E-drug: Old drug is found to have wide benefits
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[distributed as fair and non-profit use]
The New York Times
November 11, 1999
Old Drug Is Found to Have Wide Benefits
By LAWRENCE K. ALTMAN
A drug that has been marketed for eight years to combat high blood pressure
turns out to substantially lower the risk of heart attack, stroke, bypass
surgery and diabetes and its complications in those who have heart disease,
scientists reported Wednesday.
The findings suggest that at least 10 million Americans and their doctors
may want to add the drug, ramipril, to standard heart therapies and that it
could save tens of thousands of lives each year at a cost of about 85 cents
a day, the study's chief author, Dr. Salim Yusuf of McMaster University in
Hamilton, Ontario, Canada, said in an interview.
The study was financed by the Canadian government and by the drug company
Hoechst Marion Roussel of Kansas City, Mo., which manufactures ramipril as
Altace. But scientists who were not involved in the study said they were
excited by the findings.
"The findings will have a major effect on how physicians treat patients who
have known coronary artery disease or are at high risk for it," said Dr.
Robert O. Bonow, the chief of cardiology at Northwestern University in
Chicago.
"It's a landmark study," said Dr. Bonow, who is also the chairman of the
scientific program for the American Heart Association's meeting in Atlanta,
where the paper was presented.
The study was conducted among individuals with heart or blood vessel
disease but without heart failure, Dr. Yusuf said in reporting the findings
yesterday. Participants in the study also had at least one risk factor for
heart disease or strokes, like high blood pressure, elevated cholesterol
levels or cigarette smoking.
For every 1,000 individuals who took ramipril once a day for four years,
the study found that 70 would avoid a total of 150 serious problems,
including heart attacks, strokes, the need for bypass surgery and death.
Ramipril's benefits were "at least as large" as other drugs like aspirin,
beta-blockers and those that lower lipids, Dr. Yusuf's team said, adding
that in the study ramipril had been taken in conjunction with those other
drugs, not as a substitute for them.
In the study, ramipril reduced the risk of death, heart attacks, strokes and
other problems about 20 to 25 percent beyond those achieved by the standard
drug therapies. Those are "major league reductions," Dr. Bonow said.
The findings are to be published in The New England Journal of Medicine on
Jan. 20.
Ramipril belongs to a class of drugs, ACE inhibitors, that relax blood
vessels by blocking a protein known as angiotensin-converting enzyme.
ACE inhibitors are thought to slow the progression of both heart failure and
atherosclerosis, the underlying cause of heart attacks. But more research is
needed to better understand the mechanism, Dr. Yusuf said.
Dr. Yusuf said that doctors should now consider prescribing ramipril for
those who take aspirin to prevent heart attacks and for diabetics. A clearer
picture of which other patients should receive an ACE inhibitor will come as
experts discuss the findings at future medical meetings.
It is not immediately clear whether the findings about ramipril will hold for
the 10 other ACE inhibitors on the market. That point was made yesterday at
the same meeting, in an unrelated study from the National Heart, Lung and
Blood Institute and Department of Veterans Affairs about a different class of
drugs, beta-blockers. While some beta-blockers are known to reduce death
from heart disease, scientists found that bucindolol, a beta-blocker drug,
surprisingly did not. Federal officials said they did not know why.
Dr. Bonow said, "The data seem very clear for ramipril but we do not know
now whether they convert to other ACE inhibitors."
Ramipril has been marketed in the United States since 1991 for high blood
pressure and chronic heart failure.
Dr. Yusuf said that five years ago he had performed a statistical review of
previous studies involving 9,000 patients that showed that ACE inhibitor
drugs could reduce the risk of a heart attack by 23 percent. But because the
Food and Drug Administration and others did not accept the finding, Dr.
Yusuf said he undertook the new study. It was carried out in 129 medical
centers in the United States, Canada, Mexico and South America.
Men and women at least 55 years old enrolled in the study from December
1993 to June 1995 and each was to continue in it for five years.
Participants received either ramipril or a placebo, a dummy pill, as a
scientific control. But the study was stopped ahead of schedule last March
because a safety monitoring committee found a clear benefit for ramipril in
a preliminary review.
Those eligible for the study had a history of angina, coronary artery
disease, stroke, diabetes or a painful leg condition called claudication;
they also needed at least one other risk factor for circulatory disease to be
eligible, like high blood pressure, increased cholesterol levels, low
high-density lipoprotein cholesterol or to be a cigarette smoker. More than
10,000 patients enrolled in the study.
The marked drop in the number of participants who developed diabetes and
complications from diabetes was considered a significant benefit because
diabetics are at increased risk of dying from heart attacks and strokes than
nondiabetics.
Ramipril also reduced the rates of the following compared to those receiving
a placebo: death from any cause (10.4 percent against 12.2); death from
cardiovascular causes (6.1 percent against 8.1); heart attack (9.9 percent
against 12.2); stroke (3.4 percent against 4.9); bypass surgery and
angioplasty (16 percent against 18.6 percent), and heart failure (7.4
percent against 9.4 percent).
The benefits began to appear within a year of the participants starting
ramipril and continued. A statistical analysis suggested that "longer-term
treatment might yield even better results," Dr. Yusuf said.
A persistent cough, dizziness and low blood pressure were the most common
reasons for stopping ramipril.
It is the second time within recent months that a remarkable new use was
found for an older drug. In July, researchers reported that a 40-year-old
blood-pressure drug, spironolactone, could save thousands of lives among
people with heart failure.
Speaking of the drug's potential worldwide, Dr. Yusuf said that if 50 percent
of people in developed countries and 25 percent of people in developing
countries with heart and blood vessel disease and adult onset diabetes took
ramipril, at least 500,000 deaths, 300,000 nonfatal heart attacks and
200,000 strokes would be prevented each year.
[Provided by Dzulkifli Abdul Razak
Drug Information and Poisons Centre
Malaysia and
moderator of the Drug Information Exchange for Asia-Pacific Region
<diefapr@prn.usm.my>]
Beverley Snell e-drug co-moderator.
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