., Vyhnanek, M., Christensen, H., Lassen, M., Storgaard, M., Tuxen, C., Urhammer, S., Lember, M., Uuetoa, T., Airaksinen, J., Honkaniemi, J., Kaaja, R., Saarinen, J., Tatlisumak, T., Vikman, S., Agraou, B., Aquilanti, S., Belhassane, A., Brisot, D., De Geeter, G., Coughlin, P., Finfer, S., Debourdeau, P., Decoulx, E., El Kouri, D., Falvo, N., Grange, C., Rubinfeld, A., Lacroix, P., Messas, E., Mismetti, P., Montaclair, K., Paleiron, N., Payot, L., Zakai, N., Yousef, K., Wichman, T., Whitman, B., Welker, J., Welch, M., Warner, A., Updegrove, J., Tuck, M., Stoltz, S., Sokol, S., Sharma, S., Shammas, N., Saba, F., Rodriguez, W., Rastogi, P., Rajan, R., Quintana, O., Pullman, J., Pratt, R., Pineda, L., Pernod, G., Pearl, R., Parthiban, K., Ortel, T., Ohaju, V., Pottier, P., Proust, A., Quere, I., Roy, P-M., Schmidt, J., Simoneau, G., Datikashvili-David, I., Khabeishvili, G., Khintibidze, I., Nadar, V., Mittal, M., Milling, T., McLaren, G., Margolis, B., Mahal, S., Macchiavelli, A., Lopez, J., Lerner, R., Kung, M., Kouras, F., Kazimir, M., Kao, C-K., Kabler, H., Ioachimescu, O., Hazelrigg, M., Hamad, A., Haidar, A., Hahn, B., Goytia-Leos, D., Gaggin, H., Fulmer, J., Fraiz, J., Fermann, G., Farley, B., Doshi, A., Dhingra, R., Cornell, J., Concha, M., Clark, C., Chang, H., Carman, T., Bidair, M., Bercz, P., Bastani, A., Barney, J., Baker, S., Anderson, C., Amin, M., Almasri, E., Natarajan, I., McCollum, C., MacCallum, P., Davis, M., Body, R., Yagensky, A., Voronkov, L., Vishnivestsky, I., Vakaliuk, I., Ursol, G., Tseluyko, V., Svyshchenko, Y., Svyridova, I., Ryabichenko, T., Rudenko, L., Reshotko, D., Perepeliuk, M., Parkhomenko, O., Nikonov, V., Maslovaskyi, V., Malynovsky, Y., Legkonogov, O., Kyrychenko, I., Krakhmalova, O., Koshlia, V., Kopytsya, M., Karpenko, O., Gryb, V., Goncharova, Y., Goloborodko, B., Goloborodko, A., Godlevska, O., Burmak, I., Brozhyk, J., Batushkin, V., Abrahamovych, O., Tuncay, E., Topcuoglu, M., Tigen, K., Okumus, G., Kutluk, H., Kirma, C., Kilichesmez, K., Guneri, S., Akgul, O., Villalta, J., Vargas Nunez, J. A., Trujillo, J., Riera, A., Richart, C., Mellibovsky, L., Jimenez, D., Grandes, J., Gonzales-Porras, J. R., Gomez Cerezo, J., Ferrer, R., Diaz Santos, E., Cereto, F., Cepeda, J. M., Castro Guardiola, A., Bisbe, J., Barbagelata Lopez, C., Alvarez Sala, L. A., Van Dyk, C., Mitha, I., Engelbrecht, J., Breedt, J., Basson, M., Adler, D., Spisakova, M., Payer, J., Krastev, G., Kokles, M., Hrubon, A., Herman, O., Dvorak, M., Cervenakova, A., Bodikova, S., Miloradovic, V., Kovacevic-Kuzmanovic, A., Ilic, S., Celic, V., Apostolovic, S., Vishnevskiy, A., Vishneva, E., Solovyov, O., Simanenkov, V., Shvarts, Y., Shpagina, L., Shapovalova, Y., Sergeeva, E., Reshetko, O., Privalova, E., Popov, D., Nilk, R., Nikolaev, K., Mordovin, V., Maslova, N., Martynenko, V., Martynenko, T., Malygin, A., Kostenko, V., Kosmacheva, E., Kobalava, Z., Klein, G., Khachatryan, N., Ershova, O., Dovgalevskiy, Y., Chefranova, Z., Boldueva, S., Bogdanov, E., Belskaya, G., Barbarash, O., Averkov, O., Arkhipov, M., Apartsin, K., Andreev, D., Abashev, A., Vida-Simiti, L., Stanciulescu, G., Stamate, S., Kobulia, B., Megreladze, I., Pagava, Z., Paposhvili, K., Amann, B., Beyer-Westendorf, J., Blessing, E., Bott, M., Dengler, T., Dziewas, R., Genth-Zotz, S., Hamann, F., Horacek, T., Klimpe, S., Kroning, R., Lapp, H., Lawall, H., Licka, M., Rizos, T., Tiefenbacher, C., Weimar, C., Alkonyi, B., Falukozy, J., Futo, L., Katona, A., Kirschner, R., Kristof, P., Lakatos, F., Lupkovics, G., Merkely, B., Andras, C. Nagy, Nemeth, L., Papp, A., Soltesz, P., Sudar, Z., Szabo, G., Szegedi, N., Timar, G., Valco, J., Vertes, A., Efrati, S., Elias, M., Gafter, A., Hayek, T., Hussein, O., Lishner, M., Lugassy, G., Cerveri, I., D'Angelo, A., De