Relationship between the intensity of heparin anticoagulation and clinical outcomes in patients receiving glycoprotein IIb/IIIa inhibitors during primary percutaneous coronary intervention in acute myocardial infarction

Objectives: We sought to determine the impact of the activated clotting time (ACT) in patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) with unfractionated heparin (UFH) and a glycoprotein IIb/IIIa inhibitor (GPI). Background: UFH+GPI is commonly used during primary PCI for STEMI. UFH anticoagulation is titrated with ACT. Methods: Patients randomized to UFH+GPI in HORIZONS-AMI who underwent primary PCI are included (N = 1,624). Initial UFH bolus was 60 IU kg ^-1 (target ACT: 200-250 sec). Patients were divided into three tertiles of peak ACT (cutoffs 240 and 298 sec). The 30-day rates of major and minor bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE; MACE or major bleeding) were determined. Results: Mortality at 30 days occurred in 2.2, 3.3, and 3.5% of patients in the low to high ACT tertiles, respectively (P_trend = 0.22). Nor was the peak ACT significantly related to major bleeding, MACE or NACE. However, minor bleeding was increased in the highest ACT tertile (14.7% vs. 14.2% vs. 19.4%, P _trend = 0.04). By multivariable analysis peak ACT was not significantly related to major bleeding, mortality, MACE, and NACE but was a significant independent predictor of minor bleeding (odds ratio = 1.027 [1.013, 1.042], P < 0.001, for each 10 sec increase in ACT). Conclusions: In patients undergoing primary PCI for STEMI treated with UFH+GPI, the peak procedural ACT achieved does not have a substantial effect on major bleeding, mortality, or MACE, although lower peak ACT is associated with less minor bleeding.