Quality of Anticoagulation Control in Preventing Adverse Events in Patients with Heart Failure in Sinus Rhythm: Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction Trial Substudy

Shunichi Homma, John L.P. Thompson, Min Qian, Siqin Ye, Marco R. Di Tullio, Gregory Y.H. Lip, Douglas L. Mann, Ralph L. Sacco, Bruce Levin, Patrick M. Pullicino, Ronald S. Freudenberger, John R. Teerlink, Susan Graham, J. P. Mohr, Arthur J. Labovitz, Richard Buchsbaum, Conrado J. Estol, Dirk J. Lok, Piotr Ponikowski, Stefan D. AnkerS. Ammon, B. Massie, C. Moy, P. Gilbert, L. Gutmann, J. Marler, V. Mejia, A. Gabriel, 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, M. Del Valle, A. Sanford, 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, G. J. del Zoppo, G. W. Albers, M. Eliasziw, J. A. Hinchey, K. C. Johnston, 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, 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, S. Palmeri, 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, P. Kosolcharoen, L. Williams, V. Sorrell, B. Coull, D. Bruck, E. Ofili, M. Frankel, P. Jackson, M. Nanna, J. Yasen, 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, 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, M. Modzelewski, 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, R. Yufe, B. Donelly, T. Huynh, R. Cote, B. 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, J. Minuk, C. Schanz, A. Penn, L. Atkins, A. Ducharme, H. Brown, S. Zieroth, A. Muñoz, A. van Bujisen-Nutters, M. Daniels, A. Coppes, M. van Zagten, N. Elzebroek, K. Hamroui, P. de Kort, J. Vuijsters, E. Ziekenhuis, N. Holwerda, W. Hermans, R. van der Loo, E. Wajon, G. Hageman, G. Buchem-Damming, R. de Graaf Gasthuis, E. Ronner, A. van Hessen, G. A. Verheul, G. Linssen, L. 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, 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. Vegh, 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. Santi, P. Romia, O. Montaña, D. Malchik, F. Sokn, P. Schygiel, R. Porcile, F. 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, J. Litvinova, P. Loviska

Research output: Contribution to journalArticle

Abstract

Background-The aim of this study is to examine the relationship between time in the therapeutic range (TTR) and clinical outcomes in heart failure patients in sinus rhythm treated with warfarin. Methods and Results-We used data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death), with death alone, ischemic stroke alone, major hemorrhage alone, and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin-treated patients, with TTR being treated as a time-dependent covariate. A total of 2217 patients were included in the analyses; among whom 1067 were randomized to warfarin and 1150 were randomized to aspirin. The median (interquartile range) follow-up duration was 3.6 (2.0-5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted P<0.001), death alone (adjusted P=0.001), and improved net clinical benefit (adjusted P<0.001). A similar trend was observed for the other 2 outcomes, but significance was not reached (adjusted P=0.082 for ischemic stroke and adjusted P=0.109 for major hemorrhage). Conclusions-In patients with heart failure in sinus rhythm, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938.

Original languageEnglish (US)
Pages (from-to)504-509
Number of pages6
JournalCirculation: Heart Failure
Volume8
Issue number3
DOIs
StatePublished - May 4 2015
Externally publishedYes

Fingerprint

Predictive Value of Tests
Drug Monitoring
Platelet Aggregation Inhibitors
Cerebral Hemorrhage
Warfarin
Chi-Square Distribution
Brain Ischemia
Left Ventricular Function
Proportional Hazards Models
Double-Blind Method
Quality Control
Stroke Volume
Anticoagulants
Aspirin
Multivariate Analysis
Heart Failure
Heart Rate
Stroke
Hemorrhage
Therapeutics

