Warfarin and aspirin in patients with heart failure and sinus rhythm

Shunichi Homma, John L.P. Thompson, Patrick M. Pullicino, Bruce Levin, Ronald S. Freudenberger, John R. Teerlink, Susan E. Ammon, Susan Graham, Ralph L. Sacco, Douglas L. Mann, J. P. Mohr, Barry M. Massie, Arthur J. Labovitz, Stefan D. Anker, Dirk J. Lok, Piotr Ponikowski, Conrado J. Estol, Gregory Y.H. Lip, Marco R. Di Tullio, Alexandra R. Sanford & 515 others Vilma Mejia, Andre P. Gabriel, Mirna L. Del Valle, Richard Buchsbaum, C. Moy, P. Gilbert, L. Gutmann, J. Marler, S. Borden, E. Peña, C. Harris, R. Khadouri, D. Gohs, M. Brown, G. Berry, D. Disantis, M. Scullin, P. Smith, S. Kohsaka, W. Watson, L. Guillory, G. Levy, K. Tea, J. Grier, L. Swydan, B. O'Hare, R. Prodhan, R. Arbing, E. Flanagan, E. Duverger, A. Peljto, W. Lo, A. Tierney, A. Henriquez, J. Keen, G. J. del Zoppo, G. W. Albers, M. Eliasziw, J. A. Hinchey, K. C. Johnston, A. M. Lowe, Ileana L. Pina, J. A. Swain, S. Slomiak, L. Cape, H. J. Barnett, A. Bruno, J. D. Easton, S. Levine, D. Sahlas, F. Bleyer, P. Carson, A. Ellis, A. Miller, S. T. Palmeri, M. Bierig, R. Liu, C. Donato, R. Hart, C. McKay, L. Wilson, E. Frey, K. Hayward, P. Stein-Beal, L. Konczarek, M. Diek, M. Rohwedder, M. Bohdanowicz-Zazula, C. F. Peerenboom-Fey, M. Vissiennon, G. Rex, M. Varga, O. Kovtun, V. Orlyk, P. Arenberger, J. Jaros, A. Ruiz, M. Zimmermann, A. Ellenberg, A. Minagar, R. Kelley, J. McGee, P. Jinkins, S. Bezucha, V. Hart, M. Bonora, R. Sawyer, K. Ammerman, P. Ramappa, V. Berchou, E. Jones, E. Olgren, B. Hattler, C. Anderson, B. Watson, D. Wolf, J. Kosits, L. Casazza, D. Yip, J. Meschia, A. McPhail, K. Greenan, R. Rothbart, J. Love, T. Schrader, V. Garman, M. Stoddard, K. Remmel, R. Longaker, C. Gerula, M. Klapholz, J. Kirmani, R. Mattessich, C. Rodriguez, W. Graettinger, A. Baker, A. Valencia, P. Kosolcharoen, L. Williams, V. Sorrell, B. Coull, D. Bruck, E. Ofili, M. Frankel, P. Jackson, M. Nanna, S. Sparr, W. Almeida, R. Libman, B. Stephens, C. DeMers, T. Giles, L. Roffidal, D. Barratt, M. Liston, C. Lindsey, L. Giron, W. Felton, L. Joseph, M. Lee, J. Bisognano, C. Benesch, L. Caufield, E. Nishime, M. Moussavian, E. Polland, L. Fischer, K. Peterson, B. McGinnis, M. Tilem, G. Allam, J. Beebe, P. Chang, S. Sen, C. Schuler, L. Arcement, M. Charlet, E. Falgout, M. Malkowski, T. Dugan, J. Hobbs-Williams, A. Warner, K. Panizzon, J. Johnson, J. Dissin, D. Karia, N. Molakala, B. Dandapani, R. Vicari, E. Anthony, I. Katzan, R. Hobbs, A. Richmond, R. Hughes, W. Baker, M. Applegate, B. Drachman, S. Khella, S. Donovan, A. Slim, D. Pearce Moore, B. Darrow, A. Travis, A. Mercando, R. Pellegrino, N. Jarmukli, T. Ochalek, D. Janosik, J. Dizes, L. C. Pettigrew, D. Taylor, J. Hanna, S. Bailey, R. Berkowitz, S. Mathus, V. Virkud, S. Shaw, S. Nabhan, E. Wirkowski, B. George, E. Smith, S. Locke, C. Landau, D. Ferguson, H. V. Anderson, L. Westbrook, M. Apelian, S. Khoury, J. Leppo, T. Bator, U. Thadani, J. Turner, S. Goldman, S. Daugherty, A. Adler, T. Rennie, D. Chupka, R. Katz, L. Witkin, W. Burgin, C. Weber, J. Boehmer, P. Frey, M. Wilson, H. Tworek, G. Mallis, D. Mauceri, R. Schneider, W. Schneider, G. Ortiz, M. Lichtenberger, B. Hott, D. Patrick, S. Dunlap, S. J. Kim, S. Pezzella, D. Aubin, L. Nikolaidis, J. Wong, D. Leifer, M. Rossi, G. Torre, J. Arredondo, J. Lynch, A. Metcalf, J. Gonzalez, B. Donley, T. Cappola, K. Craig, B. Bozkurt, M. Bolos, T. Noonan, C. Alteri, L. Kowalczyk, A. Cwynar, D. Drazek, J. Biegus, R. Szelemej, M. Jurczok, R. Serafin, A. Jurczyk, M. Ogorek, D. Kopcik, B. Metzkier-Wyrwa, A. Szczepanska, M. Dluzniewski, W. Wicha, M. Kuch, K. Kuc, R. Piotrowski, O. Lesniak, M. Krauze-Wielicka, J. Herman, S. Nowakowska, T. Pasierski, B. Kozlowski, K. Wolkowska, A. Juszczak, J. Michalska, I. Jedlinski, P. Miekus, M. Konarzewski, P. Berkowski, N. Jacek, Z. Kalarus, A. Duszanska, J. Tarchalski, P. Czaja, Z. Gaciong, J. Gora, A. Kleinrok, G. Prokop-Lewicka, H. Haddad, R. Davies, L. Sitwell, J. Donaldson, T. To, R. Yufe, B. Donelly, T. Huynh, R. Cote, B. St Jacques, D. Borts, G. Tullio, A. M. Sindilar, T. Winder, E. Janzen, C. Walker, G. Moe, N. Bayer, A. Konig, M. Arnold, D. Spence, J. Smith, R. Bessoudo, P. Bailey, A. McNulty, S. Nawaz, C. Dewar, M. Rajda, M. MacFarlane, J. Minuk, C. Schanz, A. Penn, L. Atkins, A. Ducharme, H. Brown, S. Zieroth, A. Muñoz, J. B. ten Holter, C. Huls, P. Bruggink-Andre, A. van Bujisen-Nutters, M. Daniels, A. Coppes, M. van Zagten, N. Elzebroek, K. Hamroui, P. de Kort, J. Vuijsters, N. Holwerda, W. Hermans, R. van der Loo, E. Wajon, G. Hageman, G. v Buchem-Damming, E. Ronner, A. Wissenburg-van Lieshout, H. Niekus, M. W. van Hessen, G. A. Verheul, G. Linssen, L. te Pas, J. Plomp, P. A. de Milliano, R. Breedveld, M. J. Bos, M. Houra, D. Beran, R. Lebedova, J. Carda, E. Bednarova, J. Vosmerova, G. Marcinek, T. Drasnar, O. Najmanova, M. Dunaj, E. Pechackova, M. Kuchar, P. Jansky, J. Simon, H. Dvorakova, P. Gregor, M. Maruskova, L. Svoboda, Z. Lorenc, P. Kralicek, L. Pollak, Z. Krobot, M. Krobot, J. Spinar, M. Nemec, L. Spinarova, R. Kuba, F. Padour, I. Padourova, M. Padour, M. Michalova, L. Golan, M. Hajkova, J. Povolny, L. Krizova, D. Horak, P. Kucera, I. Malek, B. Krizova, J. Svoboda, R. Ferkl, L. Regos, L. Csuros, O. Lovasz, G. Kiss, S. Timar, N. Torok, A. Hajnalne, B. Palossy, A. Nagy, P. Fulop, G. Jakab, A. Ronaszeki, M. Bodi, M. Satori, I. Edes, I. Varga, A. Kovacs, L. Berente, E. Péterfai, R. Pauer, K. Toth, E. Nagy, B. Benczur, K. Karsay, T. Végh, R. Nagy, P. Karpati, Z. Davidovits, J. Borbola, J. Vanyi, B. Oze, A. Bujdoso, I. Kosa, L. Baliko, M. Natour, M. Morgil, E. Hartmann, H. Morgil, R. Winkler, S. Gass, S. Baumann, M. Jeserich, J. Rodl, M. Dzaiy, G. Turhan, K. Wolf, S. Genth-Zotz, T. Siebert, C. Jakobs, M. Kiorwantsi, B. Pieske, R. Wachter, M. Schoenauer, S. Voigt, H. Schunkert, A. Boguschewski, M. Resch, R. Wensel, V. Schumann, P. Heidrich, O. Girina, Y. Prokopovych, M. Lebedynska, I. Sorokina, O. Karpenko, N. Brodi, S. Klochkov, L. Voronkov, Y. Besaga, O. Novikova, K. Amosova, O. Yaremenko, K. Balaban, V. Kovalenko, N. Polenova, I. Sakharchuk, A. Ogorodnichuk, L. Rudenko, Y. Tutov, A. Parkhomenko, S. Kozhukhov, E. Yakimenko, S. Kolomiets, V. Yurlov, S. Tikhonova, A. Elizalde, B. Mangariello, C. Zaidman, F. Guerlloy, P. Gitelman, K. Crotto, S. Sassone, J. Aiub, F. Novoa, R. Lopez Santi, P. Romia, O. Montaña, D. Malchik, F. Sokn, P. Schygiel, R. Porcile, F. Soria Tito, J. Thierer, P. Avellana, C. Rapallo, M. Calderon, R. MacFadyen, R. Haynes, J. Partridge, M. Kokles, S. Mehešová, A. Zachar, M. Hranai, T. Varadyova, T. Göbö, J. Litvinova, P. Loviska

Research output: Contribution to journalArticle

300 Citations (Scopus)

Abstract

BACKGROUND: It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS: We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS: The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P = 0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P = 0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P = 0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P = 0.82). CONCLUSIONS: Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized. (Funded by the National Institute of Neurological Disorders and Stroke; WARCEF ClinicalTrials.gov number, NCT00041938.)

