Adding aspirin to direct oral anticoagulant therapy may lead to more bleeding events
ORLANDO — The addition of aspirin to direct oral anticoagulant therapy for venous thromboembolism or nonvalvular atrial fibrillation appeared associated with increased rates of bleeding events compared with use of the anticoagulants alone, according to results of a registry-based cohort study presented at ASH Annual Meeting at Exposition.
Further, aspirin did not appear to reduce incidence of thrombosis compared with direct oral anticoagulant (DOAC) therapy alone.
Adding aspirin to therapy with direct oral anticoagulants usually is appropriate after a patient experiences acute coronary syndromes or percutaneous coronary intervention. However, many patients receive DOACs and aspirin without a clear need for the combination regimen, according to researchers.
“Aspirin is an over-the-counter drug, so many people are on it for the ordinary prevention of heart disease, whether that was prescribed by their doctor, they saw it on a television commercial or because they read about its potential benefits,” Jordan K. Schaefer, MD, hematologist and assistant professor in the division of hematology/oncology at University of Michigan, told Healio. “Down the line, they may have been prescribed to an anticoagulant for a different reason, and it’s possible nobody looked back and stopped the aspirin or thought about whether they need to be on both.”
Previous studies have shown that adding aspirin to warfarin may increase risks for bleeding without reducing thrombotic events. However, it remained unclear whether aspirin could have the same effect in combination with DOACs.
For that reason, Schaefer and colleagues analyzed the impact of adding aspirin, without a clear indication to do so, to DOAC therapy among a cohort of 2,045 patients taking DOACs for VTE or nonvalvular atrial fibrillation. Researchers recruited patients through the Michigan Anticoagulation Quality Improvement Initiative.
Among the patients, 647 who did not have a clear indication for aspirin received it with a DOAC.
Researchers compared two groups of 639 propensity score-matched patients who received DOAC monotherapy (median age, 71.6 years) or a DOAC in combination with aspirin (median age, 71.8 years). About two-thirds of patients received the DOAC apixaban (Eliquis; Bristol-Myers Squibb, Pfizer), whereas about one-third received rivaroxaban (Xarelto; Janssen, Bayer). Most patients (87%) received high-dose DOAC therapy.
Researchers excluded patients with a history of heart valve replacement, recent myocardial infarction or less than 3 months of follow-up.
Any new bleeding event served as the study’s primary endpoint. Secondary endpoints included new episodes of arterial or VTE, fatal bleeds, life-threatening bleeds, major bleeds, clinically relevant nonmajor bleeds, nonmajor bleeds, intracranial or intraspinal bleeds, or death.
Median follow-up was 15.2 months.
Results showed that patients on combination therapy had a higher rate of new bleeding events than patients on DOAC monotherapy (319 events vs. 261 events; P = .02).
The difference in bleeding events was driven largely by clinically relevant nonmajor bleeds (combination therapy, n = 151 vs. monotherapy, n = 109; P = .01). Two fatal bleeding events, however, occurred in the monotherapy group, compared with none in the combination group.
Common bleeding sites were cutaneous, gastrointestinal and genitourinary.
Observed rates of thrombosis, including stroke, VTE, myocardial infarction or other, appeared similar between groups (combination therapy, n = 19 vs. monotherapy, n = 18).
Patient on combination therapy had more ED visits than patients in the monotherapy group (145 vs. 118), but the difference did not reach statistical significance.
“One of the limitations of our study was the size,” Schaefer said. “We need to have larger studies that follow patients for a long period of time to analyze the events of clotting and bleeding. This will help settle the issue of who may benefit from being on both drugs compared with who may benefit from being on just one.”– by John DeRosier
Schaefer J, et al. Abstract 787. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2019; Orlando.
Disclosures: Schaefer reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.