An independently derived and validated predictive model for selecting patients with myocardial infarction who are likely to benefit from tissue plasminogen activator compared with streptokinase.
BACKGROUND
In the Global Utilization of Streptokinase and tPA for Occluded coronary arteries (GUSTO) trial, patients with myocardial infarction who were treated with tissue plasminogen activator (tPA) had a 6.3% 30-day mortality, compared with a mortality of 7.3% among those treated with streptokinase, despite a greater risk of intracranial hemorrhage with tPA. However, in part because of its higher cost, tPA has not been adopted universally.


METHODS
Using an independently developed model, we predicted the benefits of tPA therapy in the 24,146 patients in the GUSTO trial and compared these predictions with the actual benefits of tPA, after classifying patients by their risks of mortality and intracranial hemorrhage. We also performed a "patient-specific" cost-effectiveness analysis among different strata of expected benefit of tPA.


RESULTS
Our model predicted that among patients with myocardial infarction, 61% of the benefit of tPA use in reducing mortality accrued to only 25% of patients; treating half of patients could capture 85% of the benefit. Including the risk of intracranial hemorrhage, our model predicted that treating half the GUSTO patients with tPA and the others with streptokinase would yield similar outcomes as treating all patients with tPA, because the additional risk of intracranial hemorrhage exceeded the expected benefit in some patients. When patients were stratified into quartiles of risk, the observed outcomes in the GUSTO patients corresponded well with these predicted results. The estimated cost-effectiveness of tPA was sensitive to patient characteristics.


CONCLUSIONS
For selected patients, use of tPA yields substantially better outcomes than streptokinase, and use of the less expensive agent is difficult to justify. For many patients, however, tPA is unlikely to provide any additional benefit and, in some patients, it may even cause net harm.
Division of Clinical Care Research, Department of Medicine, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111, USA. dkent1@lifespan.org
David M
DM
Kent
Rodney A
RA
Hayward
John L
JL
Griffith
Sandeep
S
Vijan
Joni R
JR
Beshansky
Robert M
RM
Califf
Harry P
HP
Selker
D000328:Adult; D000367:Age Factors; D003362:Cost-Benefit Analysis; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018803:Models, Economic; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D018579:Patient Selection; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012307:Risk Factors; D012737:Sex Factors; D013300:Streptokinase / Q000191:economics / Q000627:therapeutic use*; D016019:Survival Analysis; D015912:Thrombolytic Therapy / Q000191:economics / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000191:economics / Q000627:therapeutic use*; D016896:Treatment Outcome
D013300:Streptokinase; D010959:Tissue Plasminogen Activator