Ramipril reduces rate of sudden cardiac death and nonfatal cardiac arrest by 21 percent

Ramipril, a high blood pressure and heart failure drug, can reduce the rate of sudden cardiac death and nonfatal cardiac arrest by 21 percent in people at high risk for heart attack or stroke, according to a study reported in Circulation: Journal of the American Heart Association.

Drugs like ramipril, which is an angiotensin-converting enzyme (ACE) inhibitor, are often used to treat heart failure or left ventricular systolic dysfunction. But patients in the study did not have either condition, said Koon K. Teo, M.B., Ph.D., lead author of the study.

The researchers analyzed data from the Heart Outcomes Prevention Evaluation (HOPE) study, which enrolled 9,297 men and women (average age 66) at high risk for heart attack or stroke. Researchers randomly assigned subjects to ramipril, vitamin E or a placebo. The researchers found that ramipril demonstrated a protective effect while vitamin E did not prevent heart attack or stroke. But the initial report did not include data on sudden death or nonfatal cardiac arrest.

After an average of 4.5 years of treatment, 155 events (132 sudden cardiac deaths and 23 resuscitated cardiac arrests) occurred in the ramipril group; 195 events (162 sudden deaths and 33 resuscitated arrests) occurred in the placebo group. There were no significant differences in outcomes between patients assigned to vitamin E therapy and those given a placebo. The vitamin E arm was not further considered in this study. Overall, 3.3 percent of the ramipril group had either sudden cardiac death or nonfatal cardiac arrest compared to 4.2 percent of the placebo group.

Other studies have reported similar protective effects for other ACE inhibitors, but Teo said the HOPE data provides a big sample size to confirm this benefit.

Ramipril was the only ACE inhibitor used in the HOPE study. But “since these findings have been reported with other ACE inhibitors, I think it would be correct to say that this risk reduction is a class effect,” said Teo, professor of medicine at McMaster University in Hamilton, Ontario, Canada.

ACE inhibitors are recommended for treating heart failure, hypertension and people at high risk for cardiovascular events, but Teo said the drugs may be underused.

“The new findings should remind physicians of the importance of ACE inhibitor therapy,” he said. “We now know that these drugs are not only good in preventing overall cardiovascular death, but also in preventing specific causes of death.”

However, Teo said researchers aren’t suggesting that ramipril be used by itself to prevent sudden cardiac death or nonfatal arrest in people at high risk.

High-risk patients often require a combination of many agents, he said. For example, in the HOPE study, 76.3 percent of participants were taking an antiplatelet drug; 28.9 percent were taking lipid-lowering drugs; 39.5 percent were taking a beta-blocker; 47 percent were taking a calcium channel blocker; and 15.1 percent were taking diuretics.

Co-authors are L. Brent Mitchell, M.D.; Janice Pogue, M.Sc.; Jackie Bosch, M.Sc.; Gilles Dagenais, M.D.; and Salim Yusuf, FRCP, DPhil.

The Medical Research Council of Canada and Aventis Pharma, Inc., funded the study.