Younger Heart Failure Patients May Benefit from Warfarin

Heart failure patients younger than 60 years of age who took warfarin experienced significantly fewer adverse events than those who took aspirin, a new study finds.

Warfarin may be more beneficial than aspirin in preventing ischemic stroke, intracerebral hemorrhage, and death in younger heart failure patients, according to the results of a study published online on July 23, 2013, in Circulation: Heart Failure.

The study was a sub-analysis of the Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction trial. The original trial randomly assigned 2305 patients with reduced left ventricular ejection fraction in sinus rhythm from 11 different countries to receive warfarin or aspirin daily for a median follow-up period of 3.4 years. Its results indicated no difference between warfarin and aspirin for the primary outcome of ischemic stroke, intracerebral hemorrhage, or death.

The new analysis investigates whether any subgroups, including participants categorized by criteria such as age, gender, body mass index, race, and ethnicity, benefit more from receiving warfarin or aspirin.

After adjusting for other factors, age was the only variable associated with a difference in risk for ischemic stroke, intracerebral hemorrhage, or death depending on whether participants took warfarin or aspirin. Patients younger than 60 receiving warfarin experienced on average 4.81 events per 100 patient-years compared with 6.76 events per 100 patient-years in comparable patients receiving aspirin. No difference for these outcomes was observed in patients older than 60 based on whether they were taking warfarin or aspirin.

When major hemorrhage was added to the outcomes in a secondary analysis, patients younger than 60 receiving warfarin still had a significantly lower combined event rate than those taking aspirin: 5.41 per 100 patient-years compared with 7.25 per 100 patient-years. Conversely, when major hemorrhage was added to the outcomes for patients older than 60, warfarin users experienced 11.8 events per 100 patient-years compared with 9.35 events per 100 patient-years in aspirin users.

The researchers also calculated the difference in risk of experiencing each outcome depending on whether a patient was taking warfarin or aspirin. Both older and younger patients taking warfarin experienced a reduced risk of ischemic stroke compared with those taking aspirin. Taking warfarin was associated with lower death rates for those younger than 60, but higher death rates for those older than 60. No significant difference in the risk of intracerebral hemorrhage was observed in either age group depending on medication used. In the younger age group, there was no significant difference between warfarin and aspirin in the rate of major hemorrhages. Among the older age group, however, significantly more hemorrhages occurred in those receiving warfarin.

Overall, patients younger than 60 receiving warfarin had an absolute yearly risk reduction of 1.95%. If applied to the entire United States heart failure patient population, this would translate to approximately 15,005 events avoided overall, including 5617 strokes, 10,157 deaths, and 769 intracerebral hemorrhages.

Despite the large reductions found in their analysis, the authors note that more research is needed to verify the accuracy of their findings. “Although our findings may have a large public health impact, they require confirmation in a future trial,” they write. “Also, given the possible benefit of warfarin in the younger population, the role of new anticoagulants needs to be established.”