By Oscar Millan Iturbe MD/MPH @ozkr_millan
I would like to comment the new study led by Dr Shunichi Homma and Dr John (Seamus) Thompson, the use of warfarin or aspirin have been compared for thromboprophylaxsis in patients with heart failure (HF) and sinus rhythm. On the basis of their findings, the investigators conclude that “there is no compelling reason to use warfarin rather than aspirin in patients with a reduced left ventricular ejection fraction who are in sinus rhythm.”
In total, 2,305 patients from 168 centers in 11 countries were enrolled in the double-blind, double-dummy, randomized WARCEF trial. The mean left ventricular ejection fraction for the enrolled patients was 24.7%. Mean follow-up time was 3.5 years. Total follow-up time was 8,225 patient-years. Patients in the warfarin group had an INR in the therapeutic range (2.0–3.5) for 63% of the total treatment time.
The primary outcome—first incidence of ischemic stroke, intracerebral hemorrhage, or death—occurred at rates of 7.47 and 7.93 events per 100 patient-years in the warfarin and aspirin groups, respectively (HR for warfarin 0.93, 95% CI 0.79–1.10, P = 0.40). Although no significant difference was observed overall, time-varying analysis did demonstrate a small benefit of warfarin over aspirin with time, which was statistically significant by year 4 (HR for warfarin 0.76, P = 0.04). However, the investigators point out that this benefit “was of borderline statistical significance and uncertain clinical significance”.
The rates of death, intracerebral hemorrhage, myocardial infarction, and hospitalization for HF did not differ significantly between the two treatment groups. Warfarin was associated with approximately half as many ischemic strokes, but twice as many major hemorrhages and gastrointestinal bleeds, and ~50% higher rates of minor hemorrhage compared with aspirin.
“We will look for a subgroup that may benefit from warfarin or aspirin, so that one can tailor the therapy,” says Dr Homma. The WARCEF investigators also point out in their report that newer antithrombotic agents might prove to be more effective than either of the agents compared in this trial. Indeed, Dr Homma tells us that they are planning to test the newer antithrombotic agents in these patients.
- Homma, S. et al. Warfarin and aspirin in patients with heart failure and sinus rhythm. N. Engl. J. Med. doi: 10.1056/NEJMoa1202299