Original languageEnglish (US)
Pages (from-to)1859-1869
Number of pages11
JournalNew England Journal of Medicine
Volume366
Issue number20
DOIs
StatePublished - May 17 2012
Externally publishedYes

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Warfarin
Aspirin
Heart Failure
Stroke
Cerebral Hemorrhage
Stroke Volume
National Institute of Neurological Disorders and Stroke
Confidence Intervals
Hemorrhage
Therapeutics
International Normalized Ratio
Intracranial Hemorrhages
Cause of Death

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Homma, S., Thompson, J. L. P., Pullicino, P. M., Levin, B., Freudenberger, R. S., Teerlink, J. R., ... Loviska, P. (2012). Warfarin and aspirin in patients with heart failure and sinus rhythm. New England Journal of Medicine, 366(20), 1859-1869. https://doi.org/10.1056/NEJMoa1202299

Warfarin and aspirin in patients with heart failure and sinus rhythm. / Homma, Shunichi; Thompson, John L.P.; Pullicino, Patrick M.; Levin, Bruce; Freudenberger, Ronald S.; Teerlink, John R.; Ammon, Susan E.; Graham, Susan; Sacco, Ralph L.; Mann, Douglas L.; Mohr, J. P.; Massie, Barry M.; Labovitz, Arthur J.; Anker, Stefan D.; Lok, Dirk J.; Ponikowski, Piotr; Estol, Conrado J.; Lip, Gregory Y.H.; Di Tullio, Marco R.; Sanford, Alexandra R.; Mejia, Vilma; Gabriel, Andre P.; Del Valle, Mirna L.; Buchsbaum, Richard; Moy, C.; Gilbert, P.; Gutmann, L.; Marler, J.; Borden, S.; Peña, E.; Harris, C.; Khadouri, R.; Gohs, D.; Brown, M.; Berry, G.; Disantis, D.; Scullin, M.; Smith, P.; Kohsaka, S.; Watson, W.; Guillory, L.; Levy, G.; Tea, K.; Grier, J.; Swydan, L.; O'Hare, B.; Prodhan, R.; Arbing, R.; Flanagan, E.; Duverger, E.; Peljto, A.; Lo, W.; Tierney, A.; Henriquez, A.; Keen, J.; del Zoppo, G. J.; Albers, G. W.; Eliasziw, M.; Hinchey, J. A.; Johnston, K. C.; Lowe, A. M.; Pina, Ileana L.; Swain, J. A.; Slomiak, S.; Cape, L.; Barnett, H. J.; Bruno, A.; Easton, J. D.; Levine, S.; Sahlas, D.; Bleyer, F.; Carson, P.; Ellis, A.; Miller, A.; Palmeri, S. T.; Bierig, M.; Liu, R.; Donato, C.; Hart, R.; McKay, C.; Wilson, L.; Frey, E.; Hayward, K.; Stein-Beal, P.; Konczarek, L.; Diek, M.; Rohwedder, M.; Bohdanowicz-Zazula, M.; Peerenboom-Fey, C. F.; Vissiennon, M.; Rex, G.; Varga, M.; Kovtun, O.; Orlyk, V.; Arenberger, P.; Jaros, J.; Ruiz, A.; Zimmermann, M.; Ellenberg, A.; Minagar, A.; Kelley, R.; McGee, J.; Jinkins, P.; Bezucha, S.; Hart, V.; Bonora, M.; Sawyer, R.; Ammerman, K.; Ramappa, P.; Berchou, V.; Jones, E.; Olgren, E.; Hattler, B.; Anderson, C.; Watson, B.; Wolf, D.; Kosits, J.; Casazza, L.; Yip, D.; Meschia, J.; McPhail, A.; Greenan, K.; Rothbart, R.; Love, J.; Schrader, T.; Garman, V.; Stoddard, M.; Remmel, K.; Longaker, R.; Gerula, C.; Klapholz, M.; Kirmani, J.; Mattessich, R.; Rodriguez, C.; Graettinger, W.; Baker, A.; Valencia, A.; Kosolcharoen, P.; Williams, L.; Sorrell, V.; Coull, B.; Bruck, D.; Ofili, E.; Frankel, M.; Jackson, P.; Nanna, M.; Sparr, S.; Almeida, W.; Libman, R.; Stephens, B.; DeMers, C.; Giles, T.; Roffidal, L.; Barratt, D.; Liston, M.; Lindsey, C.; Giron, L.; Felton, W.; Joseph, L.; Lee, M.; Bisognano, J.; Benesch, C.; Caufield, L.; Nishime, E.; Moussavian, M.; Polland, E.; Fischer, L.; Peterson, K.; McGinnis, B.; Tilem, M.; Allam, G.; Beebe, J.; Chang, P.; Sen, S.; Schuler, C.; Arcement, L.; Charlet, M.; Falgout, E.; Malkowski, M.; Dugan, T.; Hobbs-Williams, J.; Warner, A.; Panizzon, K.; Johnson, J.; Dissin, J.; Karia, D.; Molakala, N.; Dandapani, B.; Vicari, R.; Anthony, E.; Katzan, I.; Hobbs, R.; Richmond, A.; Hughes, R.; Baker, W.; Applegate, M.; Drachman, B.; Khella, S.; Donovan, S.; Slim, A.; Pearce Moore, D.; Darrow, B.; Travis, A.; Mercando, A.; Pellegrino, R.; Jarmukli, N.; Ochalek, T.; Janosik, D.; Dizes, J.; Pettigrew, L. C.; Taylor, D.; Hanna, J.; Bailey, S.; Berkowitz, R.; Mathus, S.; Virkud, V.; Shaw, S.; Nabhan, S.; Wirkowski, E.; George, B.; Smith, E.; Locke, S.; Landau, C.; Ferguson, D.; Anderson, H. V.; Westbrook, L.; Apelian, M.; Khoury, S.; Leppo, J.; Bator, T.; Thadani, U.; Turner, J.; Goldman, S.; Daugherty, S.; Adler, A.; Rennie, T.; Chupka, D.; Katz, R.; Witkin, L.; Burgin, W.; Weber, C.; Boehmer, J.; Frey, P.; Wilson, M.; Tworek, H.; Mallis, G.; Mauceri, D.; Schneider, R.; Schneider, W.; Ortiz, G.; Lichtenberger, M.; Hott, B.; Patrick, D.; Dunlap, S.; Kim, S. J.; Pezzella, S.; Aubin, D.; Nikolaidis, L.; Wong, J.; Leifer, D.; Rossi, M.; Torre, G.; Arredondo, J.; Lynch, J.; Metcalf, A.; Gonzalez, J.; Donley, B.; Cappola, T.; Craig, K.; Bozkurt, B.; Bolos, M.; Noonan, T.; Alteri, C.; Kowalczyk, L.; Cwynar, A.; Drazek, D.; Biegus, J.; Szelemej, R.; Jurczok, M.; Serafin, R.; Jurczyk, A.; Ogorek, M.; Kopcik, D.; Metzkier-Wyrwa, B.; Szczepanska, A.; Dluzniewski, M.; Wicha, W.; Kuch, M.; Kuc, K.; Piotrowski, R.; Lesniak, O.; Krauze-Wielicka, M.; Herman, J.; Nowakowska, S.; Pasierski, T.; Kozlowski, B.; Wolkowska, K.; Juszczak, A.; Michalska, J.; Jedlinski, I.; Miekus, P.; Konarzewski, M.; Berkowski, P.; Jacek, N.; Kalarus, Z.; Duszanska, A.; Tarchalski, J.; Czaja, P.; Gaciong, Z.; Gora, J.; Kleinrok, A.; Prokop-Lewicka, G.; Haddad, H.; Davies, R.; Sitwell, L.; Donaldson, J.; To, T.; Yufe, R.; Donelly, B.; Huynh, T.; Cote, R.; St Jacques, B.; Borts, D.; Tullio, G.; Sindilar, A. M.; Winder, T.; Janzen, E.; Walker, C.; Moe, G.; Bayer, N.; Konig, A.; Arnold, M.; Spence, D.; Smith, J.; Bessoudo, R.; Bailey, P.; McNulty, A.; Nawaz, S.; Dewar, C.; Rajda, M.; MacFarlane, M.; Minuk, J.; Schanz, C.; Penn, A.; Atkins, L.; Ducharme, A.; Brown, H.; Zieroth, S.; Muñoz, A.; ten Holter, J. B.; Huls, C.; Bruggink-Andre, P.; van Bujisen-Nutters, A.; Daniels, M.; Coppes, A.; van Zagten, M.; Elzebroek, N.; Hamroui, K.; de Kort, P.; Vuijsters, J.; Holwerda, N.; Hermans, W.; van der Loo, R.; Wajon, E.; Hageman, G.; v Buchem-Damming, G.; Ronner, E.; Wissenburg-van Lieshout, A.; Niekus, H.; van Hessen, M. W.; Verheul, G. A.; Linssen, G.; te Pas, L.; Plomp, J.; de Milliano, P. A.; Breedveld, R.; Bos, M. J.; Houra, M.; Beran, D.; Lebedova, R.; Carda, J.; Bednarova, E.; Vosmerova, J.; Marcinek, G.; Drasnar, T.; Najmanova, O.; Dunaj, M.; Pechackova, E.; Kuchar, M.; Jansky, P.; Simon, J.; Dvorakova, H.; Gregor, P.; Maruskova, M.; Svoboda, L.; Lorenc, Z.; Kralicek, P.; Pollak, L.; Krobot, Z.; Krobot, M.; Spinar, J.; Nemec, M.; Spinarova, L.; Kuba, R.; Padour, F.; Padourova, I.; Padour, M.; Michalova, M.; Golan, L.; Hajkova, M.; Povolny, J.; Krizova, L.; Horak, D.; Kucera, P.; Malek, I.; Krizova, B.; Svoboda, J.; Ferkl, R.; Regos, L.; Csuros, L.; Lovasz, O.; Kiss, G.; Timar, S.; Torok, N.; Hajnalne, A.; Palossy, B.; Nagy, A.; Fulop, P.; Jakab, G.; Ronaszeki, A.; Bodi, M.; Satori, M.; Edes, I.; Varga, I.; Kovacs, A.; Berente, L.; Péterfai, E.; Pauer, R.; Toth, K.; Nagy, E.; Benczur, B.; Karsay, K.; Végh, T.; Nagy, R.; Karpati, P.; Davidovits, Z.; Borbola, J.; Vanyi, J.; Oze, B.; Bujdoso, A.; Kosa, I.; Baliko, L.; Natour, M.; Morgil, M.; Hartmann, E.; Morgil, H.; Winkler, R.; Gass, S.; Baumann, S.; Jeserich, M.; Rodl, J.; Dzaiy, M.; Turhan, G.; Wolf, K.; Genth-Zotz, S.; Siebert, T.; Jakobs, C.; Kiorwantsi, M.; Pieske, B.; Wachter, R.; Schoenauer, M.; Voigt, S.; Schunkert, H.; Boguschewski, A.; Resch, M.; Wensel, R.; Schumann, V.; Heidrich, P.; Girina, O.; Prokopovych, Y.; Lebedynska, M.; Sorokina, I.; Karpenko, O.; Brodi, N.; Klochkov, S.; Voronkov, L.; Besaga, Y.; Novikova, O.; Amosova, K.; Yaremenko, O.; Balaban, K.; Kovalenko, V.; Polenova, N.; Sakharchuk, I.; Ogorodnichuk, A.; Rudenko, L.; Tutov, Y.; Parkhomenko, A.; Kozhukhov, S.; Yakimenko, E.; Kolomiets, S.; Yurlov, V.; Tikhonova, S.; Elizalde, A.; Mangariello, B.; Zaidman, C.; Guerlloy, F.; Gitelman, P.; Crotto, K.; Sassone, S.; Aiub, J.; Novoa, F.; Lopez Santi, R.; Romia, P.; Montaña, O.; Malchik, D.; Sokn, F.; Schygiel, P.; Porcile, R.; Soria Tito, F.; Thierer, J.; Avellana, P.; Rapallo, C.; Calderon, M.; MacFadyen, R.; Haynes, R.; Partridge, J.; Kokles, M.; Mehešová, S.; Zachar, A.; Hranai, M.; Varadyova, T.; Göbö, T.; Litvinova, J.; Loviska, P.

