A Cochrane review [Abstract] 1 included 20 studies with a total of 3 458 subjects. All trials combined, AT III did not statistically significantly reduce overall mortality compared with the control group (RR 0.96, 95% CI 0.89 to 1.03). A total of 32 subgroup and sensitivity analyses were carried out. Analyses based on risk of bias, different populations, and the role of adjuvant heparin gave insignificant differences. AT III reduced the multiorgan failure score among survivors in an analysis involving very few patients. AT III increased bleeding events (RR 1.52, 95% CI 1.30 to 1.78).
Comment: The quality of evidence is downgraded by imprecise results (few patients and wide confidence intervals). A potentially beneficial effect of AT III must be modest compared to what had been expected. There is sufficient evidence to reject a beneficial effect of more than 10% RRR (5% absolute risk reduction) on mortality and there is still the possibility that use of AT III may be harmful by means of increased bleeding.
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