Source: Pharmacotherapy  |  Posted 5 years ago

By Joanna Lyford

BARCELONA, SPAIN -- September 6, 2006 -- The angiotensin converting enzyme (ACE) inhibitor perindopril improves symptoms and functional capacity and prevents hospitalizations in elderly people with diastolic heart failure, according to results of the Perindopril in Elderly People with Chronic Heart Failure (PEP-CHF) trial.

In a presentation here on September 3[^]rd[] at the European Society of Cardiology World Congress of Cardiology (WCC), researchers said that adding perindopril to standard treatment reduced various measures of morbidity.

In the PEP-CHF trial, participants were diagnosed with diastolic heart failure, a little-studied form of chronic heart failure characterized by diastolic dysfunction and normal left ventricular systolic function.

Although deaths were not significantly prevented by perindopril, this was largely attributed to methodological shortcomings of the study. Accordingly, the researchers interpreted the results as supporting a role for inhibition of the renin-angiotensin system in this poorly understood disease.

"Other important measures were strongly supportive," commented principal investigator John Cleland, MD, cardiologist, Castle Hill Hospital, Kingston-upon-Hull, United Kingdom. "Clinicians will understand the message."

One of a handful of trials to focus solely on diastolic heart failure, PEP-CHF included 852 patients aged 70 years and over with a clinical diagnosis of heart failure, normal systolic function, and echocardiographic evidence of diastolic dysfunction. Participants were randomly assigned to take perindopril 2 to 4 mg/day or placebo, in addition to their usual medical therapy.

Speaking at a Hotline session, Dr. Cleland revealed that the study failed to meet its primary endpoint. After a median follow-up of 2.1 years there was no significant difference between the treatment arms in the risk of all-cause mortality or heart failure hospitalization (Hazard Ratio 0.92, []P[] = NS).

Dr. Cleland also presented a separate analysis, which looked at events that occurred during the first year of follow-up. The rationale for this was the extremely high proportion of patients who switched to open-label ACE inhibitor therapy in the second year of the study.

In this post hoc analysis, during which most subjects were still taking their original study medication, the perindopril arm showed a number of benefits compared with the placebo arm. These included reductions in the primary endpoint, heart failure hospitalizations, and the combination of cardiovascular death and heart failure.

The ACE inhibitor was also associated with significantly less morbidity, as indicated by fewer days spent in hospital, improvements in New York Heart Association functional class, and better performance in the 6-minute hall-walk test in perindopril-treated patients versus controls.

"The results suggest that perindopril is of benefit in this elderly population," Dr. Cleland concluded. "This is a clinically important study as the prevalence of heart failure increases substantially with age. No other agent has been shown to be effective in relieving symptoms, improving functional capacity, or reducing morbidity in older patients with heart failure and diastolic dysfunction."

[Presentation title: The Perindopril in Elderly People With Chronic Heart Failure (PEP-CHF) Study. Abstract 984]