In: New England Journal of Medicine, Vol. 366, No. 20, 17.05.2012, p. 1859-1869.

Research output: Contribution to journalArticle

Homma, S, Thompson, JLP, Pullicino, PM, Levin, B, Freudenberger, RS, Teerlink, JR, Ammon, SE, Graham, S, Sacco, RL, Mann, DL, Mohr, JP, Massie, BM, Labovitz, AJ, Anker, SD, Lok, DJ, Ponikowski, P, Estol, CJ, Lip, GYH, Di Tullio, MR, Sanford, AR, Mejia, V, Gabriel, AP, Del Valle, ML, Buchsbaum, R, Moy, C, Gilbert, P, Gutmann, L, Marler, J, Borden, S, Peña, E, Harris, C, Khadouri, R, Gohs, D, Brown, M, Berry, G, Disantis, D, Scullin, M, Smith, P, Kohsaka, S, Watson, W, Guillory, L, Levy, G, Tea, K, Grier, J, Swydan, L, O'Hare, B, Prodhan, R, Arbing, R, Flanagan, E, Duverger, E, Peljto, A, Lo, W, Tierney, A, Henriquez, A, Keen, J, del Zoppo, GJ, Albers, GW, Eliasziw, M, Hinchey, JA, Johnston, KC, Lowe, AM, Pina, IL, Swain, JA, Slomiak, S, Cape, L, Barnett, HJ, Bruno, A, Easton, JD, Levine, S, Sahlas, D, Bleyer, F, Carson, P, Ellis, A, Miller, A, Palmeri, ST, Bierig, M, Liu, R, Donato, C, Hart, R, McKay, C, Wilson, L, Frey, E, Hayward, K, Stein-Beal, P, Konczarek, L, Diek, M, Rohwedder, M, Bohdanowicz-Zazula, M, Peerenboom-Fey, CF, Vissiennon, M, Rex, G, Varga, M, Kovtun, O, Orlyk, V, Arenberger, P, Jaros, J, Ruiz, A, Zimmermann, M, Ellenberg, A, Minagar, A, Kelley, R, McGee, J, Jinkins, P, Bezucha, S, Hart, V, Bonora, M, Sawyer, R, Ammerman, K, Ramappa, P, Berchou, V, Jones, E, Olgren, E, Hattler, B, Anderson, C, Watson, B, Wolf, D, Kosits, J, Casazza, L, Yip, D, Meschia, J, McPhail, A, Greenan, K, Rothbart, R, Love, J, Schrader, T, Garman, V, Stoddard, M, Remmel, K, Longaker, R, Gerula, C, Klapholz, M, Kirmani, J, Mattessich, R, Rodriguez, C, Graettinger, W, Baker, A, Valencia, A, Kosolcharoen, P, Williams, L, Sorrell, V, Coull, B, Bruck, D, Ofili, E, Frankel, M, Jackson, P, Nanna, M, Sparr, S, Almeida, W, Libman, R, Stephens, B, DeMers, C, Giles, T, Roffidal, L, Barratt, D, Liston, M, Lindsey, C, Giron, L, Felton, W, Joseph, L, Lee, M, Bisognano, J, Benesch, C, Caufield, L, Nishime, E, Moussavian, M, Polland, E, Fischer, L, Peterson, K, McGinnis, B, Tilem, M, Allam, G, Beebe, J, Chang, P, Sen, S, Schuler, C, Arcement, L, Charlet, M, Falgout, E, Malkowski, M, Dugan, T, Hobbs-Williams, J, Warner, A, Panizzon, K, Johnson, J, Dissin, J, Karia, D, Molakala, N, Dandapani, B, Vicari, R, Anthony, E, Katzan, I, Hobbs, R, Richmond, A, Hughes, R, Baker, W, Applegate, M, Drachman, B, Khella, S, Donovan, S, Slim, A, Pearce Moore, D, Darrow, B, Travis, A, Mercando, A, Pellegrino, R, Jarmukli, N, Ochalek, T, Janosik, D, Dizes, J, Pettigrew, LC, Taylor, D, Hanna, J, Bailey, S, Berkowitz, R, Mathus, S, Virkud, V, Shaw, S, Nabhan, S, Wirkowski, E, George, B, Smith, E, Locke, S, Landau, C, Ferguson, D, Anderson, HV, Westbrook, L, Apelian, M, Khoury, S, Leppo, J, Bator, T, Thadani, U, Turner, J, Goldman, S, Daugherty, S, Adler, A, Rennie, T, Chupka, D, Katz, R, Witkin, L, Burgin, W, Weber, C, Boehmer, J, Frey, P, Wilson, M, Tworek, H, Mallis, G, Mauceri, D, Schneider, R, Schneider, W, Ortiz, G, Lichtenberger, M, Hott, B, Patrick, D, Dunlap, S, Kim, SJ, Pezzella, S, Aubin, D, Nikolaidis, L, Wong, J, Leifer, D, Rossi, M, Torre, G, Arredondo, J, Lynch, J, Metcalf, A, Gonzalez, J, Donley, B, Cappola, T, Craig, K, Bozkurt, B, Bolos, M, Noonan, T, Alteri, C, Kowalczyk, L, Cwynar, A, Drazek, D, Biegus, J, Szelemej, R, Jurczok, M, Serafin, R, Jurczyk, A, Ogorek, M, Kopcik, D, Metzkier-Wyrwa, B, Szczepanska, A, Dluzniewski, M, Wicha, W, Kuch, M, Kuc, K, Piotrowski, R, Lesniak, O, Krauze-Wielicka, M, Herman, J, Nowakowska, S, Pasierski, T, Kozlowski, B, Wolkowska, K, Juszczak, A, Michalska, J, Jedlinski, I, Miekus, P, Konarzewski, M, Berkowski, P, Jacek, N, Kalarus, Z, Duszanska, A, Tarchalski, J, Czaja, P, Gaciong, Z, Gora, J, Kleinrok, A, Prokop-Lewicka, G, Haddad, H, Davies, R, Sitwell, L, Donaldson, J, To, T, Yufe, R, Donelly, B, Huynh, T, Cote, R, St Jacques, B, Borts, D, Tullio, G, Sindilar, AM, Winder, T, Janzen, E, Walker, C, Moe, G, Bayer, N, Konig, A, Arnold, M, Spence, D, Smith, J, Bessoudo, R, Bailey, P, McNulty, A, Nawaz, S, Dewar, C, Rajda, M, MacFarlane, M, Minuk, J, Schanz, C, Penn, A, Atkins, L, Ducharme, A, Brown, H, Zieroth, S, Muñoz, A, ten Holter, JB, Huls, C, Bruggink-Andre, P, van Bujisen-Nutters, A, Daniels, M, Coppes, A, van Zagten, M, Elzebroek, N, Hamroui, K, de Kort, P, Vuijsters, J, Holwerda, N, Hermans, W, van der Loo, R, Wajon, E, Hageman, G, v Buchem-Damming, G, Ronner, E, Wissenburg-van Lieshout, A, Niekus, H, van Hessen, MW, Verheul, GA, Linssen, G, te Pas, L, Plomp, J, de Milliano, PA, Breedveld, R, Bos, MJ, Houra, M, Beran, D, Lebedova, R, Carda, J, Bednarova, E, Vosmerova, J, Marcinek, G, Drasnar, T, Najmanova, O, Dunaj, M, Pechackova, E, Kuchar, M, Jansky, P, Simon, J, Dvorakova, H, Gregor, P, Maruskova, M, Svoboda, L, Lorenc, Z, Kralicek, P, Pollak, L, Krobot, Z, Krobot, M, Spinar, J, Nemec, M, Spinarova, L, Kuba, R, Padour, F, Padourova, I, Padour, M, Michalova, M, Golan, L, Hajkova, M, Povolny, J, Krizova, L, Horak, D, Kucera, P, Malek, I, Krizova, B, Svoboda, J, Ferkl, R, Regos, L, Csuros, L, Lovasz, O, Kiss, G, Timar, S, Torok, N, Hajnalne, A, Palossy, B, Nagy, A, Fulop, P, Jakab, G, Ronaszeki, A, Bodi, M, Satori, M, Edes, I, Varga, I, Kovacs, A, Berente, L, Péterfai, E, Pauer, R, Toth, K, Nagy, E, Benczur, B, Karsay, K, Végh, T, Nagy, R, Karpati, P, Davidovits, Z, Borbola, J, Vanyi, J, Oze, B, Bujdoso, A, Kosa, I, Baliko, L, Natour, M, Morgil, M, Hartmann, E, Morgil, H, Winkler, R, Gass, S, Baumann, S, Jeserich, M, Rodl, J, Dzaiy, M, Turhan, G, Wolf, K, Genth-Zotz, S, Siebert, T, Jakobs, C, Kiorwantsi, M, Pieske, B, Wachter, R, Schoenauer, M, Voigt, S, Schunkert, H, Boguschewski, A, Resch, M, Wensel, R, Schumann, V, Heidrich, P, Girina, O, Prokopovych, Y, Lebedynska, M, Sorokina, I, Karpenko, O, Brodi, N, Klochkov, S, Voronkov, L, Besaga, Y, Novikova, O, Amosova, K, Yaremenko, O, Balaban, K, Kovalenko, V, Polenova, N, Sakharchuk, I, Ogorodnichuk, A, Rudenko, L, Tutov, Y, Parkhomenko, A, Kozhukhov, S, Yakimenko, E, Kolomiets, S, Yurlov, V, Tikhonova, S, Elizalde, A, Mangariello, B, Zaidman, C, Guerlloy, F, Gitelman, P, Crotto, K, Sassone, S, Aiub, J, Novoa, F, Lopez Santi, R, Romia, P, Montaña, O, Malchik, D, Sokn, F, Schygiel, P, Porcile, R, Soria Tito, F, Thierer, J, Avellana, P, Rapallo, C, Calderon, M, MacFadyen, R, Haynes, R, Partridge, J, Kokles, M, Mehešová, S, Zachar, A, Hranai, M, Varadyova, T, Göbö, T, Litvinova, J & Loviska, P 2012, 'Warfarin and aspirin in patients with heart failure and sinus rhythm', New England Journal of Medicine, vol. 366, no. 20, pp. 1859-1869. https://doi.org/10.1056/NEJMoa1202299
