A new clot-preventing drug called bivalirudin is much more effective than existing drugs at stopping clot formation during balloon angioplasty for severe heart attacks, reducing the risk of death by a third, researchers reported today.
The results "provide an advance over what the standard for treatment was," said Dr. Gregg C. Fonarow, a cardiologist at UCLA's Geffen School of Medicine who was not involved in the research. "Many large centers have begun using it already and, with the publication of this trial, we'll see even greater use."
In a second study, researchers found that combining angioplasty with a different drug that dissolves, rather than prevents, clots provided no benefit for survival and doubled the risk of major bleeding episodes.
"It is time to abandon the routine use of" the method until researchers can find a better and safer way to perform it, said Dr. Jane A. Leopold of Brigham and Women's Hospital in Boston, who was not involved in the research.
The two studies are likely to subtly change the way emergency physicians treat major heart attacks, improving the safety of the procedures and increasing chances of survival.
Both reports, published in the New England Journal of Medicine, dealt with the most severe form of heart attack, in which a clot almost totally blocks one of the arteries supplying blood to the heart. Such episodes account for about 30% of the estimated 1 million heart attacks that strike Americans each year.
Angioplasty, which involves physically compressing the clot with a balloon threaded through the artery, is now the preferred method for opening arteries because it has a significantly higher success rate.
To minimize formation of new clots during and after angioplasty, surgeons typically use a combination of blood-thinning drugs and clot-preventing agents.
Dr. Gregg W. Stone of Columbia University Medical Center and his colleagues tested whether bivalirudin, which is marketed by the Medicines Co. under the brand name Angiomax, could do better than older clot preventers.
Bivalirudin is an analog of an anti-clotting agent originally found in the saliva of leeches. It only works for a short period of time, so there are fewer side effects.
Stone's team studied 3,603 patients undergoing angioplasty for a severe heart attack. Roughly half of the group received bivalirudin, while the rest received the standard treatment of heparin, a blood thinner, plus one of the older clot-preventing drugs.
The patients who received bivalirudin were 33% less likely to die in the first 30 days after the procedure and 38% less likely to die of a heart attack, the team reported.
The study was "the first trial since the introduction of balloon angioplasty to show improved survival," Stone said.
Dr. Robert S. Greenfield, a cardiologist at Orange Coast Memorial Hospital in Fountain Valley, who was not involved in the study, said surgeons were already starting to use bivalirudin because it gave "improved survival, less bleeding and less need for blood transfusions. It has caught on real quickly."
The study was supported by the Cardiovascular Research Foundation, Boston Scientific, which makes angioplasty equipment, and the Medicines Co. The authors reported receiving grants from various pharmaceutical companies.
Angioplasty is most effective when given within 90 minutes after a heart attack. Some doctors have argued that if the procedure is delayed beyond 90 minutes, physicians can buy time by using either a clot-preventing agent, a clot-dissolving drug, or both.
Others have argued that combining angioplasty and clot-dissolving drugs -- both of which are effective therapies -- should produce even better results.
To test those theories, Dr. Stephen G. Ellis of the Cleveland Clinic and his colleagues studied 2,452 patients who had a severe heart attack. A third of them were given only angioplasty; a third received a clot dissolver called reteplase plus the clot-preventing drug abciximab before they underwent angioplasty; and a third received only abciximab before the procedure.
The researchers found that the death rate was about 10% in all three groups.
"There was not much in the way of clinical gain for a typical patient, and the bleeding was essentially doubled" in the two groups that received drugs, Ellis said.
He noted that few doctors used clot dissolvers in combination with angioplasty any more, but that many still used abciximab as a holding treatment when angioplasty was delayed.
"Physicians feel they ought to be doing something, but there is not much data to support that," Ellis said.
The trial was sponsored by Centocor Inc. and Eli Lilly & Co., which sell abciximab under the brand name ReoPro. The companies terminated the study prematurely, Ellis said, when costs escalated and it became clear that there would be no benefit.