Heparin dosing and outcome in acute coronary syndromes: The GUSTO-IIb experience

Background This study analyzed relationships among heparin dosage, patient characteristics, and 30-day outcome because optimal unfractionated-heparin dosing in acute coronary syndromes remains uncertain. Methods Patients (n = 5335) randomized to heparin therapy in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb trial were studied. The heparin dose was adjusted to a target activated partial thromboplastin time (aPIT) and normalized for the patient's weight. Mortality and cardiac (re)infarction within 30 days and their association with patient characteristics and heparin dosing were evaluated. Results The lowest mortality rate appeared with a heparin dose of approximately 14 U/kg/h or an aPTT of approximately 70 seconds. Heparin dosing was a significant predictor of outcome after adjusting for presenting coronary syndrome; a trend remained after adjusting for other baseline differences. This association was lost when adjusted for the aPTT result. Patients who died early appeared to have lower heparin dosing than those with later mortality (P =.012). Heparin "resistance" with relatively high heparin dosages and low aPTT values did not increase the risk for adverse outcome. Conclusions There is a defined, dose-associated benefit of unfractionated heparin in acute coronary syndromes similar to that seen previously in thrombolytic-treated infarctions. Heparin therapy is complicated by its complex biologic interactions and relatively crude measures of its effect. Better measures of heparin effectiveness and strategies need to be developed with either better antithrombin agents or adjunctive therapies such as antiplatelet regimens to treat patients who require benefits beyond that supplied by unfractionated heparin.