Does the presence of diabetes mellitus confer an increased risk of stroke in patients with atrial fibrillation on direct oral anticoagulants? A systematic review and meta-analysis

Background and aims: There is limited data on clinical outcomes in high risk groups such as patients with diabetes mellitus (DM) with atrial fibrillation (AF) on direct-acting oral anticoagulants (DOACs). Using a systematic review and meta-analysis of published studies, we aimed to determine the risk of stroke and other clinical outcomes in patients with AF on DOACs, with or without DM. Methods: Observational cohort studies reporting clinical outcomes in patients with AF on DOACs, with or without DM were identified from MEDLINE, Embase, Web of Science, the Cochrane Library, and search of bibliographies to April 2020. Summary measures of effect were relative risks with 95% confidence intervals (CIs). Results: Eight studies comprising of 4 observational cohorts (n = 76,260 participants) and 4 randomised controlled trials (RCTs) (n = 71,683 participants) were included. In RCTs, DOACs compared with warfarin reduced the risk of the composite outcome of stroke and systemic embolism, CVD death and intracranial bleeding in patients with DM: RRs (95% CIs) of 0.75 (0.62-0.90), 0.84 (0.72-0.97), and 0.57 (0.40-0.81) respectively. The corresponding estimates for patients without DM were 0.81 (0.68-0.96), 0.93 (0.80 -1.08), and 0.47 (0.31-0.70) respectively. There was no evidence of interactions between DM status and effects of DOACs. The absolute reduction in clinical outcomes with DOACs compared to warfarin was greater in DM than without DM. Regardless of treatment strategy, interventional and observational evidence indicate that patients with DM had higher rates of stroke or systemic embolism, mortality and major bleeding compared to patients without DM. Conclusions: Patients with AF and DM have increased risk of vascular events, which is reduced with the use of DOACs. The use of DOACs should be considered as an option in reducing the risk of stroke in these populations. (C) 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.