Warfarin-aspirin therapy associated with increased bleeding compared with warfarin only

Patients with atrial fibrillation or venous thromboembolism who received aspirin without a clear therapeutic indication in addition to warfarin had higher rates of bleeding and similar rates of thrombosis.


Combining aspirin therapy with warfarin without a clear therapeutic indication to do so was associated with increased bleeding and similar rates of thrombosis as warfarin monotherapy, a study found.

The registry-based cohort study enrolled 6,539 adults at six anticoagulation clinics in Michigan from 2010 to 2017 who were receiving warfarin therapy for atrial fibrillation or venous thromboembolism without documentation of a recent myocardial infarction or history of valve replacement. Aspirin was prescribed without a clear therapeutic indication to 2,453 patients (37.5%). Rates of any bleeding, major bleeding events, ED visits, hospitalizations, and thrombotic events were recorded at one, two, and three years. Study results were published by JAMA Internal Medicine on March 4.

Data from two propensity score-matched cohorts of 1,844 patients were analyzed (warfarin and aspirin compared to warfarin only). At one year, patients receiving combination warfarin and aspirin, compared with those receiving warfarin only, had higher rates of overall bleeding (cumulative incidence, 26.0% [95% CI, 23.8% to 28.3%] vs. 20.3% [95% CI, 18.3% to 22.3%]; P<0.001), major bleeding (5.7% [95% CI, 4.6% to 7.1%] vs. 3.3% [95% CI, 2.4% to 4.3%]; P<0.001), ED visits for bleeding (13.3% [95% CI, 11.6% to 15.1%] vs. 9.8% [95% CI, 8.4% to 11.4%]; P=0.001), and hospitalizations for bleeding (8.1% [95% CI, 6.8% to 9.6%] vs. 5.2% [95% CI, 4.1% to 6.4%]; P=0.001).

Rates of thrombosis were similar between groups, with a one-year cumulative incidence of 2.3% (95% CI, 1.6% to 3.1%) for those receiving combination warfarin and aspirin therapy and 2.7% (95% CI, 2.0% to 3.6%) for those receiving warfarin alone (P=0.40). Similar findings persisted during three years of follow-up, as well as in sensitivity analyses.

Clinicians should be judicious in selecting patients for combination therapy, the authors concluded. “Similar to other studies published for more than a decade, we did not observe any clinical benefit of aspirin being prescribed with warfarin therapy,” they wrote. “Unfortunately, the rate of combined warfarin and aspirin use has not declined as a result of those findings, emphasizing the need for greater awareness of this issue and efforts to discontinue aspirin therapy in these patients, especially low-risk patients.”