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on August 9, 2004

A more recent version of this article appeared on August 24, 2004

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Submitted on December 16, 2003
Revised on April 20, 2004
Accepted on April 21, 2004

Relationship Between Activated Clotting Time and Ischemic or Hemorrhagic Complications. Analysis of 4 Recent Randomized Clinical Trials of Percutaneous Coronary Intervention

Sorin J. Brener MD^*, David J. Moliterno MD, A. Michael Lincoff MD, Steven R. Steinhubl MD, Kathy E. Wolski MS, and Eric J. Topol MD

From the Department of Cardiovascular Medicine (S.J.B., A.M.L., K.E.W., E.J.T.), Cleveland Clinic Foundation, Cleveland, Ohio, and Divisions of Cardiology, University of Kentucky (D.J.M.), Lexington, Ky, and University of North Carolina (S.R.S.), Chapel Hill, NC.

^* To whom correspondence should be addressed. E-mail: breners{at}ccf.org.

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.

Key words: angioplasty • heparin • ischemia • hemorrhage

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