ACE Inhibitor Beneficial for Older Patients with Diastolic

June 3, 2007
Wayne Kuznar

Internal Medicine World Report, October 2006, Volume 0, Issue 0

From the World Congress of Cardiology

Barcelona?In older patients with chronic heart failure (CHF) and preserved left ventricular (LV) function, now referred to as diastolic heart failure (HF), the angiotensin-converting-enzyme (ACE) inhibitor perindopril (Aceon) improves symptoms and functional capacity when used for a 2-year period and may also provide benefits in the first year of treatment.

Although the study did not show a significant reduction in the combined incidence of mortality and unplanned HF-related hospitalizations with perindopril, it did show a strong trend toward clinical benefit during the first year of treatment, including a significant reduction in the number of unplanned HF hospitalizations.

In the Perindopril in Elderly People with Chronic Heart Failure (PEP-CHF) study, a high crossover from placebo to perindopril at 12 to 18 months and a lower-than-anticipated event rate may have been responsible for the nonsignificant effect of perindopril on the primary end point?a composite of mortality and unplanned hospitalization for HF?said lead investigator John Cleland, MD, of the University of Hull, Castle Hill Hospital, Kingston Upon Hull, England, who presented these findings during the 15th World Congress of Cardiology.

Nevertheless, PEP-CHF represents "the first study to show a clear effect in improving symptoms [in diastolic HF] with a therapy other than diuretics," observed Dr Cleland.

In the trial, patients aged ≥70 years with clinical evidence of HF secondary to LV diastolic dysfunction were randomized to placebo or to perindopril, beginning at 2 mg/day and titrated to 4 mg/day.

Investigators planned to recruit 1000 patients but stopped at 850 patients because of the slow pace at which patients were entering into the trial, a situation that is not unusual in clinical trials of older patients, said Dr Cleland.

Furthermore, blinded therapy was stopped in 40% of patients assigned to perindopril and in 36% assigned to placebo at 18 months. According to Dr Cleland, crossover to open-label ACE inhibitor therapy was the main reason for discontinuing blinded therapy.

At a median of 2.1 years, the incidence of the primary end point was reduced by 8% in the perindopril recipients relative to the placebo group. This difference failed to achieve statistical significance.



Despite the high crossover rate, patients assigned to perindopril spent a median of 5 fewer days in the hospital for any reason ( = .16) and 3 fewer days for cardiovascular reasons (?= .0557) compared with those assigned to placebo.

During the first year, 10.8% of those receiving perindopril and 15.3% of those receiving placebo had a primary outcome event, which almost reached significance (P?= .055).

There was a nonsignificant 37% reduction in unplanned HF hospitalizations in the perindopril group during the first year (P?= .033).

Furthermore, New York Heart Association functional class was significantly more likely to improve in patients randomized to perindopril (P <.03). This group also had a greater increase in their 6-minute walking distance (21 vs 8 m; P?= .02).

Dr Cleland said that the improvements with perindopril occurred in a population that was already being well-treated; 55% were taking beta-blockers, 67% were taking aspirin, and nearly all were taking diuretics (55%, thiazide diuretics and almost half, loop diuretics).

Many physicians have already been using an ACE inhibitor or an angiotensin receptor blocker to treat patients with diastolic HF. "The results should encourage physicians to continue to do what they're doing," he said. "If anything, they have new evidence that they can use an ACE inhibitor."