ISIS -2
ISIS -2
Randomised Trial of IV Streptokinase, Oral ASA, both or either among 17,187 cases of suspected acute MI
ISIS-2 (Second International Studay of Infarct Survival)
The Lancet, 1988 2 (8607): 349-60
History:
-One of the first randomized trials involving thousands of patients
-GISSI trial 2 years earlier had shown mortality benefit of fibrinolytic therapy, but timing not established
-ASA had been shown to be of benefit post MI for secondary prevention, but only one other small rand trial had been done in setting of acute MI.
Goals:
-Determine “time window” for benefit of fibrinolytics and
-Determine benefit of ASA in setting of acute MI.
Methods:
-Randomized, Placebo controlled Trial
-417 hospitals, 16 countries, randomized 17,187 patients
-Inclusion: Thought within 24 hours of onset of sx of suspected MI, EKG changes not inc. criteria
-Exclusion: h/o CVA, GIB, recent severe trauma, severe persistent HTN, med allergy
-2x2 Factorial Study:
4300 Placebo
4295 ASA (160mg x 1 month) alone
4300 Streptokinase (1.5mU over 1h) alone
4292 ASA + Streptokinase
-Primary Outcome: Very simply 30day mortality at 5 weeks
-Followup was excellent: All but 206 pts., 97% to week 5 and 96% to end of study
Results in 5-week mortality:
1. SK vs. Placebo – 791 (9.2%) deaths vs. 1029 (12.0%), 25% reduction mortality
-subgroup analysis showed reduction larger in pts received SK w/in 4 hrs
-however, reduction still significant even at 24 hrs
-major bleeds more common 0.5% vs. 0.2%
-CVA also more common 0.1% vs. 0
2. ASA vs. Placebo – 804 (9.4%) deaths vs. 1016 (11.8%), 23% reduction mort.
-no major increase in major bleeds or CVAs
3. SK + ASA vs. neither: 8.0% vs. 13.2 %, 42% reduction mort.
Conclusions
-Although the earlier the thrombolysis, the more mortality benefit, still see reduction in mortality at 24h.
-Mortality benefit of ASA and fibrinolytics appear to be additive.
-Optimum dose of ASA in acute MI never established.
-At a dose of 160mg, ASA had no increased risk of bleeding
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