Homma S, Thompson JLP, Pullicino PM, Levin B, Freudenberger RS, Teerlink JR et al. Warfarin and aspirin in patients with heart failure and sinus rhythm. New England Journal of Medicine. 2012 May 17;366(20):1859-1869. https://doi.org/10.1056/NEJMoa1202299
Homma, Shunichi ; Thompson, John L.P. ; Pullicino, Patrick M. ; Levin, Bruce ; Freudenberger, Ronald S. ; Teerlink, John R. ; Ammon, Susan E. ; Graham, Susan ; Sacco, Ralph L. ; Mann, Douglas L. ; Mohr, J. P. ; Massie, Barry M. ; Labovitz, Arthur J. ; Anker, Stefan D. ; Lok, Dirk J. ; Ponikowski, Piotr ; Estol, Conrado J. ; Lip, Gregory Y.H. ; Di Tullio, Marco R. ; Sanford, Alexandra R. ; Mejia, Vilma ; Gabriel, Andre P. ; Del Valle, Mirna L. ; Buchsbaum, Richard ; Moy, C. ; Gilbert, P. ; Gutmann, L. ; Marler, J. ; Borden, S. ; Peña, E. ; Harris, C. ; Khadouri, R. ; Gohs, D. ; Brown, M. ; Berry, G. ; Disantis, D. ; Scullin, M. ; Smith, P. ; Kohsaka, S. ; Watson, W. ; Guillory, L. ; Levy, G. ; Tea, K. ; Grier, J. ; Swydan, L. ; O'Hare, B. ; Prodhan, R. ; Arbing, R. ; Flanagan, E. ; Duverger, E. ; Peljto, A. ; Lo, W. ; Tierney, A. ; Henriquez, A. ; Keen, J. ; del Zoppo, G. J. ; Albers, G. W. ; Eliasziw, M. ; Hinchey, J. A. ; Johnston, K. C. ; Lowe, A. M. ; Pina, Ileana L. ; Swain, J. A. ; Slomiak, S. ; Cape, L. ; Barnett, H. J. ; Bruno, A. ; Easton, J. D. ; Levine, S. ; Sahlas, D. ; Bleyer, F. ; Carson, P. ; Ellis, A. ; Miller, A. ; Palmeri, S. T. ; Bierig, M. ; Liu, R. ; Donato, C. ; Hart, R. ; McKay, C. ; Wilson, L. ; Frey, E. ; Hayward, K. ; Stein-Beal, P. ; Konczarek, L. ; Diek, M. ; Rohwedder, M. ; Bohdanowicz-Zazula, M. ; Peerenboom-Fey, C. F. ; Vissiennon, M. ; Rex, G. ; Varga, M. ; Kovtun, O. ; Orlyk, V. ; Arenberger, P. ; Jaros, J. ; Ruiz, A. ; Zimmermann, M. ; Ellenberg, A. ; Minagar, A. ; Kelley, R. ; McGee, J. ; Jinkins, P. ; Bezucha, S. ; Hart, V. ; Bonora, M. ; Sawyer, R. ; Ammerman, K. ; Ramappa, P. ; Berchou, V. ; Jones, E. ; Olgren, E. ; Hattler, B. ; Anderson, C. ; Watson, B. ; Wolf, D. ; Kosits, J. ; Casazza, L. ; Yip, D. ; Meschia, J. ; McPhail, A. ; Greenan, K. ; Rothbart, R. ; Love, J. ; Schrader, T. ; Garman, V. ; Stoddard, M. ; Remmel, K. ; Longaker, R. ; Gerula, C. ; Klapholz, M. ; Kirmani, J. ; Mattessich, R. ; Rodriguez, C. ; Graettinger, W. ; Baker, A. ; Valencia, A. ; Kosolcharoen, P. ; Williams, L. ; Sorrell, V. ; Coull, B. ; Bruck, D. ; Ofili, E. ; Frankel, M. ; Jackson, P. ; Nanna, M. ; Sparr, S. ; Almeida, W. ; Libman, R. ; Stephens, B. ; DeMers, C. ; Giles, T. ; Roffidal, L. ; Barratt, D. ; Liston, M. ; Lindsey, C. ; Giron, L. ; Felton, W. ; Joseph, L. ; Lee, M. ; Bisognano, J. ; Benesch, C. ; Caufield, L. ; Nishime, E. ; Moussavian, M. ; Polland, E. ; Fischer, L. ; Peterson, K. ; McGinnis, B. ; Tilem, M. ; Allam, G. ; Beebe, J. ; Chang, P. ; Sen, S. ; Schuler, C. ; Arcement, L. ; Charlet, M. ; Falgout, E. ; Malkowski, M. ; Dugan, T. ; Hobbs-Williams, J. ; Warner, A. ; Panizzon, K. ; Johnson, J. ; Dissin, J. ; Karia, D. ; Molakala, N. ; Dandapani, B. ; Vicari, R. ; Anthony, E. ; Katzan, I. ; Hobbs, R. ; Richmond, A. ; Hughes, R. ; Baker, W. ; Applegate, M. ; Drachman, B. ; Khella, S. ; Donovan, S. ; Slim, A. ; Pearce Moore, D. ; Darrow, B. ; Travis, A. ; Mercando, A. ; Pellegrino, R. ; Jarmukli, N. ; Ochalek, T. ; Janosik, D. ; Dizes, J. ; Pettigrew, L. C. ; Taylor, D. ; Hanna, J. ; Bailey, S. ; Berkowitz, R. ; Mathus, S. ; Virkud, V. ; Shaw, S. ; Nabhan, S. ; Wirkowski, E. ; George, B. ; Smith, E. ; Locke, S. ; Landau, C. ; Ferguson, D. ; Anderson, H. V. ; Westbrook, L. ; Apelian, M. ; Khoury, S. ; Leppo, J. ; Bator, T. ; Thadani, U. ; Turner, J. ; Goldman, S. ; Daugherty, S. ; Adler, A. ; Rennie, T. ; Chupka, D. ; Katz, R. ; Witkin, L. ; Burgin, W. ; Weber, C. ; Boehmer, J. ; Frey, P. ; Wilson, M. ; Tworek, H. ; Mallis, G. ; Mauceri, D. ; Schneider, R. ; Schneider, W. ; Ortiz, G. ; Lichtenberger, M. ; Hott, B. ; Patrick, D. ; Dunlap, S. ; Kim, S. J. ; Pezzella, S. ; Aubin, D. ; Nikolaidis, L. ; Wong, J. ; Leifer, D. ; Rossi, M. ; Torre, G. ; Arredondo, J. ; Lynch, J. ; Metcalf, A. ; Gonzalez, J. ; Donley, B. ; Cappola, T. ; Craig, K. ; Bozkurt, B. ; Bolos, M. ; Noonan, T. ; Alteri, C. ; Kowalczyk, L. ; Cwynar, A. ; Drazek, D. ; Biegus, J. ; Szelemej, R. ; Jurczok, M. ; Serafin, R. ; Jurczyk, A. ; Ogorek, M. ; Kopcik, D. ; Metzkier-Wyrwa, B. ; Szczepanska, A. ; Dluzniewski, M. ; Wicha, W. ; Kuch, M. ; Kuc, K. ; Piotrowski, R. ; Lesniak, O. ; Krauze-Wielicka, M. ; Herman, J. ; Nowakowska, S. ; Pasierski, T. ; Kozlowski, B. ; Wolkowska, K. ; Juszczak, A. ; Michalska, J. ; Jedlinski, I. ; Miekus, P. ; Konarzewski, M. ; Berkowski, P. ; Jacek, N. ; Kalarus, Z. ; Duszanska, A. ; Tarchalski, J. ; Czaja, P. ; Gaciong, Z. ; Gora, J. ; Kleinrok, A. ; Prokop-Lewicka, G. ; Haddad, H. ; Davies, R. ; Sitwell, L. ; Donaldson, J. ; To, T. ; Yufe, R. ; Donelly, B. ; Huynh, T. ; Cote, R. ; St Jacques, B. ; Borts, D. ; Tullio, G. ; Sindilar, A. M. ; Winder, T. ; Janzen, E. ; Walker, C. ; Moe, G. ; Bayer, N. ; Konig, A. ; Arnold, M. ; Spence, D. ; Smith, J. ; Bessoudo, R. ; Bailey, P. ; McNulty, A. ; Nawaz, S. ; Dewar, C. ; Rajda, M. ; MacFarlane, M. ; Minuk, J. ; Schanz, C. ; Penn, A. ; Atkins, L. ; Ducharme, A. ; Brown, H. ; Zieroth, S. ; Muñoz, A. ; ten Holter, J. B. ; Huls, C. ; Bruggink-Andre, P. ; van Bujisen-Nutters, A. ; Daniels, M. ; Coppes, A. ; van