Pellegrin, A., Imberti, D., Landolfi, R., Lembo, G., Lodigiani, C., Moia, M., Molteni, M., Mumoli, N., Novo, S., Orlandini, F., Parisi, R., Pizzini, A., Pomero, F., Salvi, A., Schenone, A., Visona, A., Martinova, V., Pontaga, N., Rozitis, V., Stukena, I., Alekniene, B., Basijokiene, V., Butkiene, Z., Griskeviciene, V., Naudziunas, A., Norvaisiene, R., Norviliene, R., Petrauskiene, R., Poskiene, R., Susinskiene, D., Valavicius, A., Castillo Leon, R., Pereyra, R. Cotrina, Karlo, L. Farjardo, Horna, M., Salas, M., Yanez, L. Toche, Fryze, W., Gaciong, Z., Gniot, J., Gorecka, D., Gruenpeter, P., Grzelakowski, P., Jastrzebski, D., Kucharski, L., Mirek-Bryniarska, E., Pulkowski, G., Sobkowicz, B., Sulik, P., Walasek, L., Waldemar, K., Wrzesinski, K., Balogh, Z. E., Bojinca, M., Marin, I., Musetescu, R., Podoleanu, C., Popescu, M., Kalpachki, R., Grigorov, M., Dimov, B., Rocha, A., Goloshchekin, B., Berrouschot, J., Laszlo, Z., Rees, C., Overcash, J., Prokop, D., and Cohen, Alexander T.

Subjects
Relative risk reduction, Male, Pyridines, Population, Hemorrhage, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pharmacokinetics, Randomized controlled trial, Double-Blind Method, law, Medicine, Humans, 030212 general & internal medicine, Dosing, Enoxaparin, education, Aged, Aged, 80 and over, Venous Thrombosis, education.field_of_study, business.industry, Absolute risk reduction, Anticoagulants, Venous Thromboembolism, Hospitalization, chemistry, Concomitant, Betrixaban, Anesthesia, Benzamides, Female, Cardiology and Cardiovascular Medicine, business, Pulmonary Embolism, Factor Xa Inhibitors
Abstract

The APEX trial assessed the safety and efficacy of extended-duration thromboprophylaxis using betrixaban versus standard dosing of enoxaparin among hospitalized, acutely ill medical patients. The 80-mg betrixaban dose was halved to 40 mg among subjects with severe renal insufficiency and those receiving a concomitant strong P-glycoprotein inhibitor.This analysis assessed the pharmacokinetics, efficacy, and safety of full- (80 mg) and reduced-dose (40 mg) betrixaban relative to enoxaparin in the APEX trial.The median concentration of betrixaban among subjects administered the 80-mg dose was higher than that of the 40-mg dose (19 ng/mL vs 11 ng/mL, P.001). In the primary analysis cohort 1 (d-dimer ≥2× upper limit of normal), the primary efficacy outcome (asymptomatic proximal deep vein thrombosis, symptomatic proximal or distal deep vein thrombosis, symptomatic nonfatal pulmonary embolism, or venous thromboembolism-related death) was significantly reduced among subjects treated with 80 mg of extended-duration betrixaban versus enoxaparin (6.27% [95/1516] vs 8.39% [130/1549], relative risk reduction=0.26 [0.04-0.42], P=.023), and similarly in the entire primary efficacy outcome population (4.87% [122/2506] vs 7.06% [181/2562], relative risk reduction=0.30 [0.13-0.44], P=.001). There was no difference in the primary outcome for subjects treated with 40 mg betrixaban vs enoxaparin across cohorts. In addition, there was no excess of major bleeding associated with either betrixaban dose compared with enoxaparin.The 80-mg betrixaban dose achieves higher plasma concentrations than the 40-mg dose and, in contrast to the 40-mg dose, is associated with improved efficacy across all cohorts relative to standard-dose enoxaparin without an excess risk of major bleeding in the management of medically ill subjects.

