Benefit of Warfarin Compared With Aspirin in Patients With Heart Failure in Sinus Rhythm

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. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938.

Clinical and Echocardiographic Factors Associated With New-Onset Atrial Fibrillation in Heart Failure – Subanalysis of the WARCEF Trial –

“…Also, HF patients in the USA number an estimated 5.7 million, and approximately 70% of them are believed to be in sinus rhythm. 33 Therefore, the present findings apply to a large patient population. Limitations of the study include the availability of echocardiographic LA data in only approximately 50% of patients; the analyses were adjusted, however, for variables that differed between patients with and without LAD information, which should have lessened the possibility of an effect of selection bias on the results.…”

“…These results may help in the risk stratification of HF patients for new-onset AF, and perhaps select a subgroup of patients in whom prolonged cardiac rhythm monitoring may be warranted to facilitate the detection of silent AF episodes. Considering the millions of patients with HF and sinus rhythm in the USA, 33 and worldwide, even a slight improvement in the ability to predict new AF might result in an important stroke risk reduction at a population level, allowing the use of appropriate anticoagulant therapy at the appropriate time. 35 of AF exist.…”

Role of echocardiography in patients with stroke

“…No significant difference was observed in the primary outcome (ischemic stroke, intracerebral hemorrhage, or death from any cause), although ischemic stroke was significantly lower in the warfarin group than in the aspirin group (0.72 versus 1.36 events per 100 patient-years; hazard ratio, 0.52; p = 0.005). In the subgroup analysis, those aged <60 years benefited from warfarin compared with aspirin on the combined outcome of ischemic stroke, intracerebral hemorrhage, or death (4.81 versus 6.76 events per 100 patient-years; hazard ratio, 0.63; p = 0.001), whereas older patients (age !60 years) did not [26]. Furthermore, well-controlled warfarin treatment (time in the therapeutic range !60%) was associated with better outcome than treatment with aspirin [27].…”

Bleeding Risk and Antithrombotic Strategy in Patients With Sinus Rhythm and Heart Failure With Reduced Ejection Fraction Treated With Warfarin or Aspirin

“…These results are broadly consistent with our previous subgroup analysis showing that younger patients (age <60 years) enrolled in the WARCEF trial had reduced risk of death, ischemic stroke, or intracranial hemorrhage with warfarin therapy compared to aspirin. 18 In our current analysis, WARCEF participants with an OBRI risk score of 0 or 1 included most patients younger than 60 years, but also many patients who are older. Taken together, this subgroup consists of nearly two thirds of all patients enrolled in the WARCEF trial and accounts for more than half of all ischemic stroke events observed during the follow-up period.…”