Prediabetes and Risk of Recurrent Ischemic Stroke in Atrial Fibrillation: A Propensity-Matched Cohort Study

Background The association between baseline prediabetes and recurrent ischemic stroke in patients with atrial fibrillation (AF) and prior cerebrovascular events remains uncertain. Methods Using the TriNetX United States Collaborative Network (67 healthcare organizations), adults with AF and prior ischemic stroke or transient ischemic attack were classified at baseline as having prediabetes or normoglycemia; diabetes mellitus was excluded. One-to-one propensity score matching balanced demographics and comorbidities. Cumulative risk and time-to-event analyses assessed recurrent ischemic stroke, all-cause mortality, gastrointestinal bleeding, and intracranial hemorrhage. Glycemic status was not updated during follow-up. Results After matching, 80,335 patients per cohort were analyzed (mean age 70 years; 54.7% male; all standardized mean differences <0.02). Cumulative recurrent stroke risk did not differ significantly (60.0% vs 60.4%; risk ratio 0.993, 95% confidence interval [CI] 0.982–1.005; P = 0.264). Time-to-recurrence was longer in the prediabetes cohort (median 1,794 vs 1,695 days; hazard ratio [HR] 0.960, 95% CI 0.943–0.978; P < 0.001). Prediabetes was associated with lower mortality (HR 0.891, 95% CI 0.873–0.910; P < 0.001) and gastrointestinal bleeding (HR 0.918, 95% CI 0.889–0.947; P = 0.003). Intracranial hemorrhage did not differ significantly (HR 0.961, 95% CI 0.917–1.007; P = 0.065). Conclusions Baseline prediabetes was not associated with increased cumulative recurrent stroke risk in this AF population. The observed time-to-event and secondary-outcome associations do not establish a protective effect. Metabolic surveillance remains an untested hypothesis; unmeasured care differences, residual confounding, and unaccounted-for glycemic progression limit interpretation and require prospective evaluation.