Zagten, M. ; Elzebroek, N. ; Hamroui, K. ; de Kort, P. ; Vuijsters, J. ; Holwerda, N. ; Hermans, W. ; van der Loo, R. ; Wajon, E. ; Hageman, G. ; v Buchem-Damming, G. ; Ronner, E. ; Wissenburg-van Lieshout, A. ; Niekus, H. ; van Hessen, M. W. ; Verheul, G. A. ; Linssen, G. ; te Pas, L. ; Plomp, J. ; de Milliano, P. A. ; Breedveld, R. ; Bos, M. J. ; Houra, M. ; Beran, D. ; Lebedova, R. ; Carda, J. ; Bednarova, E. ; Vosmerova, J. ; Marcinek, G. ; Drasnar, T. ; Najmanova, O. ; Dunaj, M. ; Pechackova, E. ; Kuchar, M. ; Jansky, P. ; Simon, J. ; Dvorakova, H. ; Gregor, P. ; Maruskova, M. ; Svoboda, L. ; Lorenc, Z. ; Kralicek, P. ; Pollak, L. ; Krobot, Z. ; Krobot, M. ; Spinar, J. ; Nemec, M. ; Spinarova, L. ; Kuba, R. ; Padour, F. ; Padourova, I. ; Padour, M. ; Michalova, M. ; Golan, L. ; Hajkova, M. ; Povolny, J. ; Krizova, L. ; Horak, D. ; Kucera, P. ; Malek, I. ; Krizova, B. ; Svoboda, J. ; Ferkl, R. ; Regos, L. ; Csuros, L. ; Lovasz, O. ; Kiss, G. ; Timar, S. ; Torok, N. ; Hajnalne, A. ; Palossy, B. ; Nagy, A. ; Fulop, P. ; Jakab, G. ; Ronaszeki, A. ; Bodi, M. ; Satori, M. ; Edes, I. ; Varga, I. ; Kovacs, A. ; Berente, L. ; Péterfai, E. ; Pauer, R. ; Toth, K. ; Nagy, E. ; Benczur, B. ; Karsay, K. ; Végh, T. ; Nagy, R. ; Karpati, P. ; Davidovits, Z. ; Borbola, J. ; Vanyi, J. ; Oze, B. ; Bujdoso, A. ; Kosa, I. ; Baliko, L. ; Natour, M. ; Morgil, M. ; Hartmann, E. ; Morgil, H. ; Winkler, R. ; Gass, S. ; Baumann, S. ; Jeserich, M. ; Rodl, J. ; Dzaiy, M. ; Turhan, G. ; Wolf, K. ; Genth-Zotz, S. ; Siebert, T. ; Jakobs, C. ; Kiorwantsi, M. ; Pieske, B. ; Wachter, R. ; Schoenauer, M. ; Voigt, S. ; Schunkert, H. ; Boguschewski, A. ; Resch, M. ; Wensel, R. ; Schumann, V. ; Heidrich, P. ; Girina, O. ; Prokopovych, Y. ; Lebedynska, M. ; Sorokina, I. ; Karpenko, O. ; Brodi, N. ; Klochkov, S. ; Voronkov, L. ; Besaga, Y. ; Novikova, O. ; Amosova, K. ; Yaremenko, O. ; Balaban, K. ; Kovalenko, V. ; Polenova, N. ; Sakharchuk, I. ; Ogorodnichuk, A. ; Rudenko, L. ; Tutov, Y. ; Parkhomenko, A. ; Kozhukhov, S. ; Yakimenko, E. ; Kolomiets, S. ; Yurlov, V. ; Tikhonova, S. ; Elizalde, A. ; Mangariello, B. ; Zaidman, C. ; Guerlloy, F. ; Gitelman, P. ; Crotto, K. ; Sassone, S. ; Aiub, J. ; Novoa, F. ; Lopez Santi, R. ; Romia, P. ; Montaña, O. ; Malchik, D. ; Sokn, F. ; Schygiel, P. ; Porcile, R. ; Soria Tito, F. ; Thierer, J. ; Avellana, P. ; Rapallo, C. ; Calderon, M. ; MacFadyen, R. ; Haynes, R. ; Partridge, J. ; Kokles, M. ; Mehešová, S. ; Zachar, A. ; Hranai, M. ; Varadyova, T. ; Göbö, T. ; Litvinova, J. ; Loviska, P. / Warfarin and aspirin in patients with heart failure and sinus rhythm. In: New England Journal of Medicine. 2012 ; Vol. 366, No. 20. pp. 1859-1869.
@article{cf235688d91a43148fddcb255684f6ac,
title = "Warfarin and aspirin in patients with heart failure and sinus rhythm",
abstract = "BACKGROUND: It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS: We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS: The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95{\%} confidence interval [CI], 0.79 to 1.10; P = 0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P = 0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95{\%} CI, 0.33 to 0.82; P = 0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P = 0.82). CONCLUSIONS: Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized. (Funded by the National Institute of Neurological Disorders and Stroke; WARCEF ClinicalTrials.gov number, NCT00041938.)",
author = "Shunichi Homma and Thompson, {John L.P.} and Pullicino, {Patrick M.} and Bruce Levin and Freudenberger, {Ronald S.} and Teerlink, {John R.} and Ammon, {Susan E.} and Susan Graham and Sacco, {Ralph L.} and Mann, {Douglas L.} and Mohr, {J. P.} and Massie, {Barry M.} and Labovitz, {Arthur J.} and Anker, {Stefan D.} and Lok, {Dirk J.} and Piotr Ponikowski and Estol, {Conrado J.} and Lip, {Gregory Y.H.} and {Di Tullio}, {Marco R.} and Sanford, {Alexandra R.} and Vilma Mejia and Gabriel, {Andre P.} and {Del Valle}, {Mirna L.} and Richard Buchsbaum and C. Moy and P. Gilbert and L. Gutmann and J. Marler and S. Borden and E. Pe{\~n}a and C. Harris and R. Khadouri and D. Gohs and M. Brown and G. Berry and D. Disantis and M. Scullin and P. Smith and S. Kohsaka and W. Watson and L. Guillory and G. Levy and K. Tea and J. Grier and L. Swydan and B. O'Hare and R. Prodhan and R. Arbing and E. Flanagan and E. Duverger and A. Peljto and W. Lo and A. Tierney and A. Henriquez and J. Keen and {del Zoppo}, {G. J.} and Albers, {G. W.} and M. Eliasziw and Hinchey, {J. A.} and Johnston, {K. C.} and Lowe, {A. M.} and Pina, {Ileana L.} and Swain, {J. A.} and S. Slomiak and L. Cape and Barnett, {H. J.} and A. Bruno and Easton, {J. D.} and S. Levine and D. Sahlas and F. Bleyer and P. Carson and A. Ellis and A. Miller and Palmeri, {S. T.} and M. Bierig and R. Liu and C. Donato and R. Hart and C. McKay and L. Wilson and E. Frey and K. Hayward and P. Stein-Beal and L. Konczarek and M. Diek and M. Rohwedder and M. Bohdanowicz-Zazula and Peerenboom-Fey, {C. F.} and M. Vissiennon and G. Rex and M. Varga and O. Kovtun and V. Orlyk and P. Arenberger and J. Jaros and A. Ruiz and M. Zimmermann and A. Ellenberg and A. Minagar and R. Kelley and J. McGee and P. Jinkins and S. Bezucha and V. Hart and M. Bonora and R. Sawyer and K. Ammerman and P. Ramappa and V. Berchou and E. Jones and E. Olgren and B. Hattler and C. Anderson and B. Watson and D. Wolf and J. Kosits and L. Casazza and D. Yip and J. Meschia and A. McPhail and K. Greenan and R. Rothbart and J. Love and T. Schrader and V. Garman and M. Stoddard and K. Remmel and R. Longaker and C. Gerula and M. Klapholz and J. Kirmani and R. Mattessich and C. Rodriguez and W. Graettinger and A. Baker and A. Valencia and P. Kosolcharoen and L. Williams and V. Sorrell and B. Coull and D. Bruck and E. Ofili and M. Frankel and P. Jackson and M. Nanna and S. Sparr and W. Almeida and R. Libman and B. Stephens and C. DeMers and T. Giles and L. Roffidal and D. Barratt and M. Liston and C. Lindsey and L. Giron and W. Felton and L. Joseph and M. Lee and J. Bisognano and C. Benesch and L. Caufield and E. Nishime and M. Moussavian and E. Polland and L. Fischer and K. Peterson and B. McGinnis and M. Tilem and G. Allam and J. Beebe and P. Chang and S. Sen and C. Schuler and L. Arcement and M. Charlet and E. Falgout and M. Malkowski and T. Dugan and J. Hobbs-Williams and A. Warner and K. Panizzon and J. Johnson and J. Dissin and D. Karia and N. Molakala and B. Dandapani and R. Vicari and E. Anthony and I. Katzan and R. Hobbs and A. Richmond and R. Hughes and W. Baker and M. Applegate and B. Drachman and S. Khella and S. Donovan and A. Slim and {Pearce Moore}, D. and B. Darrow and A. Travis and A. Mercando and R. Pellegrino and N. Jarmukli and T. Ochalek and D. Janosik and J. Dizes and Pettigrew, {L. C.