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Trimetazidine Is Associated With Ameliorated Stroke Risk in Patients With Both Ischemic Heart Disease and Atrial
Yuen-Ting Cheng1, Gregory Y H Lip2,3, Bernard M Y Cheung1
1Department of Medicine, School of Clinical Medicine The University of Hong Kong Hong Kong SAR China.
Insights
Trimetazidine use in patients with atrial fibrillation and ischemic heart disease significantly lowers the risk of new and recurrent strokes. This finding suggests a potential therapeutic benefit for stroke prevention in this high-risk population.
Area of Science:
- Cardiology
- Metabolic Cardiology
- Neurology
Background:
- Myocardial ischemia is a known risk factor for stroke in atrial fibrillation (AF) patients.
- Trimetazidine optimizes cardiomyocyte metabolism, prioritizing glucose oxidation to alleviate myocardial ischemia.
- The clinical impact of trimetazidine on stroke risk in patients with concurrent ischemic heart disease and AF remains under investigation.
Purpose of the Study:
- To investigate the association between trimetazidine use and the risk of incident ischemic stroke in patients with ischemic heart disease and AF.
- To evaluate the effect of trimetazidine on recurrent ischemic stroke in the same patient cohort.
Main Methods:
- A retrospective cohort study was conducted using data from January 1, 1999, to December 31, 2020.
- Patients with ischemic heart disease and AF, excluding those with prior stroke, were analyzed.
- Cox proportional regression models, with and without propensity score matching, compared trimetazidine users to nonusers (long-acting nitrates).
Main Results:
- The study included 12,527 patients (mean age 77.5 years; 44.6% male).
- Trimetazidine use was independently associated with a reduced risk of new-onset ischemic stroke (HR 0.55; P<0.001) and recurrent ischemic stroke (HR 0.51; P<0.001).
- Propensity score matching confirmed these findings, showing a reduced risk of incident stroke with trimetazidine (aHR 0.65; P<0.001).
Conclusions:
- Trimetazidine treatment is linked to a lower incidence of both new and recurrent strokes in patients with coexisting ischemic heart disease and AF.
- These observational findings highlight trimetazidine as a potential agent for stroke risk reduction in this population.
- Further validation through randomized controlled trials is warranted to confirm these results.
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.
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