Aspirin and warfarin: Should they be used together?

DURHAM, NORTH CAROLINA. Despite little evidence of benefit, millions of people around the world are taking an aspirin every day in order to ward off a first heart attack or ischemic stroke. Although the “daily aspirin ritual” is considered innocuous, it is anything but. A recent meta-analysis of 5 clinical trials comparing aspirin to placebo showed that long-term aspirin usage increases the relative risk of suffering a hemorrhagic stroke by about 40% and the risk of major gastrointestinal bleeding by 70%.

A Japanese clinical trial investigating the benefits of aspirin in low-risk atrial fibrillation (AF) patients found that there were actually more cardiovascular deaths, strokes and TIAs in the aspirin group than in the placebo group. In addition, fatal or major bleeding was found to be more frequent in the aspirin group than in the placebo group. Overall, the incidence of strokes, deaths and other adverse events was 42% greater in the aspirin group than in the placebo group. The trial was stopped early since the probability that aspirin would prove superior to placebo in stroke prevention, if it continued, was deemed to be vanishingly small.

It is well established that combining aspirin and warfarin therapy in AF patients increases the risk of major bleeding. Thus, it is surprising that a recent study found that 35% of AF patients prescribed warfarin for stroke prevention had also been prescribed aspirin. The study was part of the ORBIT-AF study and involved 7347 AF patients on oral anticoagulation with warfarin. Of the 35% of study participants prescribed both warfarin and aspirin, 39% had no atherosclerosis or other condition that would warrant prescribing aspirin in addition to warfarin. Conversely, 37% of patients with known cardiovascular disease who might benefit from added aspirin were only prescribed warfarin. Furthermore, a significant proportion of patients prescribed both warfarin and aspirin was known to have elevated bleeding risk. Not surprisingly, patients prescribed both warfarin and aspirin had a relative 50% greater risk of being hospitalized for major bleeding and a 3-fold increased risk of suffering a hemorrhagic stroke when compared to patients on warfarin only. These finding confirm earlier results from a Danish study which concluded that combining warfarin and aspirin doubles the risk of bleeding events when compared to warfarin alone.

The authors of the Duke University study conclude that physicians prescribing warfarin or one of the newer anticoagulants to AF patients need to carefully consider the benefit/risk ratio of adding aspirin.
Steinberg, BA, et al. Use and associated risks of concomitant aspirin therapy with oral anticoagulation in patients with atrial fibrillation. Circulation, Vol. 128, August 13, 2013, pp. 721-28
Patrono, C and Andreotti, F. Antithrombotic therapy for patients with atrial fibrillation and atherothrombotic vascular disease. Circulation, Vol. 128, August 13, 2013, pp. 684-86 (editorial)

Editor’s comment: This study adds to the proof that aspirin, whether used on its own or in combination with warfarin, is not innocuous and should be used with caution in AF patients. One of the authors of the study, Dr. Eric Peterson put it this way, “In general, if I see a patient in my clinic who has only atrial fibrillation and no other risk factors, they should not be on aspirin because I know for sure their risk of bleeding is going to be one and a half times what it was before.”

As far as the “daily aspirin ritual” in general is concerned, the US Preventive Services Task Force has this advice, “Patients at low risk for coronary heart disease probably do not benefit from and may even be harmed by aspirin because the risk for adverse events may exceed the benefits.”

NOTE: Discontinuing long-term use of aspirin may temporarily increase risk of stroke and TIA. For more on this see.