Use of the angiotensin converting enzyme inhibitor (ACE inhibitor) ramipril significantly reduces development of heart failure in high-risk patients, according to an article in the February 25th rapid access issue of Circulation.

“This trial extends the benefits of ACE inhibitors beyond what has been previously proven,” said lead author Malcolm Arnold, M.D. “It shows, for the first time, that heart failure can be prevented in a broad range of high-risk patients.”

Canadian researchers found that ramipril reduced the risk of heart failure by 23 percent in patients with cardiovascular disease who had normal ejection fractions and no previous history of heart failure. Patients who received the drug also had a lower rate of hospitalization and death due to heart failure.

“The reduction of heart failure in people treated with ramipril was consistent in all major subgroups,” said Arnold. “These included patients over 65 years, females, and patients without known hypertension or diabetes.”

The current study is derived from the Heart Outcomes Prevention Evaluation (HOPE) study, a randomized trial that followed 9,541 high-risk cardiovascular patients age 55 years and older at 267 centers in 19 countries in the Americas and Europe. Researchers used data from 9,297 patients who had randomly received either 10 milligrams of ramipril or placebo daily and were followed for an average of 4.5 years. Their average age was 66 years; 73 percent were male. The majority (53 percent) had a previous myocardial infarction, 47 percent had a history of hypertension, and 38 percent had diabetes.

Heart failure developed in 951 (10.2 percent) of the participants during the follow-up period. Ramipril reduced the rate of heart failure by a significant 22 percent in the 8,315 patients who did not have a myocardial infarction. Among the 1,029 people who had an infarction, patients on ramipril had a 13 percent lower rate of heart failure, although this finding did not reach statistical significance.

In addition, patients treated with ramipril whose systolic blood pressure was above the median had a 33 percent reduction in risk of heart failure compared with a 9 percent reduction for those with a systolic reading below the median.

In an accompanying editorial, Jennifer V. Linseman, Ph.D., and Michael R. Bristow, M.D., Ph.D., noted that a majority of the participants in this analysis were classified with heart failure when their symptoms became severe enough to warrant treatment with an ACE inhibitor. Because of this “softer endpoint than death or hospitalization,” the results, “while still encouraging, should be viewed with some caution.”

Taken with previous results from the larger study, the editorial writers said “these data support the idea that ACE inhibitors exert a measurable cardiovascular-protective effect in a broad range of patients at high-risk of cardiovascular complications, and these effects are additional to and independent of blood pressure lowering.”