Key result
NOACs reduced all-cause mortality compared to control (4.4% vs 5.6%; RR 0.93; 95% CI 0.87-1.00; P=0.04) in patients with or at risk for CAD or PAD, but increased the risk of major bleeding.
Why the study?
While NOACs reduce cardiovascular events and increase moderate bleeding in patients with or at risk for CAD or PAD, their effect on survival was unknown.
Do NOACs reduce all-cause mortality in patients with or at risk for CAD or PAD?
Meta-Analysis (n=66,665)
Do NOACs reduce all-cause mortality in patients with or at risk for CAD or PAD?
In patients with or at risk for CAD or PAD, NOACs reduce all-cause mortality but increase the risk of major bleeding compared to control treatments.
NOACs merit consideration in CAD/PAD despite bleeding risk; extends meta-analytic support for antithrombotics in atherosclerosis.
INTRODUCTION: Several high quality randomized controlled studies were recently published on non-vitamin K oral anticoagulants (NOACs) in patients with or at risk for coronary artery (CAD) or peripheral artery disease (PAD). While a reduction on cardiovascular event is known and an increase in moderate bleeding is expected, the effect of this strategy on survival is currently unknown. Accordingly, we performed a comprehensive systematic review and meta-analysis of randomized controlled trials to investigate the effect of NOAC on survival. EVIDENCE ACQUISITION: We searched Pubmed, EMBASE, Cochrane Central Register, and Clinicaltrials.gov (last updated March 31st 2019). The primary endpoint was all-cause mortality at the longest reported follow-up. Coprimary endpoint was major bleeding according to the International Society on Thrombosis and Hemostasis (ISTH) criterion. EVIDENCE SYNTHESIS: We included ten randomized controlled trials comparing NOACs versus control treatment (placebo, single platelet or dual antiplatelet therapy) enrolling 66665 patients with or at risk for CAD or PAD. NOACs were associated with a decreased risk of mortality (825/41655 [4.4%] versus 405/25010 [5.6%] RR 0.93 [95% CI: 0.87-1.00], P=0.04), and an increased risk for major bleeding (RR 1.62 [95% CI: 1.23-2.13], P=0.0005) when compared to control. Findings were robust to trial sequential, subgroup, and sensitivity analyses. Low doses NOACs were associated with a reduced mortality when compared to standard dose NOACs. CONCLUSIONS: NOACs reduced all-cause mortality in patients with or at risk for CAD or PAD, even though they increased the risk of major bleeding. Future studies regarding the best doses of NOACs are warranted.
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Nagy et al. (2019) conducted a meta-analysis in Coronary artery disease (CAD) or peripheral artery disease (PAD) (n=66,665). Non-vitamin K oral anticoagulants (NOACs) vs. Placebo, single platelet or dual antiplatelet therapy was evaluated on All-cause mortality at the longest reported follow-up (RR 0.93, 95% CI 0.87-1.00, p=0.04). NOACs reduced all-cause mortality compared to control (4.4% vs 5.6%; RR 0.93; 95% CI 0.87-1.00; P=0.04) in patients with or at risk for CAD or PAD, but increased the risk of major bleeding.
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