What is the clinical evidence from this study?

Study design: Observational. Population: Percutaneous coronary intervention (n=8369). Intervention: Activated clotting time (ACT) vs. Lower ACT values. Primary outcome: Death, myocardial infarction, or revascularization at 48 hours (p=0.40 for trend).

August 10, 2004Open Access

Relationship Between Activated Clotting Time and Ischemic or Hemorrhagic Complications

Key Result

Maximal activated clotting time during PCI did not correlate with ischemic complications (P=0.40 for trend) but showed a linear increase in bleeding risk as ACT approached 365 seconds (P=0.01).

Study Design

Type

Observational (n=8,369)

Multicenter

Yes

Structured PICO

Does higher activated clotting time (ACT) reduce ischemic complications or increase bleeding in patients undergoing PCI with unfractionated heparin?

Population

8,369 patients undergoing percutaneous coronary intervention treated with unfractionated heparin, evaluated for ischemic and bleeding complications at 48 hours.

Exposure

Higher activated clotting time (ACT) levels achieved with unfractionated heparin (UFH)

Comparator

Lower activated clotting time (ACT) levels

Outcome

Composite of death, myocardial infarction, or revascularization at 48 hourscomposite

In patients undergoing PCI, higher ACT values do not reduce ischemic complications but are associated with increased bleeding risk, suggesting lower ACT targets may improve safety without compromising efficacy.

Main Result

p-value: p=0.40 for trend

Abstract

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.