Warfarin No Better Than Aspirin for Most Heart Failure Patients

Results of one of the largest studies of heart failure to date show that warfarin is no better than aspirin in reducing the combined risks of brain hemorrhage, stroke and death in most heart failure patients.

The research, reported May 2 in the New England Journal of Medicine, looked at heart failure patients with a normal heart rhythm.

The results show that the combined rate of death, stroke and brain hemorrhage was not statistically different between the two groups, at 7.47 percent per year for patients taking warfarin and 7.93 percent per year for those taking aspirin.

Heart failure is a condition in which the heart can’t pump enough blood to the body. A weakened heart increases the risk of blood clots that can cause a fatal or disabling stroke. Both aspirin and warfarin reduce the risk of stroke, but they do so by different mechanisms and with different risks.

“For the first time, clinicians have reassurance that they don’t need to put people with heart failure who have a normal rhythm on anticoagulants like warfarin, which increase the risk of bleeding,” says co-author Douglas L. Mann, MD, chief of the cardiovascular division at School of Medicine in St. Louis, who treats patients at Barnes-Jewish Hospital. “We can give patients aspirin and be reassured that it’s not going to either worsen the heart failure or lead to increased risk of death.”

The decade-long WARCEF trial (Warfarin and Aspirin for Reduced Cardiac Ejection Fraction) followed 2,305 patients and compared the anticoagulant warfarin, known by the brand name Coumadin, to aspirin. Previous studies have shown that warfarin is superior to aspirin for preventing stroke in heart failure patients with atrial fibrillation, a common irregular heart beat. WARCEF is the first study to compare warfarin to aspirin for most heart failure patients – those with a normal heart rhythm.

Patients enrolled in the trial were randomly assigned to one of two groups. One group received aspirin and placebo warfarin. A second group received warfarin and placebo aspirin. Neither the patients nor clinicians knew which active drug a particular patient received until the end of the study. Since patients on warfarin require regular blood tests, all patients’ blood was monitored whether or not they were taking active warfarin.

With at least 6 million Americans living with heart failure, this study answers an important clinical question. 

“Since the overall risks and benefits are similar for aspirin and warfarin, the patient and his or her doctor are free to choose the treatment that best meets their particular medical needs,” says principal investigator Shunichi Homma, MD, of Columbia University Medical Center/New York-Presbyterian Hospital. “However, given the convenience and low cost of aspirin, many may go this route.”

Aspirin makes blood cells called platelets less “sticky,” reducing their ability to clump together and form clots. Downstream of this, warfarin interferes with chemical reactions in the body’s so-called “coagulation cascade,” thereby reducing clotting. While warfarin is associated with a greater risk of bleeding, aspirin may inhibit other medications frequently prescribed to heart failure patients. Unlike aspirin, warfarin requires a prescription and patients must have regular blood tests to monitor clotting levels. 

While the study found no difference in the combined risk of brain hemorrhage, stroke and death, the two drugs did differ in the risks of individual problems. Specifically, patients taking warfarin had almost half the risk of stroke compared to those taking aspirin. And patients taking warfarin had more than twice the risk of major bleeding. According to the investigators, these results cancel each other out, and point to the importance of tailoring the treatment to individual patients.

“The key decision will be whether to accept the increased risk of stroke with aspirin or the increased risk of primarily gastrointestinal hemorrhage with warfarin,” says Walter Koroshetz, MD, deputy director of the National Institute for Neurological Disorders and Stroke, which supported the trial.

However, in patients followed four years or longer, there was evidence that warfarin was more effective overall in preventing deaths, strokes and cerebral hemorrhages.

“As we analyze the data further, we hope to be able to identify whether some patients will clearly benefit from one drug versus the other over time,” Mann says.