Adding aspirin or NSAID to anticoagulant doubles bleeding risk

Taking aspirin or an NSAID while on anticoagulant therapy significantly increases the risk of bleeding in patients who have had a venous thromboembolism (VTE), a recent study found.


Taking aspirin or an NSAID while on anticoagulant therapy significantly increases the risk of bleeding in patients who have had a venous thromboembolism (VTE), a recent study found.

Researchers conducted a prospective analysis of observational data from the EINSTEIN trials, which compared anticoagulant treatment with oral rivaroxaban with initial enoxaparin followed by vitamin K antagonist (VKA) therapy in more than 8,000 patients with deep venous thrombosis or pulmonary embolism between 2007 and 2009. The researchers looked at days of aspirin or NSAID use while patients were on one of the anticoagulants and instances of clinically relevant or major bleeding. Results were published April 14 by JAMA Internal Medicine.

Taking NSAID or aspirin while on an anticoagulant significantly increased the risk of either type of bleeding compared to taking an anticoagulant alone. With NSAIDs, there were 37.5 clinically relevant bleeding events and 6.5 major bleeds per 100 patient-years compared to 16.6 and 2.0, respectively, in those not taking NSAIDs (hazard ratio [HR] for clinically relevant bleeding events, 1.77; 95% CI, 1.46 to 2.14 and HR for major bleeds, 2.37; 95% CI, 1.51 to 3.75). For patients on aspirin, the risk of clinically relevant bleeding was 36.6 per 100 patient-years, compared to 16.9 per 100 patient-years not on aspirin (HR, 1.70; 95% CI, 1.38 to 2.11). Major bleeding rates were 4.8 per 100 patient-years in aspirin-taking patients compared to 2.2 during aspirin nonuse (HR, 1.50; 95% CI, 0.86 to 2.62).

The authors concluded that in patients on anticoagulant therapy due to a VTE, concomitant use of an NSAID or aspirin is associated with about a doubling of the risk of bleeding. They noted that bleeding rates were similar on either of the anticoagulant regimens (rivaroxaban or enoxaparin-VKA) and that the study wasn't powered to determine whether use of selective COX-2 NSAIDs reduced the risk of bleeding.

Even though the study protocol discouraged physicians from using NSAIDs or aspirin, 22% of the participating patients took NSAIDs at some point during follow-up. Combined with the exclusion of patients with increased bleeding risk from the trial, this indicates that the study results may actually underestimate the bleeding risk of combining these drugs in practice. The study authors urged physicians “to combine anticoagulation with either NSAID or aspirin therapy with caution and only if genuinely indicated, with no similarly effective and safer alternative treatment available.”