Keywords

  • anticoagulant
  • heart failure
  • hemorrhage
  • stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Quality of Anticoagulation Control in Preventing Adverse Events in Patients with Heart Failure in Sinus Rhythm : Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction Trial Substudy. / Homma, Shunichi; Thompson, John L.P.; Qian, Min; Ye, Siqin; Di Tullio, Marco R.; Lip, Gregory Y.H.; Mann, Douglas L.; Sacco, Ralph L.; Levin, Bruce; Pullicino, Patrick M.; Freudenberger, Ronald S.; Teerlink, John R.; Graham, Susan; Mohr, J. P.; Labovitz, Arthur J.; Buchsbaum, Richard; Estol, Conrado J.; Lok, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.; Ammon, S.; Massie, B.; Moy, C.; Gilbert, P.; Gutmann, L.; Marler, J.; Mejia, V.; Gabriel, A.; 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.; Del Valle, M.; Sanford, A.; 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.; del Zoppo, G. J.; Albers, G. W.; Eliasziw, M.; Hinchey, J. A.; Johnston, K. C.; 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.; 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.; Palmeri, S.; 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.; Kosolcharoen, P.; Williams, L.; Sorrell, V.; Coull, B.; Bruck, D.; Ofili, E.; Frankel, M.; Jackson, P.; Nanna, M.; Yasen, J.; 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.; 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.; Modzelewski, 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.; Yufe, R.; Donelly, B.; Huynh, T.; Cote, R.; 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.; Minuk, J.; Schanz, C.; Penn, A.; Atkins, L.; Ducharme, A.; Brown, H.; Zieroth, S.; Muñoz, A.; van Bujisen-Nutters, A.; Daniels, M.; Coppes, A.; van Zagten, M.; Elzebroek, N.; Hamroui, K.; de Kort, P.; Vuijsters, J.; Ziekenhuis, E.; Holwerda, N.; Hermans, W.; van der Loo, R.; Wajon, E.; Hageman, G.; Buchem-Damming, G.; de Graaf Gasthuis, R.; Ronner, E.; van Hessen, A.; Verheul, G. A.; Linssen, G.; 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, 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.; Vegh, 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.; Santi, R.; Romia, P.; Montaña, O.; Malchik, D.; Sokn, F.; Schygiel, P.; Porcile, R.; 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.; Litvinova, J.; Loviska, P.

In: Circulation: Heart Failure, Vol. 8, No. 3, 04.05.2015, p. 504-509.

