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ISIS-3
Third International Study of Infarct Survival
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Author(s) |
ISIS-3 (Third International Study of Infarct Survival) collaborative group
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Title(s) |
ISIS-3: a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41 299 cases of suspected acute myocardial infarction
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Reference(s) |
Lancet 1992;339:753-70
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Disease |
AMI
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Purpose |
To compare the 3 clot-dissolving drugs rt-PA and plasminogen streptokinase activator complex (APSAC), and to compare heparin plus aspirin with aspirin alone in patients with definite or suspected AMI
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Study design |
Randomised, double-blind, parallel-group, factorial
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Follow-up |
6 months
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Patients |
41,299 patients (13,780 streptokinase, 13,746 rt-PA and 13,773 APSAC; 20,643 aspirin alone and 20,656 aspirin plus heparin). Time since onset of symptoms: ≤ 24 h
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Treatment regimen |
Streptokinase, 1.5 x 106 U iv over 1 h, rt-PA, 0.6 x 106 U/kg iv over 4 h, or APSAC, 30 U iv over 3 min. All patients received aspirin, 162.5 mg/day, or aspirin (same dose) plus heparin, 12,500 U bid sc for 7 days
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Results |
The addition of heparin to aspirin was associated with an excess of major non-cerebral bleeds and with definite or probable cerebral haemorrhage, but there was no significant difference with respect to total stroke. During the heparin treatment period, there were slightly fewer deaths in the aspirin plus heparin group. Some of this early benefit may, however, be lost when heparin treatment ceases; no significant mortality advantage was observed in days 0-35 or during 2 months’ follow-up. There was a greater number of reports of allergy and a slight excess of strokes, with much of this excess attributed to cerebral haemorrhage in the APSAC group compared to the streptokinase group. There was no significant difference between the two groups in the rate of reinfarction or mortality during days 0-35. The survival rate after 6 months was also similar in the 2 groups. There was a significant excess of strokes in the rt-PA group compared to the streptokinase group, many of which were reported soon after treatment started and were attributed to cerebral haemorrhage. Fewer reinfarctions were observed in the rt-PA group than in the streptokinase group. There was no significant difference in mortality between day 0 and day 35 and no difference in 6-month survival between the streptokinase and rt-PA groups
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