Trimetazidine does not improve angina, other outcomes after PCI
Click Here to Manage Email Alerts
In patients who underwent PCI, trimetazidine, a drug to improve myocardial metabolism, did not improve angina recurrence or other CV outcomes, according to results of the ATPCI trial presented at the European Society of Cardiology Congress.
Researchers evaluated long-term benefits and safety of trimetazidine after PCI for stable angina or non-STEMI in 6,007 patients who were on optimal medical therapy. After a median follow-up of 47.5 months after PCI, the primary endpoint of cardiac death, hospitalization for a cardiac event, or recurrence/persistence of angina requiring coronary angiography or change to antianginal drug regimen occurred in 23.3% of those assigned trimetazidine compared with 23.7% of those assigned placebo (HR = 0.98; 95% CI, 0.88-1.09).
There were no differences between the groups in any of the individual components of the primary endpoint, according to the researchers.
The data were simultaneously published in The Lancet.
“Previous investigations have shown that angina pectoris might reoccur despite successful PCI,” Roberto Ferrari, MD, PhD, FESC, professor of cardiology at the University of Ferrara, Italy, and past president of the ESC, said during a press conference. “There are no contemporary data on the prognostic benefit of anti-anginal drugs in post-PCI patients. Trimetazidine is the only anti-anginal drug which is devoid of hemodynamic effects. It acts by improving the metabolism of the ischemic myocardium. ATPCI tested the value of metabolic therapy with trimetazidine.”
There were no differences in the primary endpoint regardless of whether a patient underwent elective PCI (HR = 0.94; 95% CI, 0.82-1.08) or urgent PCI (HR = 1.04; 95% CI, 0.88-1.22; P for interaction = .36), Ferrari said during the press conference.
The primary safety endpoint of adverse events also yielded similar findings (trimetazidine group, 40.9%; placebo group, 41.1%; difference in annual incidences, –0.09; 95% CI, –0.99 to 0.81), according to the researchers.
Ferrari noted that there were fewer primary endpoint events than expected and, as a result, the study period was extended from 4 years to 5 years.
The mean age of the patients was 61 years and 23% were women. All had had successful PCI and were on optimal medical therapy.
"The take-home message from this study is that the patients with angina receiving optimized medical therapy to prevent angina combined with PCI have a very low event rate," Ferrari said at the press conference. "The recurrence of angina only occurs in 9% of them. Unfortunately, the improvement of cardiac metabolism with trimetazidine does not improve the outcomes or the occurrence of angina. Therefore, it is not necessary."
He said patients with chronic coronary disease “should consider themselves lucky. It is important that they control their risk factors and take the already available preventive anti-anginal drugs. If the symptoms remain, then angioplasty is indicated, and it is good.”
In a discussion after the presentation, Stephan Windecker, MD, FESC, director and chief physician of the department of cardiology at Swiss Cardiovascular Center Bern, Switzerland, said potential explanations for the lack of benefit from trimetazidine include “the much lower than expected clinical event rate ... the cardiac death rate was 0.6% per year compared with the same population in the Bern PCI registry, amounting to 3.5% at 1 year. Another potential explanation relates to the optimal medical treatment, with nearly 100% use of dual antiplatelet therapy and a high rate of anti-anginal agents ... and statin use in over 95% of patients. It also speaks to the quality of PCI performed, as only 18% had CCS class 2 to 4 angina at 1 month. Finally, it is interesting to speculate on the lack of ischemia’s impact on prognosis. In the CLARIFY registry, there has been no impact of ischemia on outcomes, and in the ISCHEMIA trial, there was no differential benefit for or against revascularization in patients with documented ischemia.”
Reference:
Perspective
Back to Top
Grant Reed, MD, MSc, FACC
The ATPCI study was a high-quality randomized controlled trial which tested whether the addition of trimetazidine would further reduce residual angina in addition to optimal medical therapy in patients recently treated with PCI. While the mechanism of trimetazidine is intriguing and holds promise, ATPCI indicated that at the dose tested trimetazidine was no more effective than placebo at reducing angina.
Were the findings to have been positive, this study could have been a game changer and opened the door to a new class of antianginal therapies. However, the results of ATPCI will likely significantly dampen enthusiasm for this agent.
One important caveat is that the event rate in the study was lower than expected, and thus the trial may have been underpowered to detect a clinical impact. That said, there was not a benefit in any subgroup of patients, suggesting that the result is real and not due to type II error.
Collapse
Ferrari R, et al. Hot Line: ATPCI. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 1, 2020 (virtual meeting).
Click Here to Manage Email Alerts