Research output: Contribution to journalArticle

Homma, S, Thompson, JLP, Qian, M, Ye, S, Di Tullio, MR, Lip, GYH, Mann, DL, Sacco, RL, Levin, B, Pullicino, PM, Freudenberger, RS, Teerlink, JR, Graham, S, Mohr, JP, Labovitz, AJ, Buchsbaum, R, Estol, CJ, Lok, DJ, Ponikowski, P, Anker, SD, Ammon, S, Massie, B, Moy, C, Gilbert, P, Gutmann, L, Marler, J, Mejia, V, Gabriel, A, 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, Del Valle, M, Sanford, A, 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, del Zoppo, GJ, Albers, GW, Eliasziw, M, Hinchey, JA, Johnston, KC, Swain, JA, Slomiak, S, Cape, L, Barnett, HJ, Bruno, A, Easton, JD, Levine, S, Sahlas, D, Bleyer, F, Carson, P, Ellis, A, Miller, A, 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, Palmeri, S, 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, Kosolcharoen, P, Williams, L, Sorrell, V, Coull, B, Bruck, D, Ofili, E, Frankel, M, Jackson, P, Nanna, M, Yasen, J, 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, 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, Modzelewski, 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, Yufe, R, Donelly, B, Huynh, T, Cote, R, 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, Minuk, J, Schanz, C, Penn, A, Atkins, L, Ducharme, A, Brown, H, Zieroth, S, Muñoz, A, van Bujisen-Nutters, A, Daniels, M, Coppes, A, van Zagten, M, Elzebroek, N, Hamroui, K, de Kort, P, Vuijsters, J, Ziekenhuis, E, Holwerda, N, Hermans, W, van der Loo, R, Wajon, E, Hageman, G, Buchem-Damming, G, de Graaf Gasthuis, R, Ronner, E, van Hessen, A, Verheul, GA, Linssen, G, 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, 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, Vegh, 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, Santi, R, Romia, P, Montaña, O, Malchik, D, Sokn, F, Schygiel, P, Porcile, R, 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, Litvinova, J & Loviska, P 2015, 'Quality of Anticoagulation Control in Preventing Adverse Events in Patients with Heart Failure in Sinus Rhythm: Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction Trial Substudy', Circulation: Heart Failure, vol. 8, no. 3, pp. 504-509. https://doi.org/10.1161/CIRCHEARTFAILURE.114.001725
Homma, Shunichi ; Thompson, John L.P. ; Qian, Min ; Ye, Siqin ; Di Tullio, Marco R. ; Lip, Gregory Y.H. ; Mann, Douglas L. ; Sacco, Ralph L. ; Levin, Bruce ; Pullicino, Patrick M. ; Freudenberger, Ronald S. ; Teerlink, John R. ; Graham, Susan ; Mohr, J. P. ; Labovitz, Arthur J. ; Buchsbaum, Richard ; Estol, Conrado J. ; Lok, Dirk J. ; Ponikowski, Piotr ; Anker, Stefan D. ; Ammon, S. ; Massie, B. ; Moy, C. ; Gilbert, P. ; Gutmann, L. ; Marler, J. ; Mejia, V. ; Gabriel, A. ; 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. ; Del Valle, M. ; Sanford, A. ; 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. ; del Zoppo, G. J. ; Albers, G. W. ; Eliasziw, M. ; Hinchey, J. A. ; Johnston, K. C. ; 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. ; 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. ; Palmeri, S. ; 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. ; Kosolcharoen, P. ; Williams, L. ; Sorrell, V. ; Coull, B. ; Bruck, D. ; Ofili, E. ; Frankel, M. ; Jackson, P. ; Nanna, M. ; Yasen, J. ; 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. ; 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. ; Modzelewski, 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. ; Yufe, R. ; Donelly, B. ; Huynh, T. ; Cote, R. ; 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. ; Minuk, J. ; Schanz, C. ; Penn, A. ; Atkins, L. ; Ducharme, A. ; Brown, H. ; Zieroth, S. ; Muñoz, A. ; van Bujisen-Nutters, A. ; Daniels, M. ; Coppes, A. ; van Zagten, M. ; Elzebroek, N. ; Hamroui, K. ; de Kort, P. ; Vuijsters, J. ; Ziekenhuis, E. ; Holwerda, N. ; Hermans, W. ; van der Loo, R. ; Wajon, E. ; Hageman, G. ; Buchem-Damming, G. ; de Graaf Gasthuis, R. ; Ronner, E. ; van Hessen, A. ; Verheul, G. A. ; Linssen, G. ; 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, 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. ; Vegh, 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. ; Santi, R. ; Romia, P. ; Montaña, O. ; Malchik, D. ; Sokn, F. ; Schygiel, P. ; Porcile, R. ; 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. ; Litvinova, J. ; Loviska, P. / Quality of Anticoagulation Control in Preventing Adverse Events in Patients with Heart Failure in Sinus Rhythm : Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction Trial Substudy. In: Circulation: Heart Failure. 2015 ; Vol. 8, No. 3. pp. 504-509.
