STOCKHOLM — Treatment with the ACE inhibitor perindopril cut the incidence of left ventricular remodeling in elderly patients after myocardial infarction in a study with more than 1,200 patients.
As a result, treatment with the study drug, perindopril at a dosage of 8 mg/day, “may be suggested as standard treatment in this clinical setting,” Roberto Ferrari, M.D., said at the annual congress of the European Society of Cardiology.
On the basis of these results and the findings of seven previous studies, “we now have convincing evidence that all patients with coronary artery disease should get treated with an ACE inhibitor,” commented Nicolas Danchin, M.D., a professor of medicine at the European Hospital Georges Pompidou in Paris.
The latest trial, the Perindopril Remodeling in Elderly with Acute Myocardial Infarction (PREAMI) study, tested the efficacy of ACE inhibitor therapy in a very specific population: patients aged 65 or older with preserved left ventricular function following an MI.
The study enrolled 1,252 patients at 109 centers in five European countries. All patients had to have a left ventricular ejection fraction of at least 40%; the average ejection fraction was 59%, and their average age was 72 years. About 80% of patients had New York Heart Association class I heart failure. Patients were enrolled 7–20 days (a mean of 11 days) after their MI. Patients who had already begun treatment with an ACE inhibitor were withdrawn from the drug for at least 24 hours before entering the study. Almost three-quarters of the patients were on a β-blocker, which they continued to take.
Patients were randomized to treatment with either 4 mg of perindopril daily or placebo for the first month of the study, after which the dosage was raised to 8 mg daily. Patients were followed for 12 months.
The primary end point was the combined incidence of death, hospitalization for heart failure, or left ventricular remodeling. Remodeling was defined as at least an 8% rise in left ventricular and diastolic volume. Echocardiographs suitable for assessing remodeling were available a year after treatment started for 455 patients on perindopril and 441 on placebo.
The incidence of the primary end point was cut by 38% in patients treated with perindopril, compared with those on placebo, a statistically significant difference, reported Dr. Ferrari, head of cardiology at the University of Ferrara (Italy).
But the result was driven entirely by a 46% relative drop in the rate of ventricular remodeling in the perindopril-treated patients, compared with the controls. Remodeling occurred in 51% of the placebo patients and in 28% of the test group. There was no difference between the two groups in the mortality rate. And although perindopril was linked with a 27% cut in the rate of hospitalization for heart failure, this difference was not significant.
The drug was well tolerated. Its activity in reducing remodeling is probably a class effect of all ACE inhibitors, Dr. Ferrari said.
The study was sponsored by Servier, which markets perindopril (Coversyl) in Europe and elsewhere. In the United States, perindopril is marketed as Aceon by a partnership of Solvay Pharmaceuticals Inc. and CV Therapeutics Inc.