Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2.ISIS-2 (Second International Study of Infarct Survival) Collaborative Group.

17,187 patients entering 417 hospitals up to 24 h (median 5 h) after the onset of suspected acute myocardial infarction were randomized, with placebo control, between i) a 1 h intravenous infusion of 1.5 million units of streptokinase; ii) 1 month of 160 mg/day enteric-coated aspirin; iii) both active treatments; or iv) neither. Streptokinase alone and aspirin alone each produced a highly significant reduction in 5 week vascular mortality: 791/8592 (9.2%) vascular deaths among patients allocated streptokinase infusion versus 1029/8595 (12.0%) among those allocated placebo infusion (odds reduction: 25% +/- 4; 2p less than 0.00001); 804/8587 (9.4%) vascular deaths among patients allocated aspirin tablets versus 1016/8600 (11.8%) among those allocated placebo tablets (odds reduction: 23% +/- 4; 2p less than 0.00001). The combination of streptokinase and aspirin was significantly (2p less than 0.0001) better than either agent alone. Their separate effects on vascular death appeared to be additive: 343/4292 (8.0%) among patients allocated both active agents versus 568/4300 (13.2%) among those allocated neither (odds reduction: 42% +/- 5; 95% confidence limits 34% to 50%). There was evidence of benefit rom each agent even for patients treated late after pain onset (odds reduction at 0-4, 5-12, and 13-24 h: 35% +/- 6, 16% +/- 7 and 21% +/- 12 for streptokinase alone; 25% +/- 7,21% +/- 7 and 21% +/- 12 for aspirin alone; and 53% +/- 8,32% +/- 9 and 38% +/- 15 for the combination of streptokinase and aspirin). Streptokinase was associated with an excess of bleeds requiring transfusion (0.5% versus 0.2%) and of confirmed cerebral hemorrhage (0.1% versus 0.0%), but with fewer other strokes (0.6% versus 0.8%). These "other" strokes may have included a few undiagnosed cerebral hemorrhages, but still there was no increase in total strokes (0.7% streptokinase versus 0.8% placebo infusion). Aspirin significantly reduced nonfatal reinfarction (1.0% versus 2.0%) and nonfatal stroke (0.3% versus 0.6%), and was not associated with any significant increase in cerebral hemorrhage or in bleeds requiring transfusion. An excess of nonfatal reinfarction was reported when streptokinase was used alone, but this appeared to be entirely avoided by the addition of aspirin. Those allocated the combination of streptokinase and aspirin had significantly fewer reinfarctions (1.8% versus 2.9%), strokes (0.6% versus 1.1%), and deaths (8.0% versus 13.2%) than those allocated neither.(ABSTRACT TRUNCATED AT 250 WORDS)

RCT Entities:   Population Interventions Outcomes