RELATION OF REPERFUSION SUCCESS WITH ANISTREPLASE OR ALTEPLASE IN ACUTE MYOCARDIAL-INFARCTION TO BODY-WEIGHT

Adjustment in dose based on body size is not recommended currently for thrombolytic regimens, except for a reduction in alteplase (recombinant tissue-type plasminogen activator [rt-PA]) dose for safety reasons in patients with low body weight. It is unresolved how to dose thrombolytic scents in very heavy patients. The study objective was to assess whether patency of the infarct-related artery at 1 day after therapy with anistreplase (anisoylated plasminogen streptokinase as activator complex [APSAC]) or rt-PA is adversely affected by increased body weight. Data were analyzed from a double-blind, randomized, comparative study of APSAC (30 U/5 min) versus rt-PA (100 mg/3 hours, adjusted downward for body weight <65 kg), together with heparin and aspirin, in patients with acute myocardial infarction presenting within 4 hours of symptom onset. Coronary patency, determined at 1 day, was assessed in a blinded fashion, and patency success was correlated with body weight, divided into quintiles. In patients treated with APSAC, coronary patency rates were similar in those in the upper quintile of body weight (>94 kg; n = 22) and in the low-normal weight group (n = 126) (86 and 90%, respectively, for perfusion grade 2/3 [p = 0.64]; and 82 and 74%, respectively, for grade 3 [p = 0.42]). In contrast, for the rt-PA group, heavy patients (n = 34) achieved significantly lower patency rates (74 vs 89% for grade 2/3 [p = 0.02]; and 59 vs 77% for grade 3 [p = 0.03]). The dose of heparin administered, adjusted to maintain a therapeutic partial thromboplastin time until the 1-day (mean 28 hours) angiogram, was greater in the heavy than in the low-normal weight group (mean +/- SE 39,680 +/- 4,818 vs 30,027 +/- 1,177 U; p = 0.007). Thus, coronary artery patency rates at 1 day are not adversely affected in heavy who receive standard doses of APSAC, but are lower after standard doses of rt-PA, suggesting that larger doses of rt-PA or heparin, or both, may be needed to achieve an optimal patency outcome.