Safety and efficacy of nonvitamin K antagonist oral anticoagulants versus warfarin in diabetic patients with atrial fibrillation: A study‐level meta‐analysis of phase III randomized trials

Abstract

In patients with atrial fibrillation (AF), the safety and efficacy of nonvitamin K antagonist oral anticoagulants (NOACs) vs warfarin according to diabetes mellitus (DM) status are not completely characterized. We performed a meta-analysis to clarify whether in these patients the strategy of oral anticoagulation should be tailored to diabetes status. In this study-level meta-analysis, we included 4 randomized phase III trials comparing NOACs and warfarin in patients with nonvalvular AF; a total of 18 134 patients with DM and 40 454 without DM were overall considered. Incidence of the following outcome measures was evaluated during the follow-up: stroke or systemic embolism, ischemic stroke, major bleeding, intracranial bleeding, and vascular death. Use of NOACs compared with warfarin reduced stroke/systemic embolism in diabetic (Risk Ratios [RR] 0.80, 95% CI 0.68-0.93; P = .004) and nondiabetic patients (RR 0.83, 0.73-0.93; P = .001) (P for interaction .72). No interaction between diabetes status and benefits of NOACs was found for the occurrence of ischemic stroke, major bleeding, or intracranial bleeding (P for interaction >.05 for each comparison). Reduction of vascular death rates with NOACs was significant in diabetic patients (4.97% vs 5.99% with warfarin; RR 0.83, 0.72-0.96; P = .01), in whom absolute the reduction of this outcome measure was higher than in nondiabetics (1.02% vs 0.27%), although no interaction was present (P = .23). Results of this meta-analysis support the safety and efficacy of NOACs compared with warfarin in diabetic patients with nonvalvular AF.

Novel oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and diabetes—Good or excellent?

“…Consistent results were observed in the meta‐analysis by Patti et al published in previous issue of Diabetes/Metabolism Research and Reviews , which engages specifically in diabetic patients from said 4 phase III trials. As expected, compared with patients without diabetes, patients with diabetes had higher rates of thromboembolic events and death.…”

Left atrial appendage occlusion for stroke prevention in diabetes mellitus patients with atrial fibrillation: Long‐term results

“…In addition, in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) study evaluating apixaban versus warfarin, diabetes was found to be a risk factor for major hemorrhage. 36 In contrast, in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) study, 8 the ROCKET-AF (Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation) study, 37 and in metaanalyses, 38,39 there was no correlation between patients with DM and an increased bleeding rate compared with the general population. It should be noted that there were no significant differences in antithrombotic treatment at the time of last follow-up between groups in the present study.…”

Use of non‐vitamin K oral anticoagulants in people with atrial fibrillation and diabetes mellitus

“…Regardless of the assigned anticoagulation treatment, participants with diabetes had an increased absolute and relative risk of stroke and vascular deaths , although it should be noted that the higher risk of cardiovascular events observed in people with diabetes mellitus was derived mainly from unadjusted comparisons.…”

“…Efficacy analyses were based on the intention‐to‐treat population. A study‐level meta‐analysis of the four trials has shown that the use of non‐vitamin K oral anticoagulants vs warfarin significantly reduced the composite efficacy endpoint both in participants with diabetes and in those without diabetes, with no significant interaction by diabetes status and treatment ( P value for interaction 0.72; Table ) . Moreover, as participants with diabetes were at increased absolute risk for the primary endpoint compared with those without diabetes, similar relative risk reduction across the diabetes mellitus population using non‐vitamin K oral anticoagulants translated into greater absolute benefit .…”

“…The primary safety outcome was defined as major bleeding by the International Society on Thrombosis and Haemostasis (ISTH) definition and safety analyses were generally based on the on‐treatment population. Overall, rates of major bleeding were higher in participants with diabetes vs those without diabetes (6.35% vs 5.40%, respectively; P < 0.0001) . Nevertheless, there are some differences between the trials with regard to drug safety (Table ).…”