Published
2016

6. Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Author

Engelbrecht, J., Finfer, S., Van Dyk, C., Cohen, Alexander, Grandes, J., Cepeda, J. M., NAZLIEL, BİJEN, Cohen, Alexander T., Efrati, S., Zakai, N., Yousef, K., Wichman, T., Whitman, B., Welker, J., Welch, M., Warner, A., Updegrove, J., Tuck, M., Stoltz, S., Sokol, S., Sharma, S., Shammas, N., Saba, F., Rodriguez, W., Rees, C., Rastogi, P., Rajan, R., Quintana, O., Pullman, J., Pratt, R., Pineda, L., Pearl, R., Parthiban, K., Overcash, J., Ortel, T., Ohaju, V., Nadar, V., Mittal, M., Milling, T., McLaren, G., Margolis, B., Mahal, S., Macchiavelli, A., Lopez, J., Lerner, R., Kung, M., Kouras, F., Kazimir, M., Kao, C-K., Kabler, H., Ioachimescu, O., Hazelrigg, M., Hamad, A., Haidar, A., Hahn, B., Goytia-Leos, D., Gaggin, H., Fulmer, J., Fraiz, J., Fermann, G., Farley, B., Doshi, A., Dhingra, R., Cornell, J., Concha, M., Clark, C., Chang, H., Carman, T., Bidair, M., Bercz, P., Bastani, A., Barney, J., Baker, S., Anderson, C., Amin, M., Almasri, E., Natarajan, I., McCollum, C., MacCallum, P., Davis, M., Body, R., Yagensky, A., Voronkov, L., Vishnivestsky, I., Vakaliuk, I., Ursol, G., Tseluyko, V., Svyshchenko, Y., Svyridova, I., Ryabichenko, T., Rudenko, L., Alekniene, B., Reshotko, D., Perepeliuk, M., Parkhomenko, O., Nikonov, V., Maslovaskyi, V., Malynovsky, Y., Legkonogov, O., Kyrychenko, I., Krakhmalova, O., Koshlia, V., Kopytsya, M., Karpenko, O., Gryb, V., Goncharova, Y., Goloborodko, B., Goloborodko, A., Godlevska, O., Burmak, I., Brozhyk, J., Batushkin, V., Abrahamovych, O., Tuncay, E., Topcuoglu, M., Tigen, K., Okumus, G., Kutluk, H., Kirma, C., Kilichesmez, K., Guneri, S., Akgul, O., Villalta, J., Vargas Nunez, J. A., Trujillo, J., Riera, A., Richart, C., Mellibovsky, L., Jimenez, D., Gonzales-Porras, J. R., Gomez Cerezo, J., Ferrer, R., Diaz Santos, E., Cereto, F., Castro Guardiola, A., Bisbe, J., Barbagelata Lopez, C., Alvarez Sala, L. A., Mitha, I., Breedt, J., Basson, M., Adler, D., Spisakova, M., Prokop, D., Payer, J., Krastev, G., Kokles, M., Hrubon, A., Herman, O., Dvorak, M., Cervenakova, A., Bodikova, S., Miloradovic, V., Kovacevic-Kuzmanovic, A., Ilic, S., Celic, V., Apostolovic, S., Vishnevskiy, A., Vishneva, E., Solovyov, O., Simanenkov, V., Shvarts, Y., Shpagina, L., Shapovalova, Y., Sergeeva, E., Reshetko, O., Privalova, E., Popov, D., Nilk, R., Nikolaev, K., Mordovin, V., Maslova, N., Martynenko, V., Martynenko, T., Malygin, A., Kostenko, V., Kosmacheva, E., Kobalava, Z., Klein, G., Khachatryan, N., Goloshchekin, B., Ershova, O., Dovgalevskiy, Y., Chefranova, Z., Boldueva, S., Bogdanov, E., Belskaya, G., Barbarash, O., Averkov, O., Arkhipov, M., Apartsin, K., Andreev, D., Abashev, A., Vida-Simiti, L., Stanciulescu, G., Stamate, S., Harrington, Robert A., Goldhaber, Samuel Z., Hull, Russell D., Popescu, M., Wiens, Brian L., Gold, Alex, Hernandez, Adrian F., Gibson, C. Michael, Harrington, Robert, Hull, Russell, Goldhaber, Samuel, Hernandez, Adrian, Ceresetto, Jose Manuel, Colquhoun, David, Pilger, Ernst, Polonetsky, Leonid, Podoleanu, C., Musetescu, R., Marin, I., Bojinca, M., Motte, Serge, Saraiva, Jose Francisco, Balogh, Z. E., Wrzesinski, K., Waldemar, K., Walasek, L., Raev, Dimitar, Mincheva, Valentina, Kahn, Susan, Sulik, P., Canon, Claudia