The Safety of Aspirin Vs. Direct Oral Anticoagulants: A Meta-Analysis of Currently Published Clinical Trials

Introduction:

Several prior analyses have suggested that the use of warfarin leads to no observable difference in bleeding events when compared to aspirin. Although direct oral anticoagulants (DOACs) have been shown to be consistently safer than warfarin, data comparing the safety and efficacy of DOACs vs. aspirin has been sparse until recently. To date, two large randomized trials, EINSTEIN CHOICE and AVERROES, have compared DOACs to aspirin for secondary VTE prevention and prevention of thrombotic events in patents with atrial fibrillation respectively. Although DOACs were proven more effective then aspirin for both indications, the comparative bleeding risk between the two interventions remained unclear. In order to evaluate the safety of aspirin vs. DOACs we performed a meta-analysis of patients receiving aspirin vs. full dose DOAC within the two aforementioned trials.

Methods:

Using data from two recently-published, phase III trials-- EINSTEIN CHOICE and AVERROES-- we performed a meta-analysis using a Mantel-Haenszel random-effects model. Odds Ratios (OR) were generated along with forest plots. All analysis was performed with Review Manager (version 5.3 The Nordic Cochrane Centre, The Cochrane Collaboration, 2014).

Results:

In total, 3854 patients were treated with a therapeutic dose DOAC (apixaban 5mg BID or rivaroxaban 20mg daily) and 3876 were treated with varied doses of aspirin (81mg [46.9%], 100mg [27.6%], 162mg [18.5%], 243mg [1.9%], 324mg [5.0%], and unknown dose [0.2%]). Our analysis detected no statistically significant difference in major bleeding events (1.27% vs. 1.07%; p=0.4) or clinically-relevant, non-major bleeding events (3.22% vs. 2.65%; p=0.14) between the two groups (Table 1).

Conclusion:

This analysis suggests that aspirin is not appreciably safer than full dose DOACs in terms of bleeding risk. Given the size of this analysis, if a true difference in bleeding risk does exist, it is likely small and not clinically relevant. In addition to being significantly less effective, these results contradict any notion that aspirin is a safer alternative in terms of bleeding risk. Therefore, given the superior efficacy of DOACs for secondary VTE prevention and stroke prevention in atrial fibrillation, DOACs should always be preferentially used over aspirin in these populations. Future guidelines for clinical practice should reflect the evidence that aspirin is neither safer nor more effective for either indication.

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