Efficacy and Safety of the Use of Non-vitamin K Antagonist Oral Anticoagulants in Patients with Ischemic Heart Disease: A Meta-Analysis of Phase III Randomized Trials.

BACKGROUND: There are conflicting published data on non-vitamin K antagonist oral anticoagulants (NOACs), with varying evidence of benefit or harm in acute coronary syndrome (ACS) and non-ACS cohorts. To explore the efficacy and safety of NOAC use in patients with ischemic heart disease (IHD), we conducted a meta-analysis of phase III randomized controlled trials (RCTs).

METHODS: We systematically searched the Cochrane Library, PubMed, and Embase databases. A random-effect model was selected to pool the effect measurement estimates (hazard ratios [HRs] and 95% confidence intervals [CIs]).

RESULTS: Three RCTs with 39,492 enrolled IHD patients were included. Compared with placebo, NOACs were associated with reduced risks of major adverse cardiac events (MACE) (HR 0.83, 95% CI 0.76-0.90), cardiovascular death (HR 0.82, 95% CI 0.72-0.93), and myocardial infarction (HR 0.87, 95% CI 0.78-0.97) accompanied by increased risks of major bleeding (HR 2.46, 95% CI 1.42-4.26), but not fatal bleeding (HR 1.35, 95% CI 0.76-2.39) or intracranial hemorrhage (HR 2.19, 95% CI 0.91-5.27). Subgroup analysis revealed that NOACs were associated with an increased risk of major bleeding in patients who received dual antiplatelet therapy compared with patients who received single antiplatelet therapy (3.01, 1.82-4.98 vs. 1.66, 1.37-2.03; P for interaction 0.03) and patients with ACS compared with patients with non-ACS (3.27, 2.16-4.95 vs. 1.66, 1.36-2.02; P for interaction 0.004).

CONCLUSIONS: In patients with IHD, NOACs confer protection against thrombosis-related complications, but at the cost of an increased hazard of major bleeding. NOACs plus a single antiplatelet drug seem to be a good choice for patients with IHD.