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                   Copyright 1993 The Times Mirror Company                      
                               Los Angeles Times                                
                                                                                
                      May 1, 1993, Saturday, Home Edition                       
                                                                                
SECTION: Part A; Page 25; Column 1; Metro Desk                                  
                                                                                
LENGTH: 1162 words                                                              
                                                                                
HEADLINE: 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.                                                         
                                                                                
BYLINE: By SHERYL STOLBERG, TIMES MEDICAL WRITER                                
                                                                                
 BODY:                                                                          
   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.                                                                 
                                                                                
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         
                         Los Angeles Times, May 1, 1993                         
                                                                                
 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