Thrombolysis in myocardial infarction (TIMI): update 1987

The "Thrombolysis in Myocardial Infarction" (TIMI) Trial, sponsored by the National Heart, Lung and Blood Institute, has evaluated the efficacy of coronary recanalization in acute myocardial infarction in different phases. TIMI Phase I compared the efficacy of recombinant tissue-type plasminogen activator (rt-PA) with that of streptokinase (SK) in a randomized double blind trial, using 80 mg rt-PA or 1.5 million units SK within 7 hours of clinical onset of infarction. rt-PA recanalized infarct related arteries in 62% compared to 31% with streptokinase. Bleeding complications were similar in both treatment groups and mainly related to vascular puncture sites during heart catheterization. The pharmacological dose of rt-PA, applied, caused a moderate effect on the proteins of the fibrinolytic system, but by far less than streptokinase. TIMI Phase 1.5 compared two preparations of rt-PA, the early formulation in liquid excipient ("old" rt-PA) and the new lyophilized form ("new" rt-PA). With equal dosage regimens of 80 mg, coronary recanalization rates at 90 minutes of infusion were 62% (old rt-PA) and 45% (new rt-PA). The lower recanalization potency of the new rt-PA is related to its shorter plasma half life. Three dosage regimens were evaluated with the new rt-PA, using 80 mg, 100 mg and 150 mg. Coronary recanalization rates were 45%, 71% and 76%, respectively. The dosage of 150 mg achieved the highest recanalization rates at 30 minutes of infusion, 42%. A linear trend test indicated a significant relation (p less than 0.001) between the dose of rt-PA and effects of the proteins of the fibrinolytic system.(ABSTRACT TRUNCATED AT 250 WORDS)