Activated Clotting Time to Guide Heparin Dosing in Non-ST-Segment-Elevation Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention and Treated With IIb/IIIa Inhibitors: Impact on Ischemic and Bleeding Outcomes: Insights From the TAO Trial

Jean-Guillaume Dillinger; Gregory Ducrocq; Yedid Elbez; Marc Cohen; Christoph Bode; Charles Pollack Jr; José C Nicolau; Patrick Henry; Sasko Kedev; Stephen D Wiviott; Marc S Sabatine; Shamir R Mehta; Philippe Gabriel Steg

doi:10.1161/CIRCINTERVENTIONS.118.006084

Activated Clotting Time to Guide Heparin Dosing in Non-ST-Segment-Elevation Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention and Treated With IIb/IIIa Inhibitors: Impact on Ischemic and Bleeding Outcomes: Insights From the TAO Trial

Circ Cardiovasc Interv. 2018 Jun;11(6):e006084. doi: 10.1161/CIRCINTERVENTIONS.118.006084.

Authors

Affiliations

¹ From the Department of Cardiology, CREATIF, Hôpital Lariboisière, AP-HP, Université Paris Diderot-Sorbonne Paris Cité, Inserm U-942, France (J.-G.D., P.H.).
² FACT (French Alliance for Cardiovascular Trials), an F-CRIN network, DHU FIRE, Hôpital Bichat, AP-HP, Université Paris Diderot-Sorbonne Paris Cité, Inserm U-1148, France (G.D., Y.E., P.G.S.).
³ Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark (M.C.).
⁴ Medizinische Universitatsklinik, Freiburg, Germany (C.B.).
⁵ Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (C.P.).
⁶ Heart Institute (InCor), University of São Paulo Medical School, Brazil (J.C.N.).
⁷ University Clinic of Cardiology, Medical Faculty, University of St. Cyril and Methodius, Skopje, Macedonia (S.K.).
⁸ TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.D.W., M.S.S.).
⁹ McMaster University and the Population Health Research Institute, Hamilton Health Sciences, ON, Canada (S.R.M.).
¹⁰ FACT (French Alliance for Cardiovascular Trials), an F-CRIN network, DHU FIRE, Hôpital Bichat, AP-HP, Université Paris Diderot-Sorbonne Paris Cité, Inserm U-1148, France (G.D., Y.E., P.G.S.) Gabriel.steg@aphp.fr.
¹¹ Royal Brompton Hospital, Imperial College, London, United Kingdom (P.G.S.).

PMID: 29895599
DOI: 10.1161/CIRCINTERVENTIONS.118.006084

Abstract

Background: Monitoring anticoagulation with activated clotting time (ACT) has been proposed to reduce ischemic or bleeding events. However, the value of using ACT to improve outcomes is uncertain. This study sought to determine the relationship between ACT and outcomes during percutaneous coronary intervention in patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) treated by unfractionated heparin with GPIs (glycoprotein IIb/IIIa inhibitors).

Methods and results: From the randomized TAO trial (Treatment of Acute Coronary Syndromes With Otamixaban), we analyzed the value of ACT to predict ischemic and bleeding outcomes in the 3275 patients receiving unfractionated heparin plus eptifibatide. Ischemic and safety outcomes were analyzed according to ACT to determine the best threshold. Median peak ACT was 225 s. There was no correlation (r=-0.02; P=0.24) between the unfractionated heparin dose received and the ACT value before percutaneous coronary intervention. There was no evidence of a nonlinear association between ACT and either ischemic or bleeding events (P=0.66; P=0.07). No threshold was found to predict ischemic complications. Conversely, increased bleeding was observed with ACT >230 s with an optimal threshold of ACTs ≥250 s (4.53% versus 6.17%; odds ratio, 1.46; 95% confidence interval, 1.04-2.06; P=0.028). This optimal threshold varied according to access site: ≥250 s (6.86% versus 10.18%; odds ratio, 1.57; 95% confidence interval, 1.00-2.45; P=0.047) by femoral approach and ≥290 s (2.86% versus 5.43%; odds ratio, 2.24; 95% confidence interval, 1.05-4.44; P=0.027) by radial approach.

Conclusions: In the TAO trial, peak procedural ACT ≥250 s was associated with increased bleeding risk in non-ST-segment-elevation acute coronary syndrome patients treated with unfractionated heparin plus GPIs. This threshold was increased to 290 s when performing radial approach.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01076764.

Keywords: acute coronary syndrome; heparin; myocardial infarction; percutaneous coronary intervention; thrombosis.

Publication types

Comparative Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Acute Coronary Syndrome / blood
Acute Coronary Syndrome / diagnosis
Acute Coronary Syndrome / therapy*
Aged
Anticoagulants / administration & dosage
Anticoagulants / adverse effects*
Blood Coagulation / drug effects*
Cyclic N-Oxides / administration & dosage
Cyclic N-Oxides / adverse effects
Drug Dosage Calculations
Drug Monitoring / methods*
Eptifibatide / administration & dosage
Eptifibatide / adverse effects*
Factor Xa Inhibitors / administration & dosage
Factor Xa Inhibitors / adverse effects
Female
Hemorrhage / chemically induced*
Heparin / administration & dosage
Heparin / adverse effects*
Humans
Male
Middle Aged
Non-ST Elevated Myocardial Infarction / blood
Non-ST Elevated Myocardial Infarction / diagnosis
Non-ST Elevated Myocardial Infarction / therapy*
Percutaneous Coronary Intervention* / adverse effects
Platelet Aggregation Inhibitors / administration & dosage
Platelet Aggregation Inhibitors / adverse effects*
Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
Predictive Value of Tests
Pyridines / administration & dosage
Pyridines / adverse effects
Risk Factors
Time Factors
Treatment Outcome
Whole Blood Coagulation Time*

Substances

Anticoagulants
Cyclic N-Oxides
Factor Xa Inhibitors
Platelet Aggregation Inhibitors
Platelet Glycoprotein GPIIb-IIIa Complex
Pyridines
Heparin
Eptifibatide
otamixaban

Associated data

ClinicalTrials.gov/NCT01076764