Benefit of warfarin compared with aspirin in patients with heart failure in sinus rhythm: A subgroup analysis of WARCEF, a randomized controlled trial

Shunichi Homma, John L P Thompson, Alexandra R. Sanford, Douglas L. Mann, Ralph L Sacco, Bruce Levin, Patrick M. Pullicino, Ronald S. Freudenberger, John R. Teerlink, Susan Graham, J. P. Mohr, Barry M. Massie, Arthur J. Labovitz, Marco R. Di Tullio, André P. Gabriel, Gregory Y H Lip, Conrado J. Estol, Dirk J. Lok, Piotr Ponikowski, Stefan D. Anker

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background-The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial found no difference in the primary outcome between warfarin and aspirin in 2305 patients with reduced left ventricular ejection fraction in sinus rhythm. However, it is unknown whether any subgroups benefit from warfarin or aspirin. Methods and Results-We used a Cox model stepwise selection procedure to identify subgroups that may benefit from warfarin or aspirin on the WARCEF primary outcome. A secondary analysis added major hemorrhage to the outcome. The primary efficacy outcome was time to the first to occur of ischemic stroke, intracerebral hemorrhage, or death. Only age group was a significant treatment effect modifier (P for interaction, 0.003). Younger patients benefited from warfarin over aspirin on the primary outcome (4.81 versus 6.76 events per 100 patient-years: hazard ratio, 0.63; 95% confidence interval, 0.48-0.84; P=0.001). In older patients, therapies did not differ (9.91 versus 9.01 events per 100 patient-years: hazard ratio, 1.09; 95% confidence interval, 0.88-1.35; P=0.44). With major hemorrhage added, in younger patients the event rate remained lower for warfarin than aspirin (5.41 versus 7.25 per 100 patient-years: hazard ratio, 0.68; 95% confidence interval, 0.52-0.89; P=0.005), but in older patients it became significantly higher for warfarin (11.80 versus 9.35 per 100 patient-years: hazard ratio, 1.25; 95% confidence interval, 1.02-1.53; P=0.03). Conclusions-In patients <60 years, warfarin improved outcomes over aspirin with or without inclusion of major hemorrhage. In patients ≥60 years, there was no treatment difference, but the aspirin group had significantly better outcomes when major hemorrhage was included.

Original languageEnglish
Pages (from-to)988-997
Number of pages10
JournalCirculation: Heart Failure
Volume6
Issue number5
DOIs
StatePublished - Sep 1 2013

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Warfarin
Aspirin
Randomized Controlled Trials
Heart Failure
Confidence Intervals
Hemorrhage
Cerebral Hemorrhage
Proportional Hazards Models
Stroke Volume
Therapeutics
Age Groups
Stroke

Keywords

  • Aspirin
  • Heart failure
  • Sinus rhythm
  • Stroke
  • Warfarin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Benefit of warfarin compared with aspirin in patients with heart failure in sinus rhythm : A subgroup analysis of WARCEF, a randomized controlled trial. / Homma, Shunichi; Thompson, John L P; Sanford, Alexandra R.; Mann, Douglas L.; Sacco, Ralph L; Levin, Bruce; Pullicino, Patrick M.; Freudenberger, Ronald S.; Teerlink, John R.; Graham, Susan; Mohr, J. P.; Massie, Barry M.; Labovitz, Arthur J.; Di Tullio, Marco R.; Gabriel, André P.; Lip, Gregory Y H; Estol, Conrado J.; Lok, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.

In: Circulation: Heart Failure, Vol. 6, No. 5, 01.09.2013, p. 988-997.

Research output: Contribution to journalArticle

Homma, S, Thompson, JLP, Sanford, AR, Mann, DL, Sacco, RL, Levin, B, Pullicino, PM, Freudenberger, RS, Teerlink, JR, Graham, S, Mohr, JP, Massie, BM, Labovitz, AJ, Di Tullio, MR, Gabriel, AP, Lip, GYH, Estol, CJ, Lok, DJ, Ponikowski, P & Anker, SD 2013, 'Benefit of warfarin compared with aspirin in patients with heart failure in sinus rhythm: A subgroup analysis of WARCEF, a randomized controlled trial', Circulation: Heart Failure, vol. 6, no. 5, pp. 988-997. https://doi.org/10.1161/CIRCHEARTFAILURE.113.000372
Homma, Shunichi ; Thompson, John L P ; Sanford, Alexandra R. ; Mann, Douglas L. ; Sacco, Ralph L ; Levin, Bruce ; Pullicino, Patrick M. ; Freudenberger, Ronald S. ; Teerlink, John R. ; Graham, Susan ; Mohr, J. P. ; Massie, Barry M. ; Labovitz, Arthur J. ; Di Tullio, Marco R. ; Gabriel, André P. ; Lip, Gregory Y H ; Estol, Conrado J. ; Lok, Dirk J. ; Ponikowski, Piotr ; Anker, Stefan D. / Benefit of warfarin compared with aspirin in patients with heart failure in sinus rhythm : A subgroup analysis of WARCEF, a randomized controlled trial. In: Circulation: Heart Failure. 2013 ; Vol. 6, No. 5. pp. 988-997.
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T2 - A subgroup analysis of WARCEF, a randomized controlled trial

AU - Homma, Shunichi

AU - Thompson, John L P

AU - Sanford, Alexandra R.

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 - Massie, Barry M.

AU - Labovitz, Arthur J.

AU - Di Tullio, Marco R.

AU - Gabriel, André P.

AU - Lip, Gregory Y H

AU - Estol, Conrado J.

AU - Lok, Dirk J.

AU - Ponikowski, Piotr

AU - Anker, Stefan D.

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N2 - Background-The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial found no difference in the primary outcome between warfarin and aspirin in 2305 patients with reduced left ventricular ejection fraction in sinus rhythm. However, it is unknown whether any subgroups benefit from warfarin or aspirin. Methods and Results-We used a Cox model stepwise selection procedure to identify subgroups that may benefit from warfarin or aspirin on the WARCEF primary outcome. A secondary analysis added major hemorrhage to the outcome. The primary efficacy outcome was time to the first to occur of ischemic stroke, intracerebral hemorrhage, or death. Only age group was a significant treatment effect modifier (P for interaction, 0.003). Younger patients benefited from warfarin over aspirin on the primary outcome (4.81 versus 6.76 events per 100 patient-years: hazard ratio, 0.63; 95% confidence interval, 0.48-0.84; P=0.001). In older patients, therapies did not differ (9.91 versus 9.01 events per 100 patient-years: hazard ratio, 1.09; 95% confidence interval, 0.88-1.35; P=0.44). With major hemorrhage added, in younger patients the event rate remained lower for warfarin than aspirin (5.41 versus 7.25 per 100 patient-years: hazard ratio, 0.68; 95% confidence interval, 0.52-0.89; P=0.005), but in older patients it became significantly higher for warfarin (11.80 versus 9.35 per 100 patient-years: hazard ratio, 1.25; 95% confidence interval, 1.02-1.53; P=0.03). Conclusions-In patients <60 years, warfarin improved outcomes over aspirin with or without inclusion of major hemorrhage. In patients ≥60 years, there was no treatment difference, but the aspirin group had significantly better outcomes when major hemorrhage was included.

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KW - Aspirin

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