} and D. Taylor and J. Hanna and S. Bailey and R. Berkowitz and S. Mathus and V. Virkud and S. Shaw and S. Nabhan and E. Wirkowski and B. George and E. Smith and S. Locke and C. Landau and D. Ferguson and Anderson, {H. V.} and L. Westbrook and M. Apelian and S. Khoury and J. Leppo and T. Bator and U. Thadani and J. Turner and S. Goldman and S. Daugherty and A. Adler and T. Rennie and D. Chupka and R. Katz and L. Witkin and W. Burgin and C. Weber and J. Boehmer and P. Frey and M. Wilson and H. Tworek and G. Mallis and D. Mauceri and R. Schneider and W. Schneider and G. Ortiz and M. Lichtenberger and B. Hott and D. Patrick and S. Dunlap and Kim, {S. J.} and S. Pezzella and D. Aubin and L. Nikolaidis and J. Wong and D. Leifer and M. Rossi and G. Torre and J. Arredondo and J. Lynch and A. Metcalf and J. Gonzalez and B. Donley and T. Cappola and K. Craig and B. Bozkurt and M. Bolos and T. Noonan and C. Alteri and L. Kowalczyk and A. Cwynar and D. Drazek and J. Biegus and R. Szelemej and M. Jurczok and R. Serafin and A. Jurczyk and M. Ogorek and D. Kopcik and B. Metzkier-Wyrwa and A. Szczepanska and M. Dluzniewski and W. Wicha and M. Kuch and K. Kuc and R. Piotrowski and O. Lesniak and M. Krauze-Wielicka and J. Herman and S. Nowakowska and T. Pasierski and B. Kozlowski and K. Wolkowska and A. Juszczak and J. Michalska and I. Jedlinski and P. Miekus and M. Konarzewski and P. Berkowski and N. Jacek and Z. Kalarus and A. Duszanska and J. Tarchalski and P. Czaja and Z. Gaciong and J. Gora and A. Kleinrok and G. Prokop-Lewicka and H. Haddad and R. Davies and L. Sitwell and J. Donaldson and T. To and R. Yufe and B. Donelly and T. Huynh and R. Cote and {St Jacques}, B. and D. Borts and G. Tullio and Sindilar, {A. M.} and T. Winder and E. Janzen and C. Walker and G. Moe and N. Bayer and A. Konig and M. Arnold and D. Spence and J. Smith and R. Bessoudo and P. Bailey and A. McNulty and S. Nawaz and C. Dewar and M. Rajda and M. MacFarlane and J. Minuk and C. Schanz and A. Penn and L. Atkins and A. Ducharme and H. Brown and S. Zieroth and A. Mu{\~n}oz and {ten Holter}, {J. B.} and C. Huls and P. Bruggink-Andre and {van Bujisen-Nutters}, A. and M. Daniels and A. Coppes and {van Zagten}, M. and N. Elzebroek and K. Hamroui and {de Kort}, P. and J. Vuijsters and N. Holwerda and W. Hermans and {van der Loo}, R. and E. Wajon and G. Hageman and {v Buchem-Damming}, G. and E. Ronner and {Wissenburg-van Lieshout}, A. and H. Niekus and {van Hessen}, {M. W.} and Verheul, {G. A.} and G. Linssen and {te Pas}, L. and J. Plomp and {de Milliano}, {P. A.} and R. Breedveld and Bos, {M. J.} and M. Houra and D. Beran and R. Lebedova and J. Carda and E. Bednarova and J. Vosmerova and G. Marcinek and T. Drasnar and O. Najmanova and M. Dunaj and E. Pechackova and M. Kuchar and P. Jansky and J. Simon and H. Dvorakova and P. Gregor and M. Maruskova and L. Svoboda and Z. Lorenc and P. Kralicek and L. Pollak and Z. Krobot and M. Krobot and J. Spinar and M. Nemec and L. Spinarova and R. Kuba and F. Padour and I. Padourova and M. Padour and M. Michalova and L. Golan and M. Hajkova and J. Povolny and L. Krizova and D. Horak and P. Kucera and I. Malek and B. Krizova and J. Svoboda and R. Ferkl and L. Regos and L. Csuros and O. Lovasz and G. Kiss and S. Timar and N. Torok and A. Hajnalne and B. Palossy and A. Nagy and P. Fulop and G. Jakab and A. Ronaszeki and M. Bodi and M. Satori and I. Edes and I. Varga and A. Kovacs and L. Berente and E. P{\'e}terfai and R. Pauer and K. Toth and E. Nagy and B. Benczur and K. Karsay and T. V{\'e}gh and R. Nagy and P. Karpati and Z. Davidovits and J. Borbola and J. Vanyi and B. Oze and A. Bujdoso and I. Kosa and L. Baliko and M. Natour and M. Morgil and E. Hartmann and H. Morgil and R. Winkler and S. Gass and S. Baumann and M. Jeserich and J. Rodl and M. Dzaiy and G. Turhan and K. Wolf and S. Genth-Zotz and T. Siebert and C. Jakobs and M. Kiorwantsi and B. Pieske and R. Wachter and M. Schoenauer and S. Voigt and H. Schunkert and A. Boguschewski and M. Resch and R. Wensel and V. Schumann and P. Heidrich and O. Girina and Y. Prokopovych and M. Lebedynska and I. Sorokina and O. Karpenko and N. Brodi and S. Klochkov and L. Voronkov and Y. Besaga and O. Novikova and K. Amosova and O. Yaremenko and K. Balaban and V. Kovalenko and N. Polenova and I. Sakharchuk and A. Ogorodnichuk and L. Rudenko and Y. Tutov and A. Parkhomenko and S. Kozhukhov and E. Yakimenko and S. Kolomiets and V. Yurlov and S. Tikhonova and A. Elizalde and B. Mangariello and C. Zaidman and F. Guerlloy and P. Gitelman and K. Crotto and S. Sassone and J. Aiub and F. Novoa and {Lopez Santi}, R. and P. Romia and O. Monta{\~n}a and D. Malchik and F. Sokn and P. Schygiel and R. Porcile and {Soria Tito}, F. and J. Thierer and P. Avellana and C. Rapallo and M. Calderon and R. MacFadyen and R. Haynes and J. Partridge and M. Kokles and S. Mehešov{\'a} and A. Zachar and M. Hranai and T. Varadyova and T. G{\"o}b{\"o} and J. Litvinova and P. Loviska",
year = "2012",
month = "5",
day = "17",
doi = "10.1056/NEJMoa1202299",
language = "English (US)",
volume = "366",
pages = "1859--1869",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "20",