@article{446e1f2f370949a7afa1fd87bccb48d8,
title = "Quality of Anticoagulation Control in Preventing Adverse Events in Patients with Heart Failure in Sinus Rhythm: Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction Trial Substudy",
abstract = "Background-The aim of this study is to examine the relationship between time in the therapeutic range (TTR) and clinical outcomes in heart failure patients in sinus rhythm treated with warfarin. Methods and Results-We used data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death), with death alone, ischemic stroke alone, major hemorrhage alone, and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin-treated patients, with TTR being treated as a time-dependent covariate. A total of 2217 patients were included in the analyses; among whom 1067 were randomized to warfarin and 1150 were randomized to aspirin. The median (interquartile range) follow-up duration was 3.6 (2.0-5.0) years. Mean (±SD) age was 61±11.3 years, with 80{\%} being men. The mean (±SD) TTR was 57{\%} (±28.5{\%}). Increasing TTR was significantly associated with reduction in primary outcome (adjusted P<0.001), death alone (adjusted P=0.001), and improved net clinical benefit (adjusted P<0.001). A similar trend was observed for the other 2 outcomes, but significance was not reached (adjusted P=0.082 for ischemic stroke and adjusted P=0.109 for major hemorrhage). Conclusions-In patients with heart failure in sinus rhythm, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938.",
keywords = "anticoagulant, heart failure, hemorrhage, stroke",
author = "Shunichi Homma and Thompson, {John L.P.} and Min Qian and Siqin Ye and {Di Tullio}, {Marco R.} and Lip, {Gregory Y.H.} and Mann, {Douglas L.} and Sacco, {Ralph L.} and Bruce Levin and Pullicino, {Patrick M.} and Freudenberger, {Ronald S.} and Teerlink, {John R.} and Susan Graham and Mohr, {J. P.} and Labovitz, {Arthur J.} and Richard Buchsbaum and Estol, {Conrado J.} and Lok, {Dirk J.} and Piotr Ponikowski and Anker, {Stefan D.} and S. Ammon and B. Massie and C. Moy and P. Gilbert and L. Gutmann and J. Marler and V. Mejia and A. Gabriel 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 {Del Valle}, M. and A. Sanford 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 {del Zoppo}, {G. J.} and Albers, {G. W.} and M. Eliasziw and Hinchey, {J. A.} and Johnston, {K. C.} 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 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 S. Palmeri 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 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 J. Yasen 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 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 M. Modzelewski 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 R. Yufe and B. Donelly and T. Huynh and R. Cote and B. Jacques 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 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 {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 E. Ziekenhuis and N. Holwerda and W. Hermans and {van der Loo}, R. and E. Wajon and G. Hageman and G. Buchem-Damming and {de Graaf Gasthuis}, R. and E. Ronner and {van Hessen}, A. and Verheul, {G. A.} and G. Linssen and L. Pas 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 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. Vegh 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 R. Santi and P. Romia and O. Monta{\~n}a and D. Malchik and F. Sokn and P. Schygiel and R. Porcile and F. Tito 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 J. Litvinova and P. Loviska",
year = "2015",
month = "5",
day = "4",
doi = "10.1161/CIRCHEARTFAILURE.114.001725",
language = "English (US)",
volume = "8",
pages = "504--509",
journal = "Circulation: Heart Failure",
issn = "1941-3297",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Quality of Anticoagulation Control in Preventing Adverse Events in Patients with Heart Failure in Sinus Rhythm

