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COMBINATION HALF-DOSE TPA AND STREPTOKINASE ACHIEVES HIGHER PATENCY

Executive Summary

COMBINATION HALF-DOSE TPA AND STREPTOKINASE ACHIEVES HIGHER PATENCY at lower cost than full-dose tissue plasminogen activator, researcher Cindy Grines, MD, University of Kentucky, told the American College of Cardiology annual meeting in New Orleans March 19. "Compared to full-dose, commercially available TPA, the combination of half-dose TPA with streptokinase offers superior acute patency rates, a trend for lower reocclusion, improved clinical outcome, similar prevalence of severity of bleeding complications, and a substantial reduction in cost," Grines reported. In the 208-patient study, the Kentucky Acute Myocardial Infarction Trial (KAMIT), a regimen of 50 mg TPA (10 mg, followed by 40 mg over 60 minutes) and 1.5 mil. units of streptokinase over one hour was compared to full-dose TPA (100 mg). Patients were treated within six hours of the first symptoms of acute myocardial infarction. Grines reported that 78% of patients receiving the TPA/streptokinase combination demonstrated vessel patency at 90 minutes after initiation of therapy compared to 58% of patients receiving full-dose TPA. Since it has been suggested that early streptokinase treatment increases patency, Grines said, a subgroup analysis was conducted of patients who received therapy in the first three hours following acute myocardial infarction. The patency rate in that group was 88% for the combination versus 51% for TPA alone. Patency at three to six hours was equal between the two groups at 67%. Early reocclusion, which has been a problem with TPA because of its short half-life, was reduced from 10% in the TPA group to 3% with the TPA/streptokinase therapy. Recurrent unstable ischemia occurred in 9% of patients in the combination arm compared to 15% in the TPA cohort, necessitating urgent catherization for 7% of patients treated with combination therapy compared to 10% of TPA-treated patients. "Reinfarction occurred more frequently in the TPA arm as well as the need for emergency coronary artery bypass," Grines noted. Reinfarction occurred in 3% of the TPA group and did not occur in the TPA/streptokinase group. * Using prices derived from the University of Kentucky pharmacy logs, Grines described the cost savings expected when using the combination therapy versus full-dose TPA. Noting that the cost of 100 mg of TPA to the pharmacy is $2,300 and $3,200 to the patient, and the cost of streptokinase is $87 to the pharmacy and $122 to the patient, Grines commented that "our regimen of half-dose TPA was effective yet resulted in a cost of$1,230 to the pharmacy and $1,720 to the patient, or approximately half of the cost of TPA therapy." Clinical outcome was improved in the TPA/streptokinase arm compared to TPA alone. "An event-free hospital stay occurred in 84% of patients with combination thrombolytic therapy compared to 74% after full-dose TPA," Grines remarked. However, overall mortality was not greater for the combination therapy with regard to TPA, 6% versus 4%, respectively. The prevalence and severity of bleeding was not reduced by the combination therapy, with serious bleeding occurring in 12% of TPA/streptokinase patients and 11% in the TPA group.
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