Bleeding Risks With Non–Vitamin K Oral Anticoagulants Versus Single Antiplatelet Therapy

BACKGROUND: In several settings, therapeutic-dose non-vitamin K oral anticoagulants (NOACs) are superior to aspirin for the prevention of arterial and venous thromboembolism. PURPOSE: To estimate differences in bleeding risks between NOACs and single antiplatelet therapy. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to June 2024 without language restrictions. STUDY SELECTION: Randomized controlled trials (RCTs) comparing therapeutic-dose NOACs versus single antiplatelet therapy, with a minimum treatment duration of 3 months. DATA EXTRACTION: Data extraction was done independently and in duplicate. DATA SYNTHESIS: Nine RCTs with 26 224 participants were included. All studies used aspirin as antiplatelet therapy. Compared with aspirin, apixaban had similar rates of major bleeding (risk difference [RD], 0.0 percentage point [95% CI, -1.3 to 2.6 percentage points]; 5 trials) and intracranial hemorrhage (RD, -0.2 percentage point [CI, -0.6 to 1.4 percentage points]; 5 trials). Compared with aspirin, dabigatran had similar rates of major bleeding (RD, 0.5 percentage point [CI, -2.1 to 19.6 percentage points]; 2 trials) and intracranial hemorrhage (RD, 0.0 percentage point [CI, -1.1 to 24.5 percentage points]; 2 trials). Compared with aspirin, rivaroxaban had higher rates of major bleeding (RD, 0.9 percentage point [CI, -0.1 to 3.7 percentage points]; 2 trials) and intracranial hemorrhage (RD, 0.3 percentage point [CI, -0.1 to 79.7 percentage points]; 2 trials). The evidence certainty ranged from low to moderate. LIMITATION: Confidence intervals were wide and included the possibility of a null effect. CONCLUSION: In this systematic review of RCTs, rates of major bleeding for therapeutic-dose apixaban and dabigatran were similar to those for low-dose aspirin, whereas rates were higher for rivaroxaban. PRIMARY FUNDING SOURCE: None. (PROSPERO: CRD42024553683).