Trimetazidine lowers risk of stroke in presence of both IHD and AF

Treatment with the antianginal agent trimetazidine appears to protect against the incidence of stroke and its recurrence in patients with both ischaemic heart disease (IHD) and atrial fibrillation (AF), as shown in a study from Hong Kong.

Compared with nonuse, trimetazidine use was associated with a more than 40-percent reduction in the risk of new‐onset ischaemic stroke (9.9 percent vs 17.9 percent; number needed to treat [NNT] 13; hazard ratio [HR], 0.55, 95 percent confidence interval [CI], 0.44–0.68; p<0.001) and any stroke (12.7 percent vs 24.3 percent; NNT 9; HR, 0.51, 95 percent CI, 0.42–0.62; p<0.001). [J Am Heart Assoc 2025;doi:10.1161/JAHA.125.041629]

Among patients who had a history of prior stroke, trimetazidine use also lowered the risk of recurrence of both ischaemic stroke (HR, 0.51, 95 percent CI, 0.37–0.69; p<0.001) and any stroke (HR, 0.53, 95 percent CI, 0.45–0.64; p<0.001).

Propensity score–adjusted multivariate analyses yielded similar results.

“Altogether, these findings may potentially provide a new therapeutic avenue for stroke prevention in ischemia‐related AF,” the authors said.

Trimetazidine may reduce AF burden and thereby risk of stroke by relieving atrial myocardial ischaemia, given that AF burden is positively related to stroke, they explained. Other than its anti-ischaemic effect, the drug may also stabilize the heart’s electrical signals and provide general cardiovascular protection. [JAMA Cardiol 2018;3:601-608; Pacing Clin Electrophysiol 2009;32:239-244; Eur Heart J 2007;28:1102-1108; Cardiovasc Res 2010;88:150-158; Heart 2011;97:1495-1500]

The authors called for additional randomized controlled trials and mechanistic studies are needed to confirm the findings and establish the underlying mechanisms.

Currently, trimetazidine is recommended as a second-line therapy in the 2019 European Society of Cardiology guidelines for the relief of symptomatic angina. Unlike other antianginal drugs, trimetazidine exerts no hemodynamic effect, making it a favourable option for patients who cannot tolerate medications with negative inotropic or bradycardic effects, as the authors pointed out. [Eur Heart J 2020;41:407-477; Int J Cardiol 2019;293:39-44]

However, the drug is not licensed in the US and the UK. In 2012, the European Medicines Agency restricted its use due to a potential link with Parkinsonian symptoms. Then again, postmarketing surveillance data suggested this risk was very low, approximately 0.36 cases per 100,000 person-years, with those symptoms typically resolving within 4 months of stopping the drug. [European Medicines Agency 2012;EMA/CHMP/417861/2012; Eur Heart J Cardiovasc Pharmacother 2016;2:266-272]

The authors emphasized that the growing body of evidence suggesting that trimetazidine has potential benefits for cardiovascular diseases beyond angina warrant reassessment of the drug’s clinical value and role in the future.

For the study, the authors recruited 12,527 patients with IHD and pre-existing AF (mean age 77.5 years, 44.6 percent male) from the Hong Kong Clinical Data Analysis and Reporting System. Of the patients, 960 were trimetazidine users and 11,567 were nonusers. Over a median follow‐up of 1,133 days, 2,160 patients (17.2 percent) developed new‐onset ischaemic stroke.

Subgroup analysis showed no interaction between trimetazidine and anticoagulant use (p=0.53), with trimetazidine therapy being associated with a reduced risk of incident ischaemic stroke risk among both anticoagulant users (HR, 0.72, 95 percent CI, 0.56–0.92; p=0.01) and nonusers (HR, 0.49, 95 percent CI, 0.34–0.70; p<0.001).