"Money is no object, doctor! Spare no expense!" This has been thetraditional plea of worried patients and anxious families, whosephysicians warn of costly medical measures.

Nowadays, and increasing in the future, affordability enters theequation. It surfaced starkly circa 1987, when Genentech Inc.'s newheart-attack clot-buster, recombinant tissue plasminogen activator (t-PA), came to market with a price tag of $2,200 per dose _ nearly 12times the tab for streptokinase, at $186.

While Genentech's genetically engineered drug quickly engulfedtwo-thirds of the $300-million market for opening clogged coronaryarteries, health-care providers as well as cardiologists began askingwhether Activase (Genentech's trademarked t-PA) was 12 timesbetter than streptokinase _ or better at all. An escalating series ofclinical trials worldwide has been trying to answer that multimillion-dollar question ever since.

Now the largest study of them all, GUSTO (Global Utilization ofStreptokinase and Tissue Plasminogen Activator for OccludedCoronary Arteries) comes up with a quantified, qualified, but clearanswer: Yes, t-PA, despite its added expense, is overall a statisticallybest buy.

Curiously, this long-awaited verdict reached the professional publicthis week separately in the two leading (and competing) journalsaddressed to doctors: The New England Journal of Medicine(NEJM), dated May 25, and the Journal of the American MedicalAssociation (JAMA), May 24/31. At least as strange, six of the 15multinational co-authors in the NEJM also figure among the dozenJAMA authors.

NEJM's "Special Article" bears the title: "Cost Effectiveness ofThrombolytic Therapy With Tissue Plasminogen Activator AsCompared With Streptokinase for Acute Myocardial Infarction."

JAMA heads its report: "Variations in Patient Management andOutcome for Acute Myocardial Infarction in the United States andOther Countries: Results From the GUSTO Trial."

GUSTO is by far the most massive of the successive clinicalcardiological studies that pitted t-PA against streptokinase. Itrandomized 41,021 heart-attack victims at 1,081 cardiac sites in 15countries between the two drugs. (See BioWorld Today, Sept. 7,1993, p. 1.)

GUSTO's protocol actually compared the outcomes of fouralternative forms of treatment, rather than merely testing one drugagainst the other: streptokinase plus intravenous heparin;streptokinase plus subcutaneous heparin; t-PA by accelerated dosage,plus intravenous heparin; and a mixture of t-PA and streptokinase.

It found that t-PA given concurrently with heparin, and rapidlyinfused within six hours of a heart attack, statistically reduced 30-daymortality by 15 percent over streptokinase.

Put another way, this regimen would save the lives of an additional2,750 patients of the annual 250,000 in the U.S. who suffer an acutemyocardial infarction. That benefit left open the cost-effectiveness ofthe costlier t-PA, which the economic analysis reported in NEJM andJAMA now addresses.

NEJM's authors estimated the cost-effectiveness ratio per year of lifesaved by accelerated t-PA instead of streptokinase at $32,678. Ascardiologist Thomas H. Lee, of Boston's Brigham and Women'sHospital, pointed out in a NEJM editorial: "The study was funded inpart by manufacturers of t-PA [notably Genentech], but similarresults have recently been reported in a study sponsored by amanufacturer of streptokinase."

In the medical care of intractable diseases, "quality of life" is oftenadduced, as opposed to quantity. In assessing GUSTO's clinicaloutcomes, analysts surveyed one-year survivors by telephone. Bothtreatment groups responded, on average, that they would willinglytrade ten years of life at their present state of health for nine years ofexcellent health.

The directors of the overall GUSTO study are cardiologists RobertCaliff at Duke University in Durham, N.C., and Eric Topol of theCleveland Clinic.

Lee himself warned that "Capitated insurance [fee-per-person] willalmost surely punish providers _ when short-term cost-cutting leadsto worse outcomes for patients and higher rates of [hospital]readmission."

In NEJM, the bean-counters pointed out: "The cost-effectiveness oftreatment with accelerated t-PA rather than streptokinase comparesfavorably with that of other therapies whose added medical benefitfor dollars spent is judged by society to be worthwhile."

JAMA dwelt more on contrasting U.S. and foreign patient outcomes.It concluded: "No significant evidence for a differentially greaterbenefit of accelerated t-PA over streptokinase was found in U.S. overnon-U.S. patients. However, increased procedure and treatment usein the United States was associated with only a small decrease inshort-term mortality. Long-term follow-up is required to clarify therelationship between survival and the more intensive U.S.management approach."

Duke's Daniel B. Mark, lead author of the NEJM article, observed:"Up until the last few years, health care providers did not have themotivation to worry about the costs of medical care. They weredealing with society's open checkbook." n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.

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