Warfarin vs Aspirin for Heart Failure: WARCEF Trial Results

Author: American Stroke Association
Published: 6 Feb 2012 - Updated: 23 Sep 2026
Publication Type: Findings

Table of Contents:
Synopsis - Definition - Overview - FAQs - Insights, Updates - Related Content

Synopsis

This research reports on the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial, the largest and longest head-to-head comparison of the two anti-clotting drugs, presented at the American Stroke Association's International Stroke Conference 2012. Researchers across 11 countries followed 2,305 heart failure patients with normal heart rhythm, averaging 61 years of age and with a left ventricular ejection fraction below 35 percent, for up to six years. Patients received either 325 mg of aspirin daily or carefully dosed warfarin, and the combined rate of death, ischemic stroke, or brain hemorrhage was 7.47 percent on warfarin and 7.93 percent on aspirin - a difference that was not statistically significant. Led by Dr. Shunichi Homma of Columbia University and funded by the National Institutes of Health, the study gives people living with heart failure, older adults, and their doctors solid evidence for weighing the benefits of each drug against its risks, with the lead author concluding there is no compelling reason to choose warfarin over aspirin for most of these patients.*

At a Glance

• 1 - Brain bleeds were rare, at 0.12 percent a year on warfarin and 0.05 percent on aspirin.
• 2 - Major bleeding occurred in 1.8 percent of warfarin patients each year, double the 0.9 percent rate on aspirin.
• 3 - Warfarin patients were about half as likely to have a stroke, with annual rates of 0.72 percent versus 1.36 percent.
• 4 - All patients had blood drawn on the same schedule so neither they nor their doctors knew which drug they were taking.

Topic Definition

Anticoagulant Therapy in Heart Failure

Anticoagulant therapy in heart failure is the use of blood-thinning medications to lower the risk of dangerous clots in people whose hearts pump less effectively than normal. When the heart's main pumping chamber is weakened, blood can move sluggishly and form clots that may travel to the brain and cause a stroke. Treatment options range from antiplatelet drugs such as aspirin, which keep platelets from clumping, to anticoagulants such as warfarin, which interfere with the body's clotting proteins. Choosing between them means balancing the protection each offers against its bleeding risk, the need for blood monitoring, and the patient's overall health and heart rhythm.

Overview

In the largest and longest head-to-head comparison of two anti-clotting medications, warfarin was similar to aspirin in preventing deaths and strokes in patients with heart failure with normal heart rhythm.

Although there was no difference for the overall study, there was greater benefit of warfarin among patients followed for four or more years. Bleeding episodes were more common with warfarin than aspirin, but dangerous bleeding in the brain occurred at low levels in both groups.

In the largest and longest head-to-head comparison of two anti-clotting medications, warfarin, and aspirin were similar in preventing deaths and strokes in heart failure patients with normal heart rhythm, according to late-breaking research presented at the American Stroke Association's International Stroke Conference 2012.

"Although there was a warfarin benefit for patients treated for four or more years, overall, warfarin, and aspirin were similar," said Shunichi Homma, M.D., lead author of the study and the Margaret Milliken Hatch Professor of Medicine at Columbia University in New York.

In the 11-country Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial, researchers followed 2,305 patients with heart failure and normal heart rhythm for up to six years (average 3.5 years). The patients were on average 61 years old, and the power of the heart's main pumping chamber, the left ventricle (left ventricular ejection fraction), was less than 35 percent (normal is 55 percent or higher).

Thirteen percent of the patients experienced a stroke or transient ischemic attack and were at heightened risk of recurrence. Patients with heart failure in general are at increased risk of death, blood clots and strokes.

Researchers randomly assigned patients to receive either 325 mg/day of aspirin or warfarin doses calibrated to a pre-specified level of blood thinning. Warfarin therapy requires frequent blood testing to monitor its dosage to achieve the desired level of blood thinning. To avoid bias, all patients had blood drawn on the same schedule and their pills adjusted so neither the patients nor their treating physicians knew which regimen they were taking.

Death, ischemic stroke (caused by blockage of an artery feeding the brain) or intracerebral hemorrhage (bleeding inside the brain), which combined were the study's primary endpoint, occurred at 7.47 percent for patients assigned to warfarin and 7.93 percent for patients assigned to aspirin. The difference was not statistically significant.

