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Study Summary

Angina might persist or reoccur despite successful revascularization with percutaneous coronary intervention (PCI) and antianginal therapy. The ATPCI study was an international, randomized, double-blind, placebo-controlled, event-driven trial that investigated the effect of trimetazidine — an antianginal agent that improves the metabolism of the ischemic myocardium through the enhanced production of ATP — added to standard background medical therapy in patients with coronary artery disease who underwent successful PCI <30 days before randomization. Patients (N = 6,007) were included regardless of the presence or absence of angina symptoms after the index PCI. At a median follow-up of 47.5 months, no significant difference in the primary composite end point (cardiac death, rehospitalization for a cardiac event, recurrence or persistence of angina requiring modification of the antianginal regimen or recurrence or persistence of angina requiring coronary angiography) was observed between patients who received trimetazidine (modified-release 35 mg twice daily) and those who received placebo (23.3% versus 23.7%; HR 0.98; 95% CI 0.88-1.09; P = 0·73; see accompanying Hurst's Central Illustration), a finding observed across multiple subgroups. Individual components of the primary efficacy end point also did not differ significantly. No drug-related adverse safety end points were observed during the study.

Commentary

Study Strengths: This was a large, international, multicenter, placebo-controlled trial with few exclusion criteria, which enhances the external validity of the study. Patients enrolled in the study were receiving appropriate guideline-recommended therapy for cardiovascular disease. Follow-up time was relatively long (∼4 years) and ∼96% of patients completed the follow-up.

Study Limitations: Although the investigators were able to enroll the target patient population of at least 5800 patients, the event rates were lower than expected from the original power calculations, probably due to the inclusion of younger patients with a low atherosclerotic burden (about half of the patients had single-vessel disease), improvement of PCI technologies over time, and high adherence to and use of contemporary guideline-directed medical therapy. The proportion of patients with CCS class 2 or higher angina decreased throughout the study in both the trimetazidine and placebo groups, and the recurrence of significant angina was uncommon in the study, with no significant differences between groups. The investigators only included patients who had undergone successful PCI, so whether trimetazidine could have been effective in patients who had failed PCI or had incomplete revascularization remains unknown.

Next Steps/Clinical Perspective: Trimetazidine failed to reduce the risk of adverse cardiac events compared with placebo after successful PCI. Similar results were obtained with ranolazine in the RIVER-PCI study. While the lower-than-expected event rates may have contributed to the null findings, it is likely that the prophylactic use of trimetazidine added to guideline-directed medical therapy does not improve clinical outcomes after PCI. However, it could still have a role to control symptoms in patients with refractory angina on maximally-tolerated medical therapy and/or coronary anatomy not amenable to revascularization.

Trial Reference

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Ferrari  R, Ford  I, Fox  K,  et al. Efficacy and safety of trimetazidine after percutaneous coronary intervention (ATPCI): a randomised, double-blind, placebo-controlled trial. Lancet. doi:10.1016/S0140-6736(20)31790-6.

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