ESC/WCC: Acenon (perindopril) Plus Diuretic Fails to Reduce Heart Failure Mortality

BARCELONA, Spain, Sept. 4 -- Acenon (perindopril) plus a diuretic was not a winning combination for reducing heart failure deaths, but it may ease symptoms and improve exercise capacity, according to a trial reported here.

After 12 months, the mortality rate was lower (10.8%) among elderly patients treated with the Acenon-diuretic combination than it was in the placebo arm (15.3%), although that difference was not statistically significant (P=0.055), said John Cleland, M.D. of the University of Hull in Hull, England.

Dr. Cleland reported the results of the PEP-CHF (Perindopril in Elderly People with Chronic Heart Failure) trial at the European Society of Cardiology/World Congress of Cardiology meeting.

Despite the lack of statistical significance, there were some hopeful signals from the combined regimen, said Dr. Cleland. For example, patients treated with the Acenon had fewer unscheduled hospitalizations for heart failure (8% versus 12.4%) and that difference was significant (P=0.033).

The PEP-CHF trial recruited 850 patients, which was fewer than the 1,000 in the study protocol, which may explain why the trial failed its primary endpoint, Dr. Cleland said.

All patients were 70 or older who had a heart failure with preserved left ventricular function (LVEF of 45% or higher) and evidence of possible diastolic dysfunction on echocardiographic studies. Four hundred and twenty-four patients were randomized to 4 mg of Acenon plus a thiazide-type diuretic and 426 to placebo plus a diuretic.

Additional analysis yielded several findings that were significant or just missed statistical significance.

Those findings:

• Among patients 75 or younger the Acenon treatment was associated with a significant reduction in the combined endpoint of heart failure mortality or hospitalization (P=0.035).
• Patients with prior myocardial infarction had a significant reduction in mortality and hospitalizations (P=0.004).
• In patients with systolic hypertension there were fewer deaths and hospitalizations, but this was not significant (P=0.055).

Of interest, there were significant improvements in NYHA functional class (P<0.03) and improvement in six-minute walk distance (P=0.02).

Taken together, Dr. Cleland said, those results suggest that this combination may benefit elderly patients who have preserved left ventricular function, but he said he could not make that recommendation on the basis of the data.

Kenneth Dickstein, M.D., of the University of Bergen in Stavanger, Norway, was more enthusiastic. Dr. Dickstein, who served as discussant for the study, said that the PEP-CHF results, along with results of the CHARM-Preserved trial, which investigated Atacand (candasartan), an angiotensin II inhibitor, in a similar population, provide evidence that drugs that block the renin-angiotensin system may have a role in treating systolic dysfunction heart failure.