However, "in the group of patients followed for more than three years, those on warfarin did better in comparison to the aspirin patients," Homma said.

Over the entire study period, patients receiving warfarin were just over half as likely to develop a stroke, a component of the primary endpoint, as those taking aspirin. The rates of stroke were low, with annual rates of 0.72 percent in patients assigned to warfarin and 1.36 percent for those on aspirin.

Researchers evaluated the safety of the anti-clotting medications by monitoring major bleeding events apart from intracerebral hemorrhage (which was a component of the primary endpoint). Each year, major bleeds occurred in 1.8 percent of patients on warfarin and 0.9 percent of those on aspirin - a statistically significant difference.

"As expected, the overall bleeding rate was higher with warfarin," Homma said. "However, not all bleeds are equal, and the one that patients fear the most - bleeding within the brain (intracerebral hemorrhage) rarely occurred in both groups." It occurred in 0.12 percent per year in the warfarin group and 0.05 percent per year in the aspirin group.

"Given that there is no overall difference between the two treatments and that possible benefit of warfarin does not start until after 4 years of treatment, there is no compelling reason to use warfarin, especially considering the bleeding risk", Homma said. The investigators are analyzing whether certain subgroups of patients benefited more from each treatment.

• The study's co-author is John L.P. Thompson, Ph.D. and the WARCEF Investigators.
• Author disclosures are on the abstract.
• The National Institutes of Health/National Institute of Neurological Disorders and Stroke funded the study.

Statements and Conclusions

Statements and conclusions of study authors that are presented at American Stroke Association scientific meetings are solely those of the study authors and do not necessarily reflect association policy or position. The association makes no representation or warranty as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and funds specific association programs and events. The association has strict policies to prevent these relationships from influencing science content.

Frequently Asked Questions

NOTE: Researched FAQs by Disabled World (DW)

What is the difference between how aspirin and warfarin prevent clots?

Aspirin is an antiplatelet drug that stops platelets from sticking together, while warfarin is an anticoagulant that blocks vitamin K dependent clotting factors made in the liver.

Why does warfarin require regular blood tests?

Warfarin has a narrow safe range, so doctors check the INR blood test regularly to make sure the blood is thin enough to prevent clots but not so thin that it causes bleeding.

Do foods affect how warfarin works?

Yes. Foods high in vitamin K, such as kale, spinach, and broccoli, can reduce the effect of warfarin, so patients are usually advised to keep their intake steady rather than avoid these foods.

Are there newer alternatives to warfarin?

Yes. Direct oral anticoagulants such as apixaban, rivaroxaban, dabigatran, and edoxaban are now widely used for some conditions and generally do not need routine blood monitoring.

What is ejection fraction and why does it matter?

Ejection fraction is the percentage of blood the left ventricle pumps out with each beat. A lower number means a weaker heart, which raises the risk of clots, stroke, and other complications.

Does atrial fibrillation change the choice of blood thinner?

Yes. Heart failure patients who also have atrial fibrillation face a much higher stroke risk, and guidelines generally recommend an anticoagulant rather than aspirin alone for them.

What are the warning signs of serious bleeding on a blood thinner?

Warning signs include black or bloody stools, vomiting blood, blood in the urine, severe headache, sudden weakness, unusual bruising, or bleeding that will not stop, all of which need prompt medical care.

Should I stop taking aspirin or warfarin on my own?

No. Stopping a blood thinner suddenly can raise the risk of a clot or stroke, so any change should only be made with guidance from your doctor.

Insights, Analysis, and Developments

Editorial Note: The WARCEF findings carry a quiet but important message for anyone managing heart failure: a more complicated, more closely monitored drug is not automatically the better choice. Warfarin did show an edge for patients treated four years or longer, and it cut stroke risk nearly in half, but those gains came with more bleeding and the burden of frequent blood tests - a real consideration for older adults, people with mobility limitations, and those who find regular lab visits difficult. About 13 percent of participants had already had a stroke or mini-stroke, a reminder of how closely heart failure and stroke are linked. Since this trial, newer anticoagulants have entered the picture and treatment guidelines have continued to evolve, so the best path forward is a personal conversation with a cardiologist about bleeding risk, stroke history, and how long treatment is likely to last.*

Attribution/Source(s): This quality-reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by American Stroke Association and published on 6 Feb 2012, this content may have been edited for style, clarity, or brevity.

* Editorial additions by Ian C. Langtree.