June 10, 1998 DALLAS, June 9 -- A type of drug that lowers high blood pressure improves a person's odds of surviving after a heart attack, say researchers reporting on a study of nearly 100,000 heart attack patients that appears in today's Circulation: Journal of the American Heart Association.
The drugs, called an ACE (angiotensin-converting enzyme) inhibitors, interfere with the body's production of a chemical called angiotensin that causes the blood vessels to constrict. When blood vessels widen, blood pressure is lowered. The study found that for every 1,000 individuals treated, five lives were saved after 30 days, says Maria Grazia Franzosi, Ph.D., a pharmacologist at the Istituto di Ricerche Farmacologiche "Mario Negri" in Milan, Italy, who led the collaborative analysis.
"For most individuals, ACE-inhibitor therapy may be started immediately -- during the first few hours of a heart attack," she says. "Most of the benefit appears early, in the first few days, when the risk of death is highest." In an accompanying editorial in the journal, Marc A. Pfeffer, M.D., Ph.D., of the cardiovascular division of Brigham and Women's Hospital at Harvard Medical School in Boston, writes, "ACE-inhibitors have earned their place" along with aspirin and drugs such as beta-blockers and thrombolytic therapies proven to reduce deaths from heart attack.
Thrombolytic, or "clot-busters" and aspirin break up blood clots that can obstruct the blood vessels leading to the heart, while beta-blockers and ACE-inhibitors relax the blood vessels.
On the downside, ACE-inhibitors nearly doubled the risk of low-blood pressure episodes. The rate of such episodes was 17.6 percent in the drug-treated group and 9.3 percent in the control group of patients who were not treated with the drug. Those taking the drug also had double the rate of kidney problems: 1.3 percent in the drug group versus 0.6 percent in controls. The researchers lack data on whether those conditions improved when treatment was stopped. Those two complications were much more common in people over age 75, and there was no evidence of a survival advantage among them. "However, there was no subgroup in which the treatment was shown to be definitely harmful," she says. Grazia Franzosi conducted the study to identify subgroups of individuals in whom the drugs would be particularly beneficial and to determine their overall effect in reducing deaths from heart attacks. The study combines four large-scale drug trials in Australia, Canada, China, Europe, the Mediterranean, Scandinavia, South Africa and South America.
In each study, people receiving ACE-inhibitors were compared to the control group. ACE-inhibitors were given within 36 hours of heart attack symptoms and continued for up to six weeks. After 30 days, the death rate from heart attack was reduced by seven percent in the treatment group compared to the control group.
Most of the deaths were prevented --about 80 percent -- during the first week, when heart attack risk is highest. The low-risk group, those who were younger and with fewer medical problems, experienced four fewer deaths per 1,000 treated with ACE-inhibitors.
Grazia Franzosi recommended two strategies for using ACE inhibitors. One is to treat people who do not have clear reasons to avoid the drug, such as systolic blood pressure under 100 millimeters/mercury. Such treatment could be re-evaluated before the person leaves the hospital or after a few weeks and continued long-term only in those at high risk due to other health problems. A second strategy is to use the drugs early only in certain high-risk individuals such as those with irregular heart rhythms, heart failure and, possibly, diabetes.
"Irrespective of which strategy physicians choose, the results of this analysis support the use of ACE-inhibitors early in the treatment of heart attack," she says.
"The absolute benefits were greater in high-risk individuals: About four lives were saved per 1,000 low-risk patients compared to 13.6 lives saved in very high-risk individuals," Grazia Franzosi says. Patients at high risk were those with low blood pressure, high heart rate, previous heart attack, diabetes or hypertension. People whose heart attacks were localized to the anterior region of the heart also were at high risk. They had a 14 percent lower risk of death.
Less than 40 percent of the heart attacks studied were in that part of the heart.
A group with heart rates over 100 beats per minute (bmp) had 22.7 fewer deaths per 1,000; The group with heart rates between 80-99 bpm had 8.7 fewer deaths per 1,000. Other high-risk groups -- those who had previously had a heart attack and those with diabetes or high blood pressure -- benefited more from ACE-inhibitor treatment.
In addition, the drug therapy reduced the rate of heart failure -- a major cause of heart attack disability -- by six cases per 1,000 in the first 30 days. One of the four studies, which formed the basis for this data, the GISSI-3 study in Italy, found that ACE-inhibitors given for 42 days reduced heart failure at a rate of eight per 1,000. Heart failure is a condition that occurs because the heart muscle is damaged or overworked.
Co-authors are: E. Santoro, M.S.; G. Zuanetti, M.D.; R. Latini, M.D.; A.P. Maggioni, M.D.; and G. Tognoni, M.D., all of the Instituto di Ricerche Farmacologiche "Mario Negri," Milan; C. Baigent, M.S.; R. Collins, M.B., B.S.; and P. Sleight, M.D., from the ISIS Group at the University of Oxford, U.K.; L. Li-Sheng, M.D. from Fu Wai Hospital, Beijing; M. Flather, M.B., B.S., Royal Bromptom Hospital, London; J. Kjekshus, M.D.; University of Oslo, Norway; K. Swedberg, M.D., University of Goteborg, Sweden; and S. Yusuf, M.D., McMaster University, Hamilton, Canada.
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