Angina may persist or recur despite successful revascularization with percutaneous coronary intervention. In these cases, antianginal treatment is supplemented. To demonstrate the effectiveness of this approach, a clinical trial was conducted to demonstrate the long-term potential benefit and safety of trimetazidine as add-on therapy. But it didn’t.
Patients who undergo successful percutaneous coronary intervention (PCI) for angina and non-ST-segment elevation acute coronary syndrome usually have good long-term outcomes with optimal medical therapy. However, recurrence of angina symptoms or cardiovascular events may still occur. This should prevent the additional administration of antianginal drugs. This procedure has so far been given a Class IIA recommendation in the European guidelines. Trimetazidine is an antianginal agent that improves energy metabolism of ischemic myocardium and may improve outcomes and symptoms in patients who have recently had PCI. The substance inhibits beta-oxidation of fatty acids and enhances glucose oxidation, which in sum reduces myocardial oxygen consumption.
In a randomized, double-blind, placebo-controlled, event-driven trial, 6007 patients at 365 centers in 27 countries who had successfully undergone PCI were studied over five years. Patients were between 21 and 85 years of age and had had either elective PCI for stable angina or urgent PCI for unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI) less than 30 days before randomization. Randomized to receive either 35 mg trimetazidine or placebo twice daily.
The primary efficacy end point was a combination of cardiac death; hospitalization for a cardiac event; recurrence or persistence of angina requiring addition, change, or increase in dose of at least one antianginal drug; or recurrence or persistence of angina requiring coronary angiography.
Endpoint events very rare
The results show that there was no significant difference in incidence between the two groups. So, in the end, it didn’t matter whether the patients were treated with the active ingredient or placebo. The relative risk was 0.98 (95% CI 0.88-1.09; p=0.73) in the trimetazine group. This was true for patients who had received PCI for chronic angina as well as for patients after NSTEMI. In addition, endpoint events were quite rare at 25%. A look at the subgroups also revealed no differences. Patients in the verum arm did not have fewer symptoms, nor did they improve more frequently in angina classification by CCS. 1219 (40-9%) of 2983 patients in the trimetazidine group and 1230 (41-1%) of 2990 patients in the placebo group had serious treatment-related adverse events. However, long-term administration of trimetazidine was not associated with statistically significant safety concerns.
Results give pause for thought
It is difficult to fathom how the disappointing results came about. One possible reason could have been the already good treatment of those affected. Nearly all patients had received dual antiplatelet therapy and were taking statins. The use of other antianginal drugs was also the rule rather than the exception. 83% were taking beta blockers, 27% calcium channel blockers, 12% long-acting nitrates, and 22% other antianginal agents. Nevertheless, routine use of oral trimetazidine 35 mg twice daily for several years should be reconsidered. It does not appear to affect angina recurrence or outcome in patients receiving optimal medical therapy after successful PCI.
Further reading:
- Ferrari R, et al: Efficacy and safety of trimetazidine after percutaneous coronary intervention (ATPCI): a randomised, double-blind, placebo-controlled trial. Lancet 2020, August 30. DOI: 10.1016/S0140-6736(20)31790-6.
CARDIOVASC 2020; 19(4): 24 (published 8/12/20, ahead of print).