T2 - Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction Trial Substudy

AU - Homma, Shunichi

AU - Thompson, John L.P.

AU - Qian, Min

AU - Ye, Siqin

AU - Di Tullio, Marco R.

AU - Lip, Gregory Y.H.

AU - Mann, Douglas L.

AU - Sacco, Ralph L.

AU - Levin, Bruce

AU - Pullicino, Patrick M.

AU - Freudenberger, Ronald S.

AU - Teerlink, John R.

AU - Graham, Susan

AU - Mohr, J. P.

AU - Labovitz, Arthur J.

AU - Buchsbaum, Richard

AU - Estol, Conrado J.

AU - Lok, Dirk J.

AU - Ponikowski, Piotr

AU - Anker, Stefan D.

AU - Ammon, S.

AU - Massie, B.

AU - Moy, C.

AU - Gilbert, P.

AU - Gutmann, L.

AU - Marler, J.

AU - Mejia, V.

AU - Gabriel, A.

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 - Del Valle, M.

AU - Sanford, A.

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 - del Zoppo, G. J.

AU - Albers, G. W.

AU - Eliasziw, M.

AU - Hinchey, J. A.

AU - Johnston, K. C.

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 - 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 - Palmeri, S.

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 - 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 - Yasen, J.

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 - 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 - Modzelewski, 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 - Yufe, R.

AU - Donelly, B.

AU - Huynh, T.

AU - Cote, R.

AU - 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 - Minuk, J.

AU - Schanz, C.

AU - Penn, A.

AU - Atkins, L.

AU - Ducharme, A.

AU - Brown, H.

AU - Zieroth, S.

AU - Muñoz, A.

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 - Ziekenhuis, E.

AU - Holwerda, N.

AU - Hermans, W.

AU - van der Loo, R.

AU - Wajon, E.

AU - Hageman, G.

AU - Buchem-Damming, G.

AU - de Graaf Gasthuis, R.

AU - Ronner, E.

AU - van Hessen, A.

AU - Verheul, G. A.

AU - Linssen, G.

AU - 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, 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 - Vegh, 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 - Santi, R.

AU - Romia, P.

AU - Montaña, O.

AU - Malchik, D.

AU - Sokn, F.

AU - Schygiel, P.

AU - Porcile, R.

AU - 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 - Litvinova, J.

AU - Loviska, P.

PY - 2015/5/4

Y1 - 2015/5/4

N2 - Background-The aim of this study is to examine the relationship between time in the therapeutic range (TTR) and clinical outcomes in heart failure patients in sinus rhythm treated with warfarin. Methods and Results-We used data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death), with death alone, ischemic stroke alone, major hemorrhage alone, and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin-treated patients, with TTR being treated as a time-dependent covariate. A total of 2217 patients were included in the analyses; among whom 1067 were randomized to warfarin and 1150 were randomized to aspirin. The median (interquartile range) follow-up duration was 3.6 (2.0-5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted P<0.001), death alone (adjusted P=0.001), and improved net clinical benefit (adjusted P<0.001). A similar trend was observed for the other 2 outcomes, but significance was not reached (adjusted P=0.082 for ischemic stroke and adjusted P=0.109 for major hemorrhage). Conclusions-In patients with heart failure in sinus rhythm, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938.

AB - Background-The aim of this study is to examine the relationship between time in the therapeutic range (TTR) and clinical outcomes in heart failure patients in sinus rhythm treated with warfarin. Methods and Results-We used data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death), with death alone, ischemic stroke alone, major hemorrhage alone, and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin-treated patients, with TTR being treated as a time-dependent covariate. A total of 2217 patients were included in the analyses; among whom 1067 were randomized to warfarin and 1150 were randomized to aspirin. The median (interquartile range) follow-up duration was 3.6 (2.0-5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted P<0.001), death alone (adjusted P=0.001), and improved net clinical benefit (adjusted P<0.001). A similar trend was observed for the other 2 outcomes, but significance was not reached (adjusted P=0.082 for ischemic stroke and adjusted P=0.109 for major hemorrhage). Conclusions-In patients with heart failure in sinus rhythm, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938.

KW - anticoagulant

KW - heart failure

KW - hemorrhage

KW - stroke

UR - http://www.scopus.com/inward/record.url?scp=84942937011&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84942937011&partnerID=8YFLogxK

U2 - 10.1161/CIRCHEARTFAILURE.114.001725

DO - 10.1161/CIRCHEARTFAILURE.114.001725

M3 - Article

C2 - 25850425

AN - SCOPUS:84942937011

VL - 8

SP - 504

EP - 509

JO - Circulation: Heart Failure

JF - Circulation: Heart Failure

SN - 1941-3297

IS - 3

ER -