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Defining optimal activated clotting time for percutaneous coronary intervention: A systematic review and Bayesian
Salvatore Mottillo1,2,3, Kristian B Filion1,2,4, Lawrence Joseph2,5
1Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital/McGill University, Montreal, Quebec, Canada.
Insights
The optimal activated clotting time (ACT) for unfractionated heparin (UFH) during percutaneous coronary intervention (PCI) remains unclear. This study found inconsistent associations between peak ACT and major adverse cardiac or bleeding events, highlighting the need for further research.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Current guidelines recommend monitoring unfractionated heparin (UFH) with activated clotting time (ACT) during percutaneous coronary intervention (PCI).
- However, the ideal ACT threshold for optimal patient outcomes during PCI is not well-defined.
Purpose of the Study:
- To investigate the relationship between peak ACT levels during PCI and subsequent 30-day major adverse cardiac events (MACE) and bleeding.
- To analyze data from randomized controlled trials (RCTs) evaluating UFH use in PCI patients.
Main Methods:
- A systematic literature search was conducted across major databases (Cochrane, EMBASE, Medline) for RCTs published up to May 2015.
- Bayesian meta-regression was employed to analyze data from 13 RCTs (n=17,455) involving patients treated with UFH alone or UFH plus a glycoprotein IIb/IIIa inhibitor (GPI).
Main Results:
- In patients receiving UFH alone, the probability of MACE was similar for peak ACTs of 200 sec (7.0%) and 300 sec (5.8%).
- In patients receiving UFH with a GPI, MACE probability was lower at a peak ACT of 200 sec (2.8%) compared to 300 sec (7.2%).
- The association between peak ACT values and MACE or major bleeding was inconsistent across individual RCTs.
Conclusions:
- The current meta-regression analysis did not yield conclusive results regarding the optimal peak ACT for UFH during PCI.
- Further large-scale RCTs are necessary to directly compare low versus high UFH doses and establish definitive ACT targets.
Background:
Guidelines recommend routine monitoring of unfractionated heparin (UFH) with activated clotting time (ACT) during percutaneous coronary intervention (PCI). However, the optimal ACT for patients undergoing PCI is unclear.
Methods:
We sought to determine the association of peak ACT during PCI with 30-day major adverse cardiac events (MACE; all-cause mortality, myocardial infarction, and revascularization) and bleeding events. We searched the Cochrane Central Register of Controlled Trials, EMBASE, and Medline for randomized controlled trials (RCTs) evaluating UFH through May 2015. Only patients randomized to UFH alone or to UFH with a glycoprotein IIb/IIIa inhibitor (GPI) were analyzed using Bayesian meta-regression.
Results:
Among 13 included RCTs (n = 17455), eight (n = 5521) included study arms of UFH alone and 12 (n = 11934) included arms of UFH with a GPI. Peak ACT ranged from 201 to 460 sec for UFH alone and 248-317 sec for UFH with a GPI. With UFH alone, the probability of MACE was 7.0% (95% credible interval [CrI] 1.5, 31.5) for a peak ACT of 200 sec and 5.8% (95% CrI 2.6, 12.0) for 300 sec. Among UFH with a GPI, the probability of MACE was 2.8% (95% CrI 0.8, 6.8) for a peak ACT of 200 sec and 7.2% (95% CrI 5.4, 9.7) for 300 sec.
Conclusion:
Among individual RCTs, the probability of MACE and major bleeding events associated with low versus high values of peak ACT is inconsistent. Our meta-regression results are inconclusive, emphasizing the need for RCTs comparing low versus high doses of UFH. © 2016 Wiley Periodicals, Inc.
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