Trimetazidine Is Associated With Ameliorated Stroke Risk in Patients With Both Ischemic Heart Disease and Atrial Fibrillation.

Background: Myocardial ischemia is closely associated with arrhythmogenesis and prognostication in patients with atrial fibrillation (AF). Trimetazidine ameliorates myocardial ischemia through prioritizing cardiomyocyte metabolism to glucose oxidation. Whether trimetazidine clinically reduces stroke risk in patients with ischemic heart disease and AF was unknown.

Methods: We recruited patients with ischemic heart disease from the Hong Kong Clinical Data Analysis and Reporting System between January 1, 1999 and December 31, 2020. Patients with comorbid AF were identified, and those with a history of prior stroke were excluded. Trimetazidine users and nonusers (with long-acting nitrates as the control) were compared for the primary end point of incident ischemic stroke using Cox proportional regression, with and without propensity matching.

Results: The primary analysis included 12 527 patients with ischemic heart disease and preexisting AF (mean age, 77.5±10.3 years; 44.6% men), who were further categorized as trimetazidine users (n=960) versus nonusers (n=11 567). Over a follow-up period of 1133 (interquartile range, 442-2454) days, 2160 patients (17.2%) developed new-onset ischemic stroke. Trimetazidine use was independently associated with a lower risk of new-onset ischemic stroke (hazard ratio [HR], 0.55 [95% CI, 0.44-0.68]; P<0.001). Propensity score-matched analyses revealed similar findings (adjusted HR, 0.65 [95% CI, 0.52-0.80]; P<0.001). Furthermore, trimetazidine was also independently associated with a lower risk of recurrent ischemic stroke (HR, 0.51 [95% CI, 0.37-0.69]; P<0.001).

Conclusions: Treatment with trimetazidine is associated with a lower risk of incident and recurrent stroke in patients with both ischemic heart disease and AF. These findings will need to be confirmed in randomized controlled trials.