Drug Mix Cuts Heart Attacks, Study Says
Daily doses of aspirin and the blood thinner warfarin can reduce the incidence of first heart attacks by more than a third among men who are at high risk of heart disease, British researchers report.
That combination of drugs is currently used to help prevent second heart attacks, but the new study, to be reported Saturday in the medical journal Lancet, is the first to investigate the drugs’ use among men who have not had an attack.
At least 1.5 million Americans will suffer a heart attack this year, with one-third of the attacks being fatal.
Surgeons have not used both drugs together in high-risk patients in the past, because the combination increases the likelihood of bleeding in the brain, said Dr. Thomas W. Meade of the Royal London School of Medicine, who headed the study.
“But we found that warfarin and aspirin together prevented 12 heart attacks for every cerebral hemorrhage or fatal stroke,†he said. “That’s a very beneficial ratio.â€
The study “opens the door†to new treatments for preventing heart attack deaths in healthy individuals at high risk, said Dr. Valentin Fuster of the Mt. Sinai Medical Center in New York, president-elect of the American Heart Assn. With the dosages the researchers used, he added, “the benefits outweighed the risk.â€
Fuster cautioned, however, that more research is necessary before physicians start recommending the combination to high-risk men.
Meade noted that most of the hemorrhages and strokes among patients receiving the combination occurred in men with high blood pressure. Fuster concurred: “Physicians must first make sure that, before prescribing the combination, patients must have their high blood pressure controlled.â€
The study involved 5,085 men, ages 45-69, being treated in 108 private practices in the United Kingdom. Each patient was assigned a “score†computed by a formula that ranked their history of smoking, blood pressure, obesity, cholesterol levels and concentrations of two proteins in their blood associated with clotting.
The 5,085 men were all in the top 20% of such scores, indicating that they ran a high risk of having a heart attack. Different groups received either a placebo, aspirin alone, warfarin alone or a combination of the two drugs. Warfarin is marketed under the brand name Coumarin.
The two drugs apparently acted independently. Aspirin alone produced a 32% reduction in nonfatal heart attacks, but had no effect on the incidence of fatal heart attacks. Warfarin had the opposite effect: It produced a 39% reduction in fatal heart attacks, but had no effect on nonfatal ones.
The report “is significant in that it shows that aspirin alone is very useful in men at high risk,†said Dr. Pan Ganguly of the National Heart, Lung and Blood Institute. Many physicians are already using it for that purpose, he noted, but researchers have never been sure that it is beneficial. The British study “adds strength†to that idea, he said.
The combination of drugs reduced both fatal and nonfatal heart attacks, leading to an overall 39% drop in heart attacks.
Meade said that among each 1,000 men in this high-risk category, 14 would be expected to have a heart attack during any given year. Treating those 1,000 men for a year with either drug would prevent about three of those heart attacks. Treating the group with both drugs would prevent five.
Over the 13-year course of the study, there were 3.6 strokes per 1,000 men per year in the combination group, compared to 3.2 in the placebo group, 2.7 in the warfarin-only group, and 2.2 in the aspirin-only group.
In addition to this slightly increased risk in the combination group is the relatively high cost of warfarin treatment. The drug itself is not unusually expensive, but patients must see their doctor every three months, Meade said, to have several tests performed on their blood.
That makes warfarin considerably more expensive than aspirin, but still much less expensive than drugs used to lower cholesterol. Cholesterol lowering reduces first heart attacks by about the same amount as the two drugs in this study. It is not yet known if combining cholesterol lowering drugs with the warfarin/aspirin regimen will produce a much greater drop in heart attacks than using either alone, Meade said.
The study did not include women. Meade said that studying women would require a much larger patient group because the incidence of heart attacks in that age group is much lower than it is in men. Women generally develop heart disease about 10 years later than do men.
Ganguly noted, however, that the aspirin findings could probably be extrapolated to women. That has been the case with other aspirin studies.
The study was funded by aspirin manufacturer Bayer Corp. and warfarin maker DuPont Merck Pharmaceutical Company. According to a DuPont spokesman, 3 million Americans are taking warfarin for treatment of heart disease.
