Relationship between activated clotting time and ischemic or hemorrhagic complications - Analysis of 4 recent randomized clinical trials of percutaneous coronary intervention

Background - Unfractionated heparin (UFH) is the most widely used antithrombin during percutaneous coronary intervention (PCI). Despite significant pharmacological and mechanical advancements in PCI, uncertainty remains about the optimal activated clotting time ( ACT) for prevention of ischemic or hemorrhagic complications. Methods and Results - We analyzed the outcome of all UFH-treated patients enrolled in 4 large, contemporary PCI trials with independent adjudication of ischemic and bleeding events. Of 9974 eligible patients, maximum ACT was available in 8369 (84%). The median ACT was 297 seconds (interquartile range 256 to 348 seconds). The incidence of death, myocardial infarction, or revascularization at 48 hours, by ACT quartile, was 6.2%, 6.8%, 6.0%, and 5.7%, respectively ( P = 0.40 for trend). Covariate-adjusted rate of ischemic complications was not correlated with maximal procedural ACT ( continuous value, P = 0.29). Higher doses of UFH ( > 5000 U, or up to 90 U/kg) were independently associated with higher rates of events. The incidence of major or minor bleeding at 48 hours, by ACT quartile, was 2.9%, 3.5%, 3.8%, and 4.0%, respectively ( P = 0.04 for trend). In a multivariable logistic model with a spline transformation for ACT, there was a linear increase in risk of bleeding as the ACT approached 365 seconds ( P = 0.01), which leveled off beyond that value. Increasing UFH weight-indexed dose was independently associated with higher bleeding rates (OR 1.04 [1.02 to 1.07] for each 10 U/kg, P = 0.001). Conclusions - In patients undergoing PCI with frequent stent and potent platelet inhibition use, ACT does not correlate with ischemic complications and has a modest association with bleeding complications, driven mainly by minor bleeding. Lower values do not appear to compromise efficacy while increasing safety.