Olivares, Malojcic, Branko, Mayer, Otto, Husted, Steen, Marandi, Toomas, Lassila, Riitta, Mottier, Dominique, Shaburishvili, Tamaz, Bauersachs, Rupert, Zeymer, Uwe, Hajko, Erik, Sobkowicz, B., Zeltser, David, Ageno, Walter, Krievins, Dainis, Bagdonas, Alfredas, Osores, Juan Lema, Tomkowski, Witold, Mot, Stefan, Panchenko, Elizaveta, Tan, Ru San, Gaspar, Ludovit, Jacobson, Barry, Monreal, Manuel, Ongen, Gul, Parkhomenko, Alexander, Uprichard, James, Pulkowski, G., Mirek-Bryniarska, E., Kucharski, L., Jastrzebski, D., Yusen, Roger, Grzelakowski, P., Merli, Geno, Gruenpeter, P., Gorecka, D., Gniot, J., Gaciong, Z., Fryze, W., Peacock, Frank, Schellong, Sebastian, Januzzi, James, Piovella, Franco, Cochet, Madeleine, Michalak, Nathan, Stepanchak, Maria, Spielman, Kathryn, Neal, Brandon, Florea, Ana, Chi, Gerald, Szlosek, Donald, Jain, Purva, Popma, Christopher, Korjian, Serge, Daaboul, Yazan, Halaby, Rim, Yanez, L. Toche, Lemor, Alejandro, Zacarkim, Marcelo, Romero, Gonzalo, Hernandez Elenes, Jesus Rosario, Alvarado, Alonso, Susheela, Ammu, Leitao, Meghan, Salas, M., Bandman, Olga, Horna, M., Strumph, Peter, Vinh, Nancy, Visona, A., Kostadinova, M., Vance, Annemarie, Moia, M., Wiens, Brian, Orlandini, F., Parisi, R., Pontaga, N., Smoak, Carey, Storgaard, M., Molteni, M., Castelino, Rennie, Goodman, Shelly, Stukena, I., Leeds, Janet, al-Khalidi, Hussein, Milanova, M., Karlo, L. Farjardo, Leimberger, Jeffrey, Phillips, Thomas, Rizos, T., Pencheva, G., Pomero, F., Francis, Charles, Novo, S., Pereyra, R. Cotrina, Tiefenbacher, C., Buller, Harry, Roberts, Robin, Prins, Martin, Weimar, C., Tuxen, C., Urhammer, S., Lember, M., Runev, N., Uuetoa, T., Spyropoulos, Alex, Carrier, Marc, Alkonyi, B., Lopes, Renato D., Horacek, T., Airaksinen, J., Honkaniemi, J., Pottier, P., Falukozy, J., Kaaja, R., Stoeva, N., Saarinen, J., Stoyanov, M., Pizzini, A., Devor, Adam, Tatlisumak, T., Kolls, Bradley, Dedrick, Joseph, Todd, Jamie, Jones, William Schuyler, Vikman, S., Agraou, B., Futo, L., Castillo Leon, R., Eapen, Zubin, Katona, A., Proust, A., Quere, I., Kirschner, R., Syulemzova, S., Valavicius, A., Todorov, G., Tokmakova, M., Dhar, A., Klimpe, S., Ahmad, Tariq, Brenna, J. Matthew, Douketis, J., Le Gal, G., Pearce, M., Susinskiene, D., Brito, Flavio, Provencher, S., Rozitis, V., Roy, P-M., Kroning, R., Gulack, Brian, Schmidt, J., Meza, James, Parikh, Kishan, Cooper, Lauren, Poskiene, R., Aquilanti, S., Lapp, H., Kristof, P., Lakatos, F., Laszlo, Z., Belhassane, A., Petrauskiene, R., Pagidipati, Neha, Simoneau, G., Verreault, S., Guimaraes, Patricia, Brisot, D., Perkins, Lynn M., De Geeter, G., Debourdeau, P., Alarcon, M. Arias, Lupkovics, G., Norviliene, R., Wilson, Matthew, Merkely, B., Lazcano, M. Opazo, Collier, Jeannie, Andras, C. Nagy, Cardenas, S. Potthoff, Butkovic-Soldo, S., Norvaisiene, R., Decoulx, E., Hayden, Nikieia, El