Orlando, Florida—The addition of aspirin to direct oral anticoagulants (DOACs) in patients with venous thromboembolism (VTE) or non-valvular atrial fibrillation (NVAF) resulted in more bleeding events without significant improvement in the incidence of thrombosis, according to a study presented at the 2019 ASH Annual Meeting.

DOACs, such as apixaban, dabigatran, edoxaban and rivaroxaban, may be used in the treatment and secondary prevention of VTE, as well as for the prevention of stroke in the NVAF setting, explained lead investigator Jordan K. Schaefer, MD, Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Dexter, and colleagues.

“Current data, largely from patients treated with warfarin and aspirin, suggest that the addition of aspirin may increase bleeding risk without reducing thrombotic events,” they continued, noting that it is uncertain whether this applies to patients receiving DOACs with aspirin seeing as this patient population was not well represented in past clinical trials.

Thus, Dr Schaefer and colleagues to evaluate the impact of adding aspirin to DOAC for patients without an apparent need for combination therapy.

The study included adults receiving DOAC therapy for nonvalvular atrial fibrillation or VTE and included 2 propensity-matched cohorts based on aspirin use at the time of study enrollment (ie, DOACs vs DOAC plus aspirin). Patients were excluded if they had a history of heart valve replacement, recent myocardial infarction, or <3 months of follow-up.

The primary end point of the study was any new bleeding event, and secondary end points included new incidences of arterial or VTE, bleeding event type (eg, fatal, life threatening, major, clinically relevant non-major, intracranial or intraspinal), and death.

The study cohort included 2045 patients. Of these patients, 647 (31.6%) without a clear indication for aspirin received aspirin along with DOAC therapy and were compared with 639 matched patients.

After an average of 15.2 months’ follow-up, patients receiving DOAC plus aspirin had 319 bleeding events (0.33 bleeds per patient) compared with 261 bleeding events (0.41 bleeds per patient) in those receiving DOAC therapy alone (P = .02). Dr Schaefer and colleagues noted that this difference was largely driven by nonmajor bleeding events (151 with DOAC plus aspirin vs 109 with DOAC alone; P = .01).

A total of 2 fatal bleeding events were reported with DOAC monotherapy; the most common bleeding sites were cutaneous, gastrointestinal, and genitourinary. Similar rates of thrombosis were observed between the 2 treatment arms (19 events with DOAC plus aspirin vs 18 events with DOAC alone).

Additionally, Dr Schaefer and colleagues noted that patients who received aspirin in combination with DOAC therapy had more emergency department visits and hospitalizations than those given DOACs alone, but these differences were not statistically significant.

Patients receiving DOACs for VTE or NVAF and without a clear need for aspirin had more bleeding events with the addition of aspirin to their treatment regimen than did those given DOAC alone, without an apparent improvement in the incidence of thrombosis, Dr Schaefer and colleagues reported.

“Further study is needed to assess if DOAC plus aspirin is safer than warfarin plus aspirin, to compare the outcomes of the individual DOACs, and to confirm these findings in a larger cohort. Until such assessment is complete, clinicians should carefully consider the need to add aspirin in patients on DOAC therapy,” they concluded.—Janelle Bradley

Schaefer J, Li Y, Kong X, et al. Impact of Adding Aspirin to Direct Oral Anticoagulant Therapy without an Apparent Indication. Presented at: the 2019 ASH Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 787.