Bayer Pharma AG

Essence of this Article

Limited data are available regarding anticoagulation therapy in patients with heart failure, and to date there have been no large studies that have evaluated antithrombotic prophylaxis specifically in patients with heart failure. Results from the WARCEF study showed that warfarin reduced the rate of ischaemic stroke relative to acetylsalicylic acid (ASA; aspirin). However, this benefit was offset by a higher risk of bleeding. Given these findings, the authors suggested that the choice between warfarin and ASA should be individualized based on each patient’s specific circumstances. Anticoagulant therapy for patients with coronary artery disease and heart failure is under investigation.

Anticoagulation of patients with heart failure

Limited data are available regarding anticoagulation therapy in patients with heart failure. Most venous thromboembolism (VTE) prevention studies that have been conducted in patients with heart failure are retrospective, include patients with other, concurrent conditions or are restricted to hospitalized patients.323, 325 Although several large clinical trials have been conducted exploring pharmacological prophylaxis in medically ill hospitalized patients, to date there have been no large studies that have evaluated antithrombotic prophylaxis specifically in patients with heart failure.

Two relatively small trials, WATCH (Warfarin and Antiplatelet Therapy in Chronic Heart failure) and WASH (Warfarin/Aspirin Study in Heart failure), have been conducted to compare oral anticoagulation with vitamin K antagonists with placebo, ASA or clopidogrel for the reduction of stroke in patients with heart failure.326, 327 Although results from both trials indicated that warfarin was more effective than ASA in reducing the incidence of stroke in this patient population, neither trial was sufficiently powered to definitively support the use of warfarin in patients with heart failure.

Results from the WARCEF (Warfarin versus Aspirin in ReduCed Ejection Fraction) study have provided greater clarity.328, 329 This study, which was designed to determine whether warfarin or ASA is more effective at preventing death and stroke in patients with poor heart function, included 2305 patients with a left ventricular ejection fraction ≤35% and sinus rhythm.329 Patients were randomized in a double-blind trial design to either warfarin treatment with a target international normalized ratio of 2.0–3.5 or ASA given at a dose of 325 mg daily.

The results from this trial show that for treatment with warfarin versus ASA in patients with heart failure who are in sinus rhythm, there was no overall difference in the risk of a composite of:329

  • Ischaemic stroke
  • Intracerebral haemorrhage
  • Death from any cause

There were:

  • 7.47 events per 100 patient-years in the warfarin group
  • 7.93 events per 100 patient-years in the ASA group (hazard ratio with warfarin, 0.93; 95% confidence interval, 0.79–1.10; p=0.40)

When analysed as a separate outcome, warfarin reduced the rate of ischaemic stroke relative to ASA:

  • 0.72 events per 100 patient-years in the warfarin group
  • 1.36 events per 100 patient-years in the ASA group (hazard ratio, 0.52; 95% confidence interval 0.33–0.82; p=0.005)

This benefit, however, was offset by a higher risk of bleeding:

  • 1.78 events per 100 patient-years in the warfarin group
  • 0.87 events per 100 patient-years in the ASA group (p<0.001)329

Given these findings, the authors suggested that the choice between warfarin and ASA should be individualized based on each patient’s specific circumstances.329

Anticoagulant therapy for patients with coronary artery disease and heart failure is under investigation – read more here.


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