Factor Xa inhibitors versus warfarin in patients with non-valvular atrial fibrillation and diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

ABSTRACT

Background: Patients with non-valvular atrial fibrillation with diabetes face increased stroke and cardiovascular risks. This study compares factor Xa inhibitors and warfarin using data from randomized controlled trials (RCTs). Methods: MEDLINE, Embase, and Cochrane CENTRAL databases were searched for RCTs comparing the risk of efficacy and safety of any factor Xa inhibitors with dose-adjusted warfarin by diabetes status. Incidence of stroke/systemic embolism, major bleeding, intracranial hemorrhage, ischemic stroke, all-cause mortality, risk of hemorrhagic stroke, and myocardial infarction were among the outcomes of interest. A generic inverse-weighted random-effects model was used to calculate hazard ratios (HRs) with 95 percent confidence intervals (CIs). Results: After applying exclusion criteria, four RCTs containing 19 818 patients were included in the analysis. Compared with warfarin, meta-analysis showed statistically significant reduction in incidence of stroke/systemic embolism (HR 0.80 [95% CI 0.69-0.92]; P=0.002), intracranial hemorrhage (HR 0.49 [95% CI 0.37-0.65]; P<0.001), and risk of hemorrhagic stroke (HR 0.37 [95% CI 0.20-0.66]; P=0.001) in patients on factor Xa inhibitors. However, there was no discernible difference between two treatment arms in incidence of major bleeding (HR 0.93 [95% CI 0.84-1.04]; P=0.19), ischemic stroke (risk ratio (RR) 0.90 [95% CI 0.73-1.12; P=0.34), myocardial infarction (RR 0.88 [95% CI 0.67-1.15]; P=0.35), and all-cause mortality (RR 0.89 [95% CI 0.79-1.01]; P=0.06). Conclusion: Factor Xa inhibitors show a favorable balance between efficacy and safety compared with warfarin, which is consistent across a wide range of patients with atrial fibrillation known to be at high risk for both ischemic and bleeding events.