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After successful percutaneous coronary intervention (PCI), prophylactic use of trimetazidine on top of optimal medical therapy offered no additional relief from chest pain nor reduction in cardiac risk, the ATPCI trial showed.

The antianginal drug was no better than placebo at reducing the combined endpoint of cardiac death, hospitalization for cardiac events, recurrent angina leading to adjustment in antianginal medication dosage, or recurrent angina requiring coronary angiography over a median 47.5 months (23.3% vs 23.7%, HR 0.98, 95% CI 0.88-1.09).

Individual endpoints of the primary endpoint favored neither trimetazidine nor placebo. Trimetazidine appeared to have no effect across prespecified subgroups, including patients undergoing elective or urgent PCI, according to Roberto Ferrari, MD, of University of Ferrara and Ospedale di Cona in Italy.

A self-described "rather disappointed" Ferrari presented ATPCI at the European Society of Cardiology (ESC) virtual meeting. The findings were simultaneously published online in the .

The failure of trimetazidine may have to do with the fact that recurrent angina was less common than predicted in the study. Investigators had opted to extend follow-up by 12 months given lower-than-expected event rates.

"Much of this might be explained by the high routine use of antianginal medications after PCI. These medications might have been prescribed for reasons other than angina, such as blood pressure control, and therefore might have contributed to the absence of benefit seen with trimetazidine," the investigators said. They added that patients could have had ischemia improve over time or figured out how not to provoke their angina.

"In the specific ATPCI population, combining successful PCI with optimal preventive and antianginal therapy was probably sufficient for symptom control in most cases," according to Ferrari and colleagues.

Another explanation for trimetazidine's failure could be that PCI patients were enrolled regardless of angina status. "What might have been interesting would be to see the analysis subgrouped by angina status at the beginning of the trial," offered Tracy Wang, MD, MHS, of Duke Clinical Research Institute in Durham, North Carolina.

For now, treatment of patients with recurrent chest pain after PCI remains an unmet need, she said, citing showing that 29% of patients undergoing PCI for acute MI had persistent chest pain 6 weeks after the procedure -- a third of whom still had lingering symptoms at 1 year.

Ranolazine (Ranexa) is another antianginal drug that has at improving outcomes after PCI.

Ferrari's group said they had selected trimetazidine for the present study as it is thought to be "particularly effective" in managing microvascular dysfunction, which some believe plays an important role in the pathophysiology of angina after PCI. Trimetazidine is a unique antianginal medication that works by improving the metabolism of ischemic myocardium, not reducing heart rate or blood pressure.

"One often wonders if this should be in the optimal medical therapy regimen of a trial in patients with moderate to severe ischemia before revascularization to improve angina and outcomes. Post-revascularization, there does not seem to be a benefit for these types of drugs," according to Roxana Mehran, MD, of Mount Sinai School of Medicine in New York City.

The included 6,007 adults (mean age 60.9; 77.0% men) who had received PCI (elective for stable angina or urgent for unstable angina or non-ST segment elevation MI).

Participants were randomized within the first 30 days following revascularization to oral trimetazidine 35 mg twice daily or placebo.

Throughout the trial, they remained on background optimal medical therapy, including the 1.3 antianginal agents per person at baseline.

No trimetazidine-related safety issues were reported.

Ferrari cautioned that his group only tested one dose of trimetazidine. Previous studies showed higher doses to be more promising, he said during an ESC press conference.

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