}

TY - JOUR

T1 - Warfarin and aspirin in patients with heart failure and sinus rhythm

AU - Homma, Shunichi

AU - Thompson, John L.P.

AU - Pullicino, Patrick M.

AU - Levin, Bruce

AU - Freudenberger, Ronald S.

AU - Teerlink, John R.

AU - Ammon, Susan E.

AU - Graham, Susan

AU - Sacco, Ralph L.

AU - Mann, Douglas L.

AU - Mohr, J. P.

AU - Massie, Barry M.

AU - Labovitz, Arthur J.

AU - Anker, Stefan D.

AU - Lok, Dirk J.

AU - Ponikowski, Piotr

AU - Estol, Conrado J.

AU - Lip, Gregory Y.H.

AU - Di Tullio, Marco R.

AU - Sanford, Alexandra R.

AU - Mejia, Vilma

AU - Gabriel, Andre P.

AU - Del Valle, Mirna L.

AU - Buchsbaum, Richard

AU - Moy, C.

AU - Gilbert, P.

AU - Gutmann, L.

AU - Marler, J.

AU - Borden, S.

AU - Peña, E.

AU - Harris, C.

AU - Khadouri, R.

AU - Gohs, D.

AU - Brown, M.

AU - Berry, G.

AU - Disantis, D.

AU - Scullin, M.

AU - Smith, P.

AU - Kohsaka, S.

AU - Watson, W.

AU - Guillory, L.

AU - Levy, G.

AU - Tea, K.

AU - Grier, J.

AU - Swydan, L.

AU - O'Hare, B.

AU - Prodhan, R.

AU - Arbing, R.

AU - Flanagan, E.

AU - Duverger, E.

AU - Peljto, A.

AU - Lo, W.

AU - Tierney, A.

AU - Henriquez, A.

AU - Keen, J.

AU - del Zoppo, G. J.

AU - Albers, G. W.

AU - Eliasziw, M.

AU - Hinchey, J. A.

AU - Johnston, K. C.

AU - Lowe, A. M.

AU - Pina, Ileana L.

AU - Swain, J. A.

AU - Slomiak, S.

AU - Cape, L.

AU - Barnett, H. J.

AU - Bruno, A.

AU - Easton, J. D.

AU - Levine, S.

AU - Sahlas, D.

AU - Bleyer, F.

AU - Carson, P.

AU - Ellis, A.

AU - Miller, A.

AU - Palmeri, S. T.

AU - Bierig, M.

AU - Liu, R.

AU - Donato, C.

AU - Hart, R.

AU - McKay, C.

AU - Wilson, L.

AU - Frey, E.

AU - Hayward, K.

AU - Stein-Beal, P.

AU - Konczarek, L.

AU - Diek, M.

AU - Rohwedder, M.

AU - Bohdanowicz-Zazula, M.

AU - Peerenboom-Fey, C. F.

AU - Vissiennon, M.

AU - Rex, G.

AU - Varga, M.

AU - Kovtun, O.

AU - Orlyk, V.

AU - Arenberger, P.

AU - Jaros, J.

AU - Ruiz, A.

AU - Zimmermann, M.

AU - Ellenberg, A.

AU - Minagar, A.

AU - Kelley, R.

AU - McGee, J.

AU - Jinkins, P.

AU - Bezucha, S.

AU - Hart, V.

AU - Bonora, M.

AU - Sawyer, R.

AU - Ammerman, K.

AU - Ramappa, P.

AU - Berchou, V.

AU - Jones, E.

AU - Olgren, E.

AU - Hattler, B.

AU - Anderson, C.

AU - Watson, B.

AU - Wolf, D.

AU - Kosits, J.

AU - Casazza, L.

AU - Yip, D.

AU - Meschia, J.

AU - McPhail, A.

AU - Greenan, K.

AU - Rothbart, R.

AU - Love, J.

AU - Schrader, T.

AU - Garman, V.

AU - Stoddard, M.

AU - Remmel, K.

AU - Longaker, R.

AU - Gerula, C.

AU - Klapholz, M.

AU - Kirmani, J.

AU - Mattessich, R.

AU - Rodriguez, C.

AU - Graettinger, W.

AU - Baker, A.

AU - Valencia, A.

AU - Kosolcharoen, P.

AU - Williams, L.

AU - Sorrell, V.

AU - Coull, B.

AU - Bruck, D.

AU - Ofili, E.

AU - Frankel, M.

AU - Jackson, P.

AU - Nanna, M.

AU - Sparr, S.

AU - Almeida, W.

AU - Libman, R.

AU - Stephens, B.

AU - DeMers, C.

AU - Giles, T.

AU - Roffidal, L.

AU - Barratt, D.

AU - Liston, M.

AU - Lindsey, C.

AU - Giron, L.

AU - Felton, W.

AU - Joseph, L.

AU - Lee, M.

AU - Bisognano, J.

AU - Benesch, C.

AU - Caufield, L.

AU - Nishime, E.

AU - Moussavian, M.

AU - Polland, E.

AU - Fischer, L.

AU - Peterson, K.

AU - McGinnis, B.

AU - Tilem, M.

AU - Allam, G.

AU - Beebe, J.

AU - Chang, P.

AU - Sen, S.

AU - Schuler, C.

AU - Arcement, L.

AU - Charlet, M.

AU - Falgout, E.

AU - Malkowski, M.

AU - Dugan, T.

AU - Hobbs-Williams, J.

AU - Warner, A.

AU - Panizzon, K.

AU - Johnson, J.

AU - Dissin, J.

AU - Karia, D.

AU - Molakala, N.

AU - Dandapani, B.

AU - Vicari, R.

AU - Anthony, E.

AU - Katzan, I.

AU - Hobbs, R.

AU - Richmond, A.

AU - Hughes, R.

AU - Baker, W.

AU - Applegate, M.

AU - Drachman, B.

AU - Khella, S.

AU - Donovan, S.

AU - Slim, A.

AU - Pearce Moore, D.

AU - Darrow, B.

AU - Travis, A.

AU - Mercando, A.

AU - Pellegrino, R.

AU - Jarmukli, N.

AU - Ochalek, T.

AU - Janosik, D.

AU - Dizes, J.

AU - Pettigrew, L. C.

AU - Taylor, D.

AU - Hanna, J.

AU - Bailey, S.

AU - Berkowitz, R.

AU - Mathus, S.

AU - Virkud, V.

AU - Shaw, S.

AU - Nabhan, S.

AU - Wirkowski, E.

AU - George, B.

AU - Smith, E.

AU - Locke, S.

AU - Landau, C.

AU - Ferguson, D.

AU - Anderson, H. V.

AU - Westbrook, L.

AU - Apelian, M.

AU - Khoury, S.

AU - Leppo, J.

AU - Bator, T.

AU - Thadani, U.

AU - Turner, J.

AU - Goldman, S.

AU - Daugherty, S.

AU - Adler, A.

AU - Rennie, T.

AU - Chupka, D.

AU - Katz, R.

AU - Witkin, L.

AU - Burgin, W.

AU - Weber, C.

AU - Boehmer, J.

