Effects of GLP ‐1 receptor agonists on incidence and outcomes of ischemic stroke and myocardial infarction: A systematic review and meta‐analysis

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) demonstrate cardiovascular benefits beyond glycemic control, but the benefits of protection across cerebrovascular and cardiovascular territories remain incompletely studied in the literature. We aim to evaluate whether GLP-1 RAs provide balanced protection against stroke and myocardial infarction (MI) and identify factors that modify this protection. METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials comparing GLP-1 RAs with placebo that reported cerebrovascular and cardiovascular outcomes. We calculated hazard ratios (HRs) for stroke and MI and developed a novel Territorial Benefit Ratio (TBR = HR stroke/HR MI) to quantify relative cerebrovascular versus coronary protection. Meta-regression analyses identified factors modifying territorial protection. RESULTS: Eleven trials with 85 373 participants met inclusion criteria. GLP-1 RAs significantly reduced stroke (HR 0.88, 95% CI 0.80-0.96) and MI (HR 0.87, 95% CI 0.79-0.97), resulting in an overall balanced TBR of 1.01 (95% CI 0.89-1.15). Protection patterns varied significantly by patient subgroups: prior stroke history provided better stroke protection (HR 0.73, NNT 54), while prior MI history provided better MI protection (HR 0.79, NNT 55). MI protection emerged earlier within the first six months (HR 0.81), while stroke protection strengthened over time (over 24 months: HR 0.80). Renal dysfunction, atrial fibrillation, and hypertension shifted protection towards stroke, while dyslipidemia provided better MI protection. CONCLUSIONS: GLP-1 RAs demonstrate a protection-in-territory-at-risk pattern with important temporal findings and results translated. These findings support a personalised approach to GLP-1 RA therapy that considers patients' vascular history and risk profiles. The earlier emergence of MI protection and later strengthening of stroke protection deliver significant highlights for clinical expectations and treatment persistence.