Kouri, D., Car, S., Nemeth, L., Leizorovicz, Alain, Ciglenecki, N., Naudziunas, A., Datikashvili-David, I., Francetic, I., Jakopovic, M., Becker, Francois, Jennings, Lisa, Khabeishvili, G., Bello, F., Ferrari, A. E., Jure, H., Macin, S., Griskeviciene, V., Kalinic-Grgorinic, H., Falvo, N., Khintibidze, I., Grange, C., Kobulia, B., Knezevic, A., Megreladze, I., Marusic, S., Papp, A., Pagava, Z., Lawall, H., Oliva, M., Paposhvili, K., Parody, M., Amann, B., Soltesz, P., Sudar, Z., Butkiene, Z., Szabo, G., Vagic, J. Sikic, Szegedi, N., Poy, C., Timar, G., Skerk, V., Cermak, O., Valco, J., Baker, R., Coughlin, P., Vertes, A., Rubinfeld, A., Elias, M., Berrouschot, J., Gafter, A., Hayek, T., Chlumsky, J., Lacroix, P., Messas, E., Chochola, J., Cizek, V., Basijokiene, V., Hussein, O., Dunaj, M., Dusek, J., Huber, K., Lishner, M., Lugassy, G., Cerveri, I., D'Angelo, A., De Pellegrin, A., Francek, L., Havelka, J., Konig, J., Beyer-Westendorf, J., Herold, M., Holaj, R., Imberti, D., Landolfi, R., Blessing, E., Mathies, R., Schoenerr, H., Adzerikho, I., Koryk, V., Licka, M., Martinova, V., Horny, I., Mikhailova, E., Mitkovskaya, N., Pimanov, S., Polonetsy, L., Soroka, N., Blockmans, D., Delforge, M., Dive, A., Lienart, F., Bizzacchi, J. Annichino, Fiss, E., Mismetti, P., Freire, A., Hubac, J., Jajtner, P., Manenti, E., Ramacciotti, E., Lembo, G., Raymuno, S., Rocha, A., Kolman, P., Lang, P., Bott, M., Dengler, T., Mikulova, J., Dimov, B., Podpera, I., Reiterer, P., Dziewas, R., Montaclair, K., Genth-Zotz, S., Hamann, F., Paleiron, N., Spacek, R., Payot, L., Vejvoda, J., Vyhnanek, M., Christensen, H., Salvi, A., Lodigiani, C., Pernod, G., Grigorov, M., Lassen, M., Mumoli, N., Kalpachki, R., Kamenova, Z., Schenone, A., Guy's and St Thomas' Hospital [London], Stanford Medicine, Stanford University, Brigham and Women's Hospital [Boston], Thrombosis Research Unit, University of Calgary, Portola Pharmaceuticals (Portola), PORTOLA PHARMACEUTICALS, Division of Cardiology, Duke University Medical Center, Duke Clinical Research Institute (DCRI - DURHAM), Duke University [Durham], Beth Israel Deaconess Medical Center [Boston, USA], Harvard Medical School [Boston] (HMS), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)

Subjects
Male, Pyridines, Medizin, 030204 cardiovascular system & hematology, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, Risk Factors, law, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Ultrasonography, Venous Thrombosis, Factors de risc en les malalties, Medicine (all), Acute Disease, Adult, Aged, Benzamides, Double-Blind Method, Drug Administration Schedule, Factor Xa Inhibitors, Female, Fibrin Fibrinogen Degradation Products, Hemorrhage, Hospitalization, Humans, Middle Aged, Pulmonary Embolism, Venous Thromboembolism, General Medicine, 3. Good health, Pulmonary embolism, Venous thrombosis, Cohort, medicine.medical_specialty, Patients, Risk factors in diseases, Placebo, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Thromboembolism, medicine, Pacients, Betrixaban, Thromboprophylaxis, Acutely Ill Medical Patients, Tromboembolisme, business.industry, Settore MED/09 - MEDICINA INTERNA, ta3121, Population cohort, medicine.disease, Surgery, chemistry, Once daily, business
Abstract

Background\ud Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown.\ud \ud Methods\ud Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding.\ud \ud Results\ud A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55).\ud \ud Conclusions\ud Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.)

Published
2016
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