Antifibrinolytic therapy: evidence, bias, confounding (and politics!)

Cardiac surgery can be complicated by postoperative bleeding and a need for blood transfusion and surgical reexploration. Anti-fibrinolytic drugs such as aprotinin and tranexamic acid may reduce bleeding risks but could possibly increase thrombotic complications. Aprotinin, in particular, has recently been implicated in at least two large observational studies, but this could be because it is more widely used in high-risk cardiac surgical patients. Observational studies are prone to several important sources of bias, in particular, confounding by indication (high-risk patients are more likely to receive aprotinin and more likely to have postoperative complications, irrespective of their exposure to aprotinin). Although multivariate adjustment and propensity score-matching can adjust for confounding, there is no certainty that it removes all such bias. For all anti-fibrinolytic drugs, it remains unclear as to whether the beneficial effect on reduced bleeding outweighs a possible increased risk of thrombotic complications. Debate will continue until we have the results of definitive large randomized trials powered to detect a clinically important effect on outcome.