A drug commonly used to treat people with congestive heart failure apparently could help save the lives of many more people than previously known, preventing heart attacks, strokes and sudden death among those merely at risk for the disease, researchers reported yesterday.
Ramipril, a member of the ACE inhibitor family of medicines, reduced the death rate of elderly people with cardiovascular disease but without congestive heart failure, a condition that kills about half its sufferers in five years. Curiously, there were also fewer new cases of diabetes in people taking the drug.
The study, which lasted nearly five years, involved 9,200 people in 19 countries. Its results were released two months before they are scheduled to appear in the New England Journal of Medicine because of the potential public health implications.
"I think this was a really important trial," said Rose Marie Robertson, a cardiologist at Vanderbilt University and president-elect of the American Heart Association, at whose annual meeting the findings were released yesterday. "The impact was so significant, and it extends the indication [for use of the drug] to a much larger group of patients."
The number of people who might benefit from ACE inhibitors, but aren't taking them now, is unknown, but probably numbers in the millions.
About 14 million Americans alive today have experienced angina pectoris--chest pain caused by insufficient blood flow to the heart muscle--or have had a heart attack. About 600,000 have had a stroke. Although ACE inhibitors are used by a minority of people in both groups, the new study suggests many more could benefit from them.
About 1 out of every 14 people treated with the once-a-day drug benefited from it, an unusually good "yield" for a medical intervention designed to prevent future problems and not cure an existing one.
"It opens new avenues for prevention of heart disease and diabetes," said Salim Yusuf, a cardiologist and epidemiologist at McMaster University, in Ontario, who headed the huge study.
ACE inhibitors block production of a hormone that both causes blood vessels to constrict and contributes to the body's regulation of salt. First approved to treat high blood pressure, the drugs have grown steadily in usefulness in the last 15 years as researchers have elucidated beneficial effects on the heart, kidneys, blood vessels and endocrine system. Their apparent ability to prevent some cases of adult-onset diabetes is the latest unexpected finding.
There are currently more than a half-dozen of the drugs on the U.S. market. Although they haven't been specifically approved for the broad preventive use suggested by the new study, doctors are permitted to prescribe them for any reason. Only ramipril was studied, however, and whether other ACE inhibitors will have effects of similar magnitude is unknown.
ACE inhibitors can cause dizziness, chronic cough and, in rare cases, a life-threatening swelling of tissues of the throat. About one-third of people in the study stopped taking the drug. Roughly the same fraction of people on placebo also stopped taking their pills.
Overall, it's not a great surprise the people in the HOPE study--the acronym is for Heart Outcomes Prevention Evaluation--benefited from an ACE inhibitor. They all had some health problem known to raise the risk of cardiovascular disease and death. What they didn't have was a reduction in the heart's pumping ability, a condition caused by severe heart attacks or decades of poorly treated hypertension. That finding is an ominous sign, and often marks a downward course toward disability and death.
In the study, about 4,600 people were randomly assigned to take ramipril and a similar number assigned to placebo. Their average age was 66, and about one-quarter were women. About 80 percent had evidence of coronary artery disease, such as angina or a previous heart attack. About 10 percent had had strokes. Each person also had at least one additional problem--such as diabetes, high blood pressure or elevated cholesterol--that increased their risk of cardiovascular problems.
After nearly five years in the study, 14.1 percent of people taking ramipril had suffered a heart attack, stroke or death from cardiovascular causes. In the placebo group, 17.7 percent of people had suffered such events. Overall, 10.4 percent of people taking ramipril had died, compared to 12.2 percent of people on placebo. In the ramipril group, 3.7 percent of people had developed diabetes, compared to 5.3 percent of people in the placebo group.
The study also tested the usefulness of vitamin E in the prevention of cardiovascular disease, assigning patients to take 400 units of the vitamin or a placebo. Vitamin E had no effect, good or bad, Yusuf said.
The ramipril study will be published in the New England Journal of Medicine in January. The journal is reviewing the vitamin E part of the study, and declined to reveal details of it.