Non-vitamin-K-antagonist oral anticoagulants (NOACs) after acute myocardial infarction: a network meta-analysis

Abstract

Abstract Background Balancing the risk of bleeding and thrombosis after acute myocardial infarction (AMI) is challenging and the optimal antithrombotic therapy remains uncertain. The potential of NOACs to prevent ischaemic cardiovascular events is promising but evidence remains limited. Purpose To assess the efficacy and safety of NOACs in addition to background antiplatelet therapy for secondary prevention post-AMI in people without an indication for anticoagulation. Methods We performed a systematic literature search in September 2022, assessed each included RCT, extracted study data and conducted a network meta-analyses (NMA) using the R package 'netmeta'. Results We included six RCTs, with 33,039 participants. Moderate to high-certainty-evidence suggests rivaroxaban reduces all-cause mortality (RR 0.82, 95% CI 0.69 to 0.98) and probably reduces cardiovascular death (RR 0.83, 95% CI 0.69 to 1.01). Low-certainty-evidence suggests dabigatran may reduce all-cause mortality compared with placebo (RR 0.57, 95% CI 0.31 to 1.06). There is probably little or no difference in all-cause mortality (RR 1.09, 95% CI 0.88 to 1.35) and cardiovascular death (RR 0.99, 95% CI 0.77 to 1.27) between apixaban and placebo. There is uncertainty about the rate of cardiovascular death with dabigatran compared with placebo, as the point estimate might suggest benefit (RR 0.72, 95% CI 0.34 to 1.52). Moderate to high-certainty-evidence suggests that NOACs (specifically apixaban and rivaroxaban) probably increase major bleeding compared with placebo (apixaban vs placebo: RR 2.41, 95% CI 1.44 to 4.06, rivaroxaban vs placebo: RR 3.31, 95% CI 1.12 to 9.77). The evidence is uncertain about the risk of major bleeding with dabigatran (dabigatran vs placebo: RR 1.74, 95% CI 0.22 to 14.12). The results from the NMA were inconclusive between the different NOACs in all individual doses for all primary outcomes. However, low-certainty-evidence suggests that apixaban (combined dose) might not be as effective as rivaroxaban or dabigatran in preventing all-cause mortality after AMI in people without an indication for anticoagulation. Conclusions Moderate to high-certainty-evidence suggests rivaroxaban reduces all-cause mortality and probably reduces cardiovascular death after AMI. Low-certainty evidence suggests dabigatran may reduce all-cause mortality. Moderate-certainty evidence suggests no meaningful difference in the rate of all-cause mortality and cardiovascular death between apixaban and placebo. Moreover, no meaningful benefit in efficacy outcomes was detected for specific therapy doses for any of the NOACs following AMI in people without an indication for anticoagulation. Moderate to high-certainty evidence suggests that NOACs probably increase major bleeding compared with placebo. Our network meta-analysis did not show superiority of one NOAC over another for any primary outcome. Head-to-head trials, comparing NOACs against each other, are required to provide more certain evidence.