Aspirin vs warfarin: which is better?

Taking aspirin to reduce blood-clotting is “as safe and just as effective as warfarin”, The Daily Telegraph has today reported. Both drugs have long been used to prevent potentially dangerous blood clots, but there is much debate over which is better for patients. Unfortunately, both can cause unpleasant side effects, such as major internal bleeds.

The news is based on a well-designed trial looking at aspirin and warfarin that compared their safety and effectiveness when treating patients who had heart failure but a normal heartbeat. Heart failure occurs when the heart can't pump enough blood around the body to meet its needs, leading to tiredness, shortness of breath and fluid retention. Anti-clotting medications such as aspirin or warfarin aren't always part of the standard medical treatment of heart failure, but they may be judged suitable for people who are also at increased risk of blood clots due to related problems such as cardiovascular disease.

During the study, 2,305 people with heart failure but no clear need to take anti-clotting drugs were randomly selected to take either warfarin or aspirin. Researchers found that there was no difference in the rate of clot-based strokes, bleeding in the brain or death in patients receiving aspirin compared with patients receiving warfarin. When strokes caused by clots (ischaemic strokes) were considered separately, warfarin was significantly better than aspirin at reducing the risk of stroke, although the rate of major bleeding was significantly higher with warfarin.

These findings provide a good indication that warfarin and aspirin are both comparable as treatments, at least in people with heart failure, a normal heart rhythm and no apparent high risk of clots. The findings do not alter the current medical management of heart failure or clot-prevention, so it is likely that the choice between prescribing warfarin and aspirin will continue to be made on a case-by-case basis.

Where did the story come from?

The study was carried out by researchers from Columbia University Medical Centre, New York, and several other international medical centres and universities. It was funded by the US National Institute of Neurological Disorders and Stroke. The study was published in the peer-reviewed New England Journal of Medicine.

The BBC and The Daily Telegraph both did accurate reports on this study.

What kind of research was this?

A range of conditions relating to the heart and circulatory system places individuals at greater risk of blood clots, which can be serious and even fatal. Blood clots can:

• block blood vessels connected to the lungs, causing "pulmonary embolism"
• block vessels to the brain, causing ischaemic stroke
• block vessels to the heart, causing a heart attack

To discourage blood clots, certain individuals may be placed on long-term courses of anti-blood-clotting drugs, including low-dose aspirin and warfarin.  

Both aspirin and warfarin have been shown to be effective at cutting the risk of dangerous blood clots, but both can cause side effects and have drawbacks. For example, both drugs can increase the risk of bleeding. In addition, dosages of warfarin need to be carefully controlled, as slightly too small a dose may not prove effective, but slightly too high a dose can greatly increase the risk of side effects, such as bleeding.

This new research was an international double-blind randomised controlled trial comparing the use of warfarin and aspirin in patients with heart failure but no heart rhythm problems. Heart failure refers to a condition where the heart can't pump enough blood around the body to meet its needs. Heart failure is a different, distinct condition from cardiac arrest (where the heart stops beating) and heart attack, where there is reduced blood flow to the heart. People with chronic heart failure can get tired and short of breath easily and often have fluid build-up in the ankles.

Rather than being a single disease, heart failure can be caused by a variety of underlying problems with the heart. Coronary heart disease (often leading to a heart attack) is the most common underlying cause of heart failure, but it can be caused by many other diseases such as heart rhythm problems, high blood pressure or heart valve disease. Anti-clotting medications such as aspirin or warfarin aren't always part of the standard medical treatment of heart failure, but they may be prescribed to people who are recognised to be at increased risk of blood clots due to a pre-existing condition such as cardiovascular disease or problems with their heart rhythm.

This study aimed to compare the “efficacy” of aspirin and warfarin for the treatment of patients with heart failure and normal heart rhythm who did not otherwise have a clear indication for taking either of these drugs. Efficacy means effectiveness within the controlled setting of a trial. A randomised controlled trial is the best type of study to address this question.

What did the research involve?

