New, More Expensive Heart Drug Outpaces Old Medicine in Test : Cardiology: Treatment using t-PA reduced deaths by as much as 14% over Streptokinase, researchers find. But debate continues over the merits of the two clot-busting drugs.
One drug is old, the other new. Both are so-called clot-busters, designed to save the lives of heart attack victims by clearing blocked arteries. One costs an average of $200 a dose; the other $2,200. And for six years, cardiologists have argued over which works better.
On Friday in Washington, researchers said they have settled the long-running controversy with the world’s largest heart attack study. They found that a novel treatment employing t-PA, the newer and more expensive of the two “thrombolytic agents,” reduced deaths as much as 14% over Streptokinase, the other treatment.
“With this strategy there was no question about the benefits,” Dr. Eric J. Topol, chairman of the study and a professor of cardiology at the Cleveland Clinic Foundation, declared in announcing the long-awaited results. “We hope to put to rest the battle of the thrombolytics.”
But the debate refused to subside, as the manufacturer of the cheaper drug, Streptokinase, suggested the study was of minimal importance and may have been biased by “critical protocol violations.” The company, Astra Pharmaceutical Products, said previous research showing little difference between the two drugs should remain the “gold standard.”
The financing of the study has also created controversy, with an Astra spokeswoman suggesting in recent days that the research was designed to favor t-PA’s manufacturer--South San Francisco-based Genentech, which footed $55 million of the $65-million bill for the study. Topol, anticipating such criticism, opened Friday’s news conference by saying the research employed stringent protections against conflict of interest.
Called GUSTO--Global Utilization of Streptokinase and t-PA for Occluded Arteries--the massive, three-year clinical trial looked at 41,021 heart attack victims in 1,100 hospitals in 16 nations. The patients were as old as 110--an Israeli man who survived and is now 111--and as young as 19.
The results are expected to have a significant impact on the treatment of emergency heart attack patients around the world. The outcome is of particular interest in the United States, where doctors have tended to favor the more expensive drug even amid concerns over soaring health care costs. In Europe, more doctors use Streptokinase.
“This is really going to help us,” said Dr. Jan Tillisch, who directs the cardiac unit at UCLA Medical Center and has been following the GUSTO study closely. He praised the study as being well-designed, and added: “I think this is as close to settling (the debate) as we are probably going to get.”
The GUSTO researchers said they also proved conclusively two other hotly contested points: that clot-busting drugs--which work by dissolving blockages in arteries--improve survival among heart attack patients, and that the faster the drugs are administered, the better they work.
Experts say this finding is especially important in this country, where heart attack is the leading cause of death. An estimated 1.5 million Americans will suffer heart attacks this year, and 500,000 will likely die. Yet only one-third of U.S. heart attack victims receive clot-busting agents, as compared to more than two-thirds in Europe.
“The agents aren’t utilized in part because doctors are confused,” said Dr. Charles Hennekens, a professor at the Harvard Medical School who ran a previous study that showed little difference between the two drugs. “They say: ‘One day it’s this, one day it’s that. . . . We are having this so-called debate about which agent to use, when the real question is: Why aren’t we using it in more people?”
In a statement released after the study’s results were made public, Astra officials agreed:
“If all eligible patients received a thrombolytic agent, an additional 15,000 lives would be saved in the United States each year,” the statement said. “This remains the most important issue in thrombolytic therapy, as opposed to quibbling over minute and possibly clinically irrelevant differences between agents.”
The GUSTO researchers looked at four treatments using the two drugs, which are administered by injection. Some patients received Sreptokinase along with an injection of a heparin, which thins the blood. Some received Streptokinase with the blood thinner administered intravenously. Some received a combination of Streptokinase and t-PA with heparin, and some received t-PA with the blood thinner.
The study differed significantly from previous research in that the t-PA was administered much faster than usual. Under government guidelines, t-PA--which was approved for use in this country in 1987--may be given to heart attack patients over a three-hour period. But the GUSTO researchers, relying on past studies that showed the drug to be more effective if it is given more quickly, condensed the t-PA treatment to 30 minutes.
Topol said the same accelerated treatment could not have been performed for Streptokinase because that drug, which has been on the market for several decades, causes a dangerous drop in a patient’s blood pressure if it is given too quickly.
The study found that after 30 days, patients who received the accelerated t-PA were significantly less likely to die but had a slightly higher risk of strokes.
Dr. Robert M. Califf, a Duke University professor who was the clinical coordinator of the trial, said clot-busting drugs have reduced deaths from heart attack 25%. But the study shows that an additional 10 lives per 1,000 patients could be saved by using the t-PA regimen over Streptokinase.
Califf said the researchers also conducted a cost analysis that showed that although t-PA is expensive, the treatment is cost-effective when compared to other life-saving therapies, such as kidney dialysis.
Tillisch, the UCLA professor, suggested that the study results be examined in detail to determine if certain patients--the elderly, for instance--benefit more from t-PA than others. If that is the case, he said, the more expensive drug could be administered only to those patients who would gain the most, while others who would benefit equally from either drug could receive the cheaper Streptokinase.
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Heart Study
The world’s largest study of heart attack victims looked at 41,000 patients in 15 countries. It compared two so-called clot-busting drugs--t-PA and Streptokinase--and found that accelerated dosages of t-PA saved more lives but had a slightly higher risk of causing stroke. The study looked at deaths and strokes after 30 days with the following treatments: TREATMENT: t-PA plus intravenous blood thinner DEATHS*: 6.3% STROKES: 0.6%
TREATMENT: t-PA, Streptokinase plus intravenous blood thinner DEATHS*: 7.0% STROKES: 0.6%
TREATMENT: Streptokinase plus blood thinner given by injection DEATHS*: 7.2% STROKES: 0.5%
TREATMENT: Streptokinase plus intravenous blood thinner DEATHS*: 7.4% STROKES: 0.5% * Death rate after 30 days
