The Hospice Clinician Blog

In the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) study, published last week in the New England Journal of Medicine, aspirin was found to be as good as warfarin in the prevention of a composite end point of CVA or death from any cause in patients with heart failure who are in sinus rhythm.

Heart failure often coexists with atrial fibrillation, which increases the risk of stroke. But heart failure is also independently associated with an increased risk of thrombosis even when patients are in normal sinus rhythm. For this reason, heart failure patients are often treated with anticoagulant and/or antiplatelet medications. However, the role of oral anticoagulants as compared with aspirin has not been clarified in clinical trials, which previously have been confounded by the presence of atrial fibrillation in many patients, have been restrospective in nature, or have recruited too few patients to produce conclusive results.

This double-blind, double-dummy study was conducted at 168 centers in 11 countries and followed 2305 patients, average age 61, for up to 6 years. Eligible patients had a left ventricular ejection fraction of 35% or less (average LVEF in both groups was 25%) and were in normal sinus rhythm. The majority of patients had NYHA Class II or III heart failure (moderate-severe). Patients were randomized to receive either aspirin 325 mg daily or warfarin to a target INR of 2.0 – 3.5.

The primary outcome was the time to first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. There was no difference between the two groups in the primary outcome (warfarin group: 7.47 events per 100 patient-years; aspirin: 7.93 events per 100 patient-years; P = 0.40). There was a statistically significant reduction in the rate of ischemic stroke in the warfarin group (warfarin: 0.72 events per 100 patient-years; aspirin 1.36 events per 100 patient-years, P = 0.005), but this was offset by an increased risk of major hemorrhage in the warfarin group (warfarin: 1.78 events per 100 patient-years; aspirin: 0.87 events per 100 patient-years; P < 0.001). In summary, the authors concluded that there is “no compelling reason” to use warfarin rather than aspirin in patients with heart failure who are in normal sinus rhythm.

When being used strictly for prophylaxis, we usually recommend that all antiplatelet and/or anticoagulant therapy be discontinued once a patient comes on hospice due to risks outweighing benefits. However, the reality is that many patients continue their antiplatelet and/or anticoagulant therapy, even until their final days. While we cannot directly apply the results of this study to hospice patients with heart failure, since only a small portion of the study population had NYHA Class IV heart failure, we can view the results of this study as giving us reason to consider switching from warfarin to aspirin in patients with heart failure who are in normal sinus rhythm and who wish to continue thromboprophylactic therapy. Warfarin becomes increasingly difficult to manage at the end of life and switching to aspirin may help reduce the risk of serious adverse events in many patients.

Reference:

Homma S, Thompson JLP, Pullicino PM, et al. Warfarin and aspirin in patients with heart failure and sinus rhythm. NEJM. Published online on May 2, 2012 at NEJM.org.