The researchers recruited 2,305 patients with heart failure and a normal heart rhythm, and randomised them to receive either warfarin or aspirin, in addition to any other medication to treat heart failure. Patients were judged to have heart failure on the basis they demonstrated “reduced left ventricular ejection fraction”, a phenomenon where the lower chamber on the left side of the heart pumps out less blood than it should as it beats.

Neither the patients nor the doctors that monitored them knew whether they were receiving warfarin or aspirin. This helped to ensure that their opinions, and therefore the results of the study, were unbiased. To achieve this, patients either received warfarin and a placebo (dummy pill) or aspirin and a placebo. Warfarin requires the blood to be able to clot in order for it to be monitored, and its dosage needs to be adjusted, if necessary, to meet a specific clotting target. Patients were followed up each month to monitor blood clotting and adherence to the drugs. Clinical examinations were performed every three months. Patients were followed up for at least one year, with an average follow-up time of three-and-a-half years.

The researchers analysed whether the rate of ischaemic strokes (stroke due to a blood clot), bleeding in the brain or death from any cause was different between the two groups. They also looked at the rate of heart attacks, hospitalisation for heart failure or any other major or minor bleeding in the body.

What were the basic results?

• Among the 2,305 participants, there were 531 deaths, 84 strokes and seven cases of bleeding in the brain during follow-up.
• The researchers found no significant difference in the rate of ischaemic stroke, bleeding in the brain or death from any cause between the patients receiving warfarin or those receiving aspirin (hazard ratio with warfarin 0.93, 95% confidence interval [CI] 0.79 to 1.10).
• The rates of heart attack and hospitalisation for heart failure did not differ significantly between the two groups.
• When ischaemic stroke by itself was considered, warfarin was better than aspirin at reducing risk of stroke (HR 0.52, 95% CI 0.33 to 0.82).
• However, the rate of major bleeding was significantly higher with warfarin (adjusted rate ratio 2.05, 95% CI 1.36 to 3.12).

How did the researchers interpret the results?

The researchers concluded that, given the finding that warfarin did not provide an overall benefit and was associated with an increased risk of bleeding, there is “no compelling reason” to prescribe warfarin rather than aspirin for patients with a reduced left ventricular ejection fraction and normal heart rhythm. They also stated that: “The choice between warfarin and aspirin should be individualised.”

Conclusion

This well-designed trial has compared the efficacy and safety of aspirin and warfarin in patients with heart failure, a normal heartbeat and no clear medical condition requiring anti-clotting medication. In these patients, the study found that there was no difference in the rate of ischaemic strokes, bleeding in the brain or death from any cause between the two groups. The rates of heart attack and hospitalisation for heart failure also did not differ significantly between the two groups. When stroke was considered by itself, warfarin was significantly better than aspirin. However, the rate of major bleeding was significantly higher with warfarin. This study has shown that neither drug has a clear advantage over the other in people with heart failure but a normal heart rhythm who do not have a recognised increased risk of blood clots.

But although the number of strokes in this study was significantly reduced with warfarin, the number of strokes in each group was low: 0.72 strokes per 100 years of patient follow-up in the warfarin group compared with 1.36 strokes per 100 years of patient follow-up in the aspirin group. The increase in major bleeding observed with warfarin was mostly due to bleeding in the gut. Previous studies have found that mild-to-moderate heart failure is associated with an annual stroke risk of approximately 1.5%, and severe heart failure is associated with a risk of approximately 4%, compared with a risk of 0.5% in the general population. A recent Cochrane review concluded that the data available does not support the routine use of oral anticoagulation in patients with heart failure and a normal heartbeat.

These findings do not alter the current medical management of heart failure. There are various reasons why a person with heart failure may be identified to be at increased risk of blood clots, including people who have underlying cardiovascular disease (which could include a past heart attack or stroke), an abnormal heart rhythm or heart valve disease.

Overall, it is likely that the decision as to whether or not to treat heart failure patients with anti-clotting drugs (and subsequently whether to choose between aspirin and warfarin) will continue to be made on a case-by-case basis. When making their decision, doctors will continue to weigh up the benefits of, for example, reducing the risk of stroke against the risks of side effects, such as an increased risk of bleeding.