AU - Frey, P.

AU - Wilson, M.

AU - Tworek, H.

AU - Mallis, G.

AU - Mauceri, D.

AU - Schneider, R.

AU - Schneider, W.

AU - Ortiz, G.

AU - Lichtenberger, M.

AU - Hott, B.

AU - Patrick, D.

AU - Dunlap, S.

AU - Kim, S. J.

AU - Pezzella, S.

AU - Aubin, D.

AU - Nikolaidis, L.

AU - Wong, J.

AU - Leifer, D.

AU - Rossi, M.

AU - Torre, G.

AU - Arredondo, J.

AU - Lynch, J.

AU - Metcalf, A.

AU - Gonzalez, J.

AU - Donley, B.

AU - Cappola, T.

AU - Craig, K.

AU - Bozkurt, B.

AU - Bolos, M.

AU - Noonan, T.

AU - Alteri, C.

AU - Kowalczyk, L.

AU - Cwynar, A.

AU - Drazek, D.

AU - Biegus, J.

AU - Szelemej, R.

AU - Jurczok, M.

AU - Serafin, R.

AU - Jurczyk, A.

AU - Ogorek, M.

AU - Kopcik, D.

AU - Metzkier-Wyrwa, B.

AU - Szczepanska, A.

AU - Dluzniewski, M.

AU - Wicha, W.

AU - Kuch, M.

AU - Kuc, K.

AU - Piotrowski, R.

AU - Lesniak, O.

AU - Krauze-Wielicka, M.

AU - Herman, J.

AU - Nowakowska, S.

AU - Pasierski, T.

AU - Kozlowski, B.

AU - Wolkowska, K.

AU - Juszczak, A.

AU - Michalska, J.

AU - Jedlinski, I.

AU - Miekus, P.

AU - Konarzewski, M.

AU - Berkowski, P.

AU - Jacek, N.

AU - Kalarus, Z.

AU - Duszanska, A.

AU - Tarchalski, J.

AU - Czaja, P.

AU - Gaciong, Z.

AU - Gora, J.

AU - Kleinrok, A.

AU - Prokop-Lewicka, G.

AU - Haddad, H.

AU - Davies, R.

AU - Sitwell, L.

AU - Donaldson, J.

AU - To, T.

AU - Yufe, R.

AU - Donelly, B.

AU - Huynh, T.

AU - Cote, R.

AU - St Jacques, B.

AU - Borts, D.

AU - Tullio, G.

AU - Sindilar, A. M.

AU - Winder, T.

AU - Janzen, E.

AU - Walker, C.

AU - Moe, G.

AU - Bayer, N.

AU - Konig, A.

AU - Arnold, M.

AU - Spence, D.

AU - Smith, J.

AU - Bessoudo, R.

AU - Bailey, P.

AU - McNulty, A.

AU - Nawaz, S.

AU - Dewar, C.

AU - Rajda, M.

AU - MacFarlane, M.

AU - Minuk, J.

AU - Schanz, C.

AU - Penn, A.

AU - Atkins, L.

AU - Ducharme, A.

AU - Brown, H.

AU - Zieroth, S.

AU - Muñoz, A.

AU - ten Holter, J. B.

AU - Huls, C.

AU - Bruggink-Andre, P.

AU - van Bujisen-Nutters, A.

AU - Daniels, M.

AU - Coppes, A.

AU - van Zagten, M.

AU - Elzebroek, N.

AU - Hamroui, K.

AU - de Kort, P.

AU - Vuijsters, J.

AU - Holwerda, N.

AU - Hermans, W.

AU - van der Loo, R.

AU - Wajon, E.

AU - Hageman, G.

AU - v Buchem-Damming, G.

AU - Ronner, E.

AU - Wissenburg-van Lieshout, A.

AU - Niekus, H.

AU - van Hessen, M. W.

AU - Verheul, G. A.

AU - Linssen, G.

AU - te Pas, L.

AU - Plomp, J.

AU - de Milliano, P. A.

AU - Breedveld, R.

AU - Bos, M. J.

AU - Houra, M.

AU - Beran, D.

AU - Lebedova, R.

AU - Carda, J.

AU - Bednarova, E.

AU - Vosmerova, J.

AU - Marcinek, G.

AU - Drasnar, T.

AU - Najmanova, O.

AU - Dunaj, M.

AU - Pechackova, E.

AU - Kuchar, M.

AU - Jansky, P.

AU - Simon, J.

AU - Dvorakova, H.

AU - Gregor, P.

AU - Maruskova, M.

AU - Svoboda, L.

AU - Lorenc, Z.

AU - Kralicek, P.

AU - Pollak, L.

AU - Krobot, Z.

AU - Krobot, M.

AU - Spinar, J.

AU - Nemec, M.

AU - Spinarova, L.

AU - Kuba, R.

AU - Padour, F.

AU - Padourova, I.

AU - Padour, M.

AU - Michalova, M.

AU - Golan, L.

AU - Hajkova, M.

AU - Povolny, J.

AU - Krizova, L.

AU - Horak, D.

AU - Kucera, P.

AU - Malek, I.

AU - Krizova, B.

AU - Svoboda, J.

AU - Ferkl, R.

AU - Regos, L.

AU - Csuros, L.

AU - Lovasz, O.

AU - Kiss, G.

AU - Timar, S.

AU - Torok, N.

AU - Hajnalne, A.

AU - Palossy, B.

AU - Nagy, A.

AU - Fulop, P.

AU - Jakab, G.

AU - Ronaszeki, A.

AU - Bodi, M.

AU - Satori, M.

AU - Edes, I.

AU - Varga, I.

AU - Kovacs, A.

AU - Berente, L.

AU - Péterfai, E.

AU - Pauer, R.

AU - Toth, K.

AU - Nagy, E.

AU - Benczur, B.

AU - Karsay, K.

AU - Végh, T.

AU - Nagy, R.

AU - Karpati, P.

AU - Davidovits, Z.

AU - Borbola, J.

AU - Vanyi, J.

AU - Oze, B.

AU - Bujdoso, A.

AU - Kosa, I.

AU - Baliko, L.

AU - Natour, M.

AU - Morgil, M.

AU - Hartmann, E.

AU - Morgil, H.

AU - Winkler, R.

AU - Gass, S.

AU - Baumann, S.

AU - Jeserich, M.

AU - Rodl, J.

AU - Dzaiy, M.

AU - Turhan, G.

AU - Wolf, K.

AU - Genth-Zotz, S.

AU - Siebert, T.

AU - Jakobs, C.

AU - Kiorwantsi, M.

AU - Pieske, B.

AU - Wachter, R.

AU - Schoenauer, M.

AU - Voigt, S.

AU - Schunkert, H.

AU - Boguschewski, A.

AU - Resch, M.

AU - Wensel, R.

AU - Schumann, V.

AU - Heidrich, P.

AU - Girina, O.

AU - Prokopovych, Y.

AU - Lebedynska, M.

AU - Sorokina, I.

AU - Karpenko, O.

AU - Brodi, N.

AU - Klochkov, S.

AU - Voronkov, L.

AU - Besaga, Y.

AU - Novikova, O.

AU - Amosova, K.

AU - Yaremenko, O.

AU - Balaban, K.

AU - Kovalenko, V.

AU - Polenova, N.

AU - Sakharchuk, I.

AU - Ogorodnichuk, A.

AU - Rudenko, L.

AU - Tutov, Y.

AU - Parkhomenko, A.

AU - Kozhukhov, S.

AU - Yakimenko, E.

AU - Kolomiets, S.

AU - Yurlov, V.

AU - Tikhonova, S.

AU - Elizalde, A.

AU - Mangariello, B.

AU - Zaidman, C.

AU - Guerlloy, F.

AU - Gitelman, P.

AU - Crotto, K.

AU - Sassone, S.

AU - Aiub, J.

AU - Novoa, F.

AU - Lopez Santi, R.

AU - Romia, P.

AU - Montaña, O.

AU - Malchik, D.

AU - Sokn, F.

AU - Schygiel, P.

AU - Porcile, R.

AU - Soria Tito, F.

AU - Thierer, J.

AU - Avellana, P.

AU - Rapallo, C.

AU - Calderon, M.

AU - MacFadyen, R.

AU - Haynes, R.

AU - Partridge, J.

AU - Kokles, M.

AU - Mehešová, S.

AU - Zachar, A.

AU - Hranai, M.

AU - Varadyova, T.

AU - Göbö, T.

AU - Litvinova, J.

AU - Loviska, P.

PY - 2012/5/17

Y1 - 2012/5/17

N2 - BACKGROUND: It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS: We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS: The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P = 0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P = 0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P = 0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P = 0.82). CONCLUSIONS: Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized. (Funded by the National Institute of Neurological Disorders and Stroke; WARCEF ClinicalTrials.gov number, NCT00041938.)

AB - BACKGROUND: It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS: We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS: The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P = 0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P = 0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P = 0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P = 0.82). CONCLUSIONS: Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized. (Funded by the National Institute of Neurological Disorders and Stroke; WARCEF ClinicalTrials.gov number, NCT00041938.)

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U2 - 10.1056/NEJMoa1202299

DO - 10.1056/NEJMoa1202299

M3 - Article

VL - 366

SP - 1859

EP - 1869

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 20

ER -