Aspirin Without an Indication Comes with More Risk than Reward in Patients on DOACs

Jordan Schaefer, MD

Considering a DOAC in a patient with atrial fibrillation? New research suggests use of concomitant aspirin without a clear indication might unnecessarily increase risk of bleeding compared to DOAC monotherapy.

An analysis of patients treated at 4 clinics in Michigan, results indicate patients receiving both a DOAC and aspirin had a greater risk of bleeding events and hospitalization while also providing evidence suggesting nearly 1-in-3 patients with atrial fibrillation (AF) or venous thromboembolism (VTE) who received DOAC and acetylsalicylic acid (ASA) received the latter without a clear indication.

"The patients on combination therapy were more likely to have bleeding events but they weren't less likely to have a blood clot," said lead investigator Jordan Schaefer, MD, an assistant professor of internal medicine and a hematologist at Michigan Medicine, the academic medical center of the University of Michigan, in a statement. "Therefore, it's important that patients ask their doctors if they should be taking aspirin when they are prescribed a direct oral anticoagulant."

While newer agents such as apixaban, dabigatran, edoxaban, and rivaroxaban have been improving the prognosis of patients with AF and VTE for more than a decade now, some knowledge gaps related to real-world use still exist. With this in mind, Schaefer and a team of colleagues from Michigan-based Institutions designed a registry-based cohort study to evaluate the frequency and outcomes of prescription of concomitant ASA and DOAC therapy amount patients with AF and/or VTE.

For their study population, investigators obtained data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI), which included the creation of a registry of adult patients transitioning to a DOAC from warfarin at 4 medical centers in Michigan. Using data collected from January 2015-December 2019, investigators identified a cohort of 3280 patients for inclusion in their study.

Overall, the study cohort was 51% (n=1673) men, the mean age was 68.2 (SD, 13.3) years, and the mean follow-up was 20.9 (SD, 19.0) months. Of note, all patients included in the study had at least 3 months of follow-up, had no history of myocardial infarction in the 6 months prior to DOAC initiation, and had no history of heart valve replacement.

Of the 3280 patients included in the study, 33.8% (n=1107) had no clear indication for ASA and were being treated with DOACS and ASA. Initial analyses indicated the percentage of patients on combination therapy did not change significantly during the study period and low-dose ASA was used by 90.1% of patients on concomitant ASA.

For the purpose of analysis, investigators created a pair of propensity score-matched cohorts of 1047 defined by use of DOAC monotherapy or DOAC plus ASA. The primary outcomes of interest for these analyses were rates of bleeding, rates of thrombosis, emergency department visits, hospitalizations, and death. Investigators stratified bleeding events as any, nonmajor, and major and thrombosis as stroke, VTE, and MI.

When comparing rates of bleeding events among the groups, results indicated patients taking DOAC and ASA experienced a greater rate of any events than those on DOAC monotherapy (26.0 vs 31.6 per 100 patient years, P=.01). When assessing specific types of events, investigators found combination therapy was associated with a significantly higher rate of nonmajor bleeding (26.1 vs 21.7 per 100 patient years, P=.02) compared to DOAC monotherapy, but major bleeding rates were similar between the cohorts (4.95 vs 3.59 per 100 patient years, P=.09).

Rate of thrombotic events was overall low and similar between the study arms with rates of 2.5 and 2.3 events per 100 patient years, respectively, among patients on combination therapy and DOAC monotherapy (P=.80).

When assessing hospitalization rates, results indicated hospitalizations occurred more often in patients on combination therapy compared to those on DOAC monotherapy (9.1 vs 6.5 admissions per 100 patient years, P=.02), but investigators pointed out this was driven by an increased rate of hospitalization for bleeding between the study arms (8.2 vs 5.30 admissions per 100 patient years, P=.006).

This study, “Adverse Events Associated With the Addition of Aspirin to Direct Oral Anticoagulant Therapy Without a Clear Indication,” was published on JAMA Internal Medicine.