Patients with diabetes mellitus and atrial fibrillation treated with NOACs: Meta-analysis of 8 outcomes in 58, 634 patients across 4 randomized controlled trials.

AIMS Concomitant atrial fibrillation (AF) and diabetes mellitus (DM) increases risk of stroke and systemic embolic events. This meta-analysis assessed the benefit/risk balance of non-vitamin K antagonist oral anticoagulants (NOACs) vs warfarin, and explored whether there was effect modification by DM or heterogeneity in outcomes between NOACs in patients with and without DM. METHODS We performed a meta-analysis of 58,634 patients from four phase 3 trials of NOAC vs warfarin in patients with AF, comparing the primary outcomes of efficacy and safety and 6 other secondary outcomes in patients stratified by the presence of DM. Interaction testing was used to assess for heterogeneity of treatment effects. A meta-regression was performed to evaluate the influence of baseline characteristics. RESULTS NOACs reduced the risk of stroke/SEE in 18,134 patients with DM [hazard ratio (HR) 0.80; 95% confidence interval (CI) (0.69-0.93), I2 3.90] to a similar degree as in 40,500 patients without DM [HR 0.82; 95% CI (0.74-0.91)], I2 16.33 p-int 0.81). There was no effect modification of DM on the relative reduction with NOACs vs warfarin in major bleeding (DM : 0.95, 95% CI 0.75-1.20, I2 43.83; no DM: 0.83, 95% CI 0.55-1.24; I2 87.90; p-int 0.37). Intracranial Haemorrhage (HRs 0.51 and 0.47, p-int 0.70) and cardiovascular death (HRs 0.87 and 0.90, p-int 0.70) were significantly reduced by NOACs in the presence or absence of DM. CONCLUSION NOACs are more effective and safer than warfarin in AF patients with or without DM and absent contraindications, NOACs should be the anticoagulation treatment choice in diabetics.

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