Huang WY, et al. - Researchers conducted a systematic review and meta-analysis of randomized clinical trials for the comparison across all indications of intracranial hemorrhage with individual non–vitamin K antagonist oral anticoagulants (NOACs) vs aspirin. It was noted that a 15-mg to 20-mg dose of rivaroxaban once daily was related to substantially higher odds of intracranial hemorrhage than aspirin. On the other hand, a 5-mg dose of apixaban twice daily and a 10-mg dose of rivaroxaban once daily or a 5-mg dose twice daily were not correlated with increased risks. For administration of 15 to 20 mg of rivaroxaban once daily, only patients with atrial fibrillation should be considered.

Methods

• For this investigation, researchers searched PubMed, Embase, CENTRAL, and ClinicalTrials.gov from inception to May 28, 2018, with the terms novel oral anticoagulants, non–vitamin K antagonist oral anticoagulants, direct oral anticoagulants, dabigatran, rivaroxaban, apixaban, edoxaban, warfarin, Coumadin, vitamin K antagonist, aspirin, acetylsalicylic acid, or ASA, and major bleeding, fatal bleeding, or intracranial hemorrhage.
• Search was restricted to clinical trials on humans.
• No language restrictions in this analysis.
• Study selection included randomized clinical trials of 3 months or longer that included a comparison of the outcomes of NOAC use compared with use of aspirin.
• From eligible studies, 2 investigators independently abstracted data.
• Based on the Mantel-Haenszel method, they computed a fixed-effect estimate.
• Odds ratios (ORs) with 95% CI were utilized as a measure of the relationship of individual NOAC vs aspirin with the risk of intracranial hemorrhage.
• The hypothesis that intracranial hemorrhage risk would be higher with NOACs vs aspirin was formulated during data collection.

Results

• The principal analysis included 5 randomized clinical trials comparing 1 or more NOACs with aspirin, with 39,398 people selected.
• Pooling the outcomes from the fixed-effects model demonstrated that a dose of 15 to 20 mg of rivaroxaban once daily was related to an increased risk of intracranial hemorrhage (2 trials; OR, 3.31 [95% CI, 1.42 to 7.72]) compared with aspirin.
• On the other hand, a 10-mg dose of rivaroxaban once daily or a 5-mg dose twice daily (3 trials; OR, 1.43 [95% CI, 0.93 to 2.21]) and a 5-mg dose of apixaban twice daily (1 trial; OR, 0.84 [95% CI, 0.38 to 1.88]) were not.