Activated Clotting Time May Predict Ischemic Events in PCI Patients on Heparin Alone

In patients with NSTE-ACS on heparin monotherapy during PCI, lower activated clotting time (ACT) values do not predict bleeding events but do correlate with higher risk of ischemic events, according to a study published online April 14, 2015, ahead of print in Circulation: Cardiovascular Interventions. No such association is seen in patients with planned use of glycoprotein IIb/IIIa inhibitors (GPIs). Take Home: Activated Clotting Time May Predict Ischemic Events in PCI Patients on Heparin Alone

The main FUTURA/OASIS-8 trial consisted of 2,026 high-risk NSTE-ACS patients treated with low-dose fondaparinux who were scheduled for PCI within 72 hours and were randomized to IV heparin at low dose (50 U/kg; n = 1,024) or standard dose (85 U/kg or, with a GPI, 60 U/kg) adjusted for blinded ACT (n = 1,002). There was no difference between the 2 heparin dosing groups for the primary composite endpoint of major or minor bleeding or major vascular access site complications.

For the new study, researchers led by Gregory Ducrocq, MD, of Hôpital Bichat (Paris, France), looked for an association between peak ACT value and outcomes in the 1,882 FUTURA/OASIS-8 patients for whom ACT measurements were available. Testing was done using the Hemochron device (International Technidyne Corporation, Edison, NJ), and peak ACT value was categorized using cutpoints ranging from 200 to 350 seