ATLANTA -- The eagerly awaited ISIS-3 study of heart attack therapieshas concluded that streptokinanse is as effective and safer thancompeting and more expensive clot-dissolving drugs.
In results announced here Saturday at the American College of Cardiologyconvention, ISIS-3 researchers "found no significant differences betweenthe numbers of lives saved by an inexpensive 30-year-old drug,streptokinase, and the 10 times more expensive t-PA or APSAC" (Eminase).
The researchers also said streptokinase was safer because both Eminaseand tissue plasminogen activator (t-PA) caused "significantly" more strokes.
The 46,000-patient International Study of Infarct Survival-3 (ISIS-3) trialalso concluded that heart attack survival could be improved by supplementingaspirin with moderate doses of another anticoagulant, heparin..To compare clot-dissolving drugs, patients received SmithKline BeechamCorp.'s Eminase; Hoechst-Roussel Pharmaceuticals Inc.'s streptokinase; orduteplase, an unapproved form of t-PA produced by Burroughs Wellcome Co.
Summing up ISIS-3, trial coordinator Dr. Rory Collins told BioWorld,"If I had a heart attack, I'd ask for aspirin followed by streptokinase."
Genentech Responds Quickly. Although its version of t-PA wasn't tested,Genentech Inc. of South San Francisco, Calif., has the most to lose fromdata that don't show any clear benefit from t-PA. Genentech, with theonly t-PA approved in the United States, controls 64 percent of thethrombolytic market. It sells Activase for about $2000 per dose, comparedto $200 charged for streptokinase and $1,700 for Eminase. Activaseaccounted for $210 million in sales in 1990, about half of Genentech'srevenue.
The ISIS researchers said, "If U.S. physicians began to use SK(streptokinase) routinely instead, this might avoid hundreds of strokesa yearHand, it would save more than $100 million a year."
On Sunday, Genentech issued a statement saying the application ofthrombolytics in ISIS-3, particularly in the absence of intravenousadministration of heparin, was not in keeping with U.S. physician practices.
"This use of continuously administered intravenous heparin with Activasehas been demonstrated to be safe and effective in treating thousands ofheart attack patients to date," the company said.
Dr. David C. Stump, Genentech director of clinical research, said"ISIS-3 is pertinent only for the comparison of SK and Eminase."Last week, SmithKline agreed in federal court not to imply in itsadvertising that Activase was used in ISIS-3.ISIS-3 AT A GLANCE
Purpose: To study the benefits and risks of two therapeutic regimens forheart attack: thrombolytics to dissolve clots and anticoagulants toprevent them.
Thrombolytics studied were streptokinase, APSAC (Eminase, made bySmithKline Beecham Co.), and t-PA (duteplase, produced by BurroughsWellcome Co.) Anticoagulant regimens studied were aspirin alone vs. aspirinplus heparin.
Study Population: 46,000 heart attack patients from 1000 hospitals in20 countries.
-- Mortality rates for thrombolytics were 10.5 percent for patientsreceiving streptokinase, 10.6 percent for Eminase, and 10.3 percent for t-PA.
-- The risk of stroke was 3 per thousand for those receiving streptokinase,6 per thousand for Eminase and 7 per thousand for t-PA.
-- Patients receiving streptokinase had 5 more re-infarctions (secondheart attacks) per thousand than patients receiving t-PA.
-- Using heparin in addition to aspirin caused 5 fewer deaths per 1000patients but 2 more cerebral hemorrhages.
Funding and Support: About $8 million was granted to the University ofOxford, England, by Burroughs Wellcome and by Smith-Kline Beecham.
THE OFFICIAL SUMMARY OF ISIS-3 IS AVAILABLE ON BIOWORLD ONLINE. THE KEYWORDIS 0304ISISTEXT.
-- Karen Bernstein BioWorld Staff
(c) 1997 American Health Consultants. All rights reserved.