Cardiovascular outcomes with SGLT-2 inhibitors in individuals with diabetes and co-existing atrial fibrillation: A systematic review and meta-analysis

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease and atrial fibrillation. Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) have demonstrated benefit in reducing T2DM-related morbidity and mortality, but their effects in individuals with concomitant T2DM and atrial fibrillation remain unclear. This meta-analysis is the first to evaluate impact of SGLT-2i in this patient population. METHODS: PubMed/MEDLINE, Cochrane Library, and reference lists of the included articles were systematically searched. Results were pooled using a random-effects model and outcomes were reported as risk ratios (RR) with 95 % confidence intervals (CIs). Meta-regression analyses based on baseline patient characteristics were conducted to assess potential sources of heterogeneity. RESULTS: Seven retrospective cohort studies and one randomized controlled trial corresponding to 37,229 patients were included, of whom 13,030 received SGLT-2i and 24,199 received other oral anti-diabetic drugs. Follow-up ranged from 2 to 5 years. SGLT-2i use was associated with decreased risk of all-cause mortality (RR = 0.37; 95 % CI: 0.28-0.50), heart failure (RR = 0.66; 95 % CI: 0.53-0.83), stroke (RR = 0.76; 95 % CI: 0.66-0.88), and cardiovascular mortality (RR = 0.57; 95 % CI: 0.44-0.74). No significant difference was observed for myocardial infarction (RR = 0.94; 95 % CI: 0.78-1.12). Results were largely consistent across shorter (<3 years) and longer (≥3 years) follow-up durations. Meta-regression demonstrated no significant associations with baseline patient characteristics (age, gender, prior MI, or prior stroke). CONCLUSION: SGLT-2i reduced all-cause mortality, heart failure, stroke, and cardiovascular mortality in individuals with T2DM and atrial fibrillation. Large-scale, randomized controlled trials are warranted to confirm these findings.