American Society of Hirudotherapy

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

Meta-analysis published in Circulation (2004)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Meta-analysisClinical TrialsBrener SJ · Circulation, 2004

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.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Publication typeJournal ArticleMeta-Analysis
Indexed MeSH termsAbciximabAgedAngioplasty, Balloon, CoronaryAntibodies, MonoclonalAnticoagulantsAspirinBlood Coagulation TestsClopidogrelComorbidityCoronary RestenosisDouble-Blind MethodDrug Synergism

Summary

Unfractionated heparin (UFH) is the most widely used antithrombin during percutaneous coronary intervention (PCI).

Why This Matters for Hirudotherapy

This study analyzed outcomes of 8,369 evaluable patients treated with unfractionated heparin (UFH) across four percutaneous coronary intervention (PCI) trials to assess the relationship between activated clotting time (ACT) and ischemic or hemorrhagic complications. The analysis found no correlation between maximal procedural ACT and ischemic complications (P=0.29) and only a modest association with bleeding—primarily minor—that increased linearly up to 365 seconds. Higher UFH doses were independently associated with both higher event and bleeding rates. This study does not mention hirudin, leeches, hirudotherapy, or any leech-derived compounds anywhere in the abstract. Consequently, this article has no direct relevance to ASH's domain of hirudotherapy or the leech secretome; it pertains solely to heparin dosing and ACT monitoring during PCI.

Citation

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

Brener SJ · Circulation, 2004

Added to ASH library: May 27, 2026 · Site last updated: June 18, 2026

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