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.).
RCT Entities:
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.).
Authors: B F Uretsky; K Thygesen; P W Armstrong; J G Cleland; J D Horowitz; B M Massie; M Packer; P A Poole-Wilson; L Ryden Journal: Circulation Date: 2000-08-08 Impact factor: 29.690
Authors: E Loh; M S Sutton; C C Wun; J L Rouleau; G C Flaker; S S Gottlieb; G A Lamas; L A Moyé; S Z Goldhaber; M A Pfeffer Journal: N Engl J Med Date: 1997-01-23 Impact factor: 91.245
Authors: C Spaulding; B Charbonnier; A Cohen-Solal; Y Juillière; E P Kromer; K Benhamda; R Cador; S Weber Journal: Circulation Date: 1998-08-25 Impact factor: 29.690
Authors: Robert F van Es; Jan J C Jonker; Freek W A Verheugt; Jaap W Deckers; Diederick E Grobbee Journal: Lancet Date: 2002-07-13 Impact factor: 79.321
Authors: J G F Cleland; I Findlay; S Jafri; G Sutton; R Falk; C Bulpitt; C Prentice; I Ford; Adele Trainer; P A Poole-Wilson Journal: Am Heart J Date: 2004-07 Impact factor: 4.749
Authors: John R Teerlink; Min Qian; Natalie A Bello; Ronald S Freudenberger; Bruce Levin; Marco R Di Tullio; Susan Graham; Douglas L Mann; Ralph L Sacco; J P Mohr; Gregory Y H Lip; Arthur J Labovitz; Seitetz C Lee; Piotr Ponikowski; Dirk J Lok; Stefan D Anker; John L P Thompson; Shunichi Homma Journal: JACC Heart Fail Date: 2017-08 Impact factor: 12.035
Authors: Lorenzo Rossini; Pablo Martinez-Legazpi; Vi Vu; Leticia Fernández-Friera; Candelas Pérez Del Villar; Sara Rodríguez-López; Yolanda Benito; María-Guadalupe Borja; David Pastor-Escuredo; Raquel Yotti; María J Ledesma-Carbayo; Andrew M Kahn; Borja Ibáñez; Francisco Fernández-Avilés; Karen May-Newman; Javier Bermejo; Juan C Del Álamo Journal: J Biomech Date: 2015-11-30 Impact factor: 2.712
Authors: Tetz C Lee; Min Qian; Gregory Y H Lip; Marco R Di Tullio; Susan Graham; Douglas L Mann; Koki Nakanishi; John R Teerlink; Ronald S Freudenberger; Ralph L Sacco; J P Mohr; Arthur J Labovitz; Piotr Ponikowski; Dirk J Lok; Conrado Estol; Stefan D Anker; Patrick M Pullicino; Richard Buchsbaum; Bruce Levin; John L P Thompson; Shunichi Homma; Siqin Ye Journal: Am J Cardiol Date: 2018-06-04 Impact factor: 2.778
Authors: Renato D Lopes; Richard C Becker; L Kristin Newby; Eric D Peterson; Elaine M Hylek; Robert Giugliano; Christopher B Granger; Kenneth W Mahaffey; Antonio C Carvalho; Otavio Berwanger; Roberto R Giraldez; Gilson Soares Feitosa-Filho; Marcia M Barbosa; Maria da Consolacao V Moreira; Renato A K Kalil; Marildes Freitas; Joao Carlos de Campos Guerra; Marcio Vinicius Lins Barros; Thiago da Rocha Rodrigues; Antonio C Lopes; David A Garcia Journal: J Thromb Thrombolysis Date: 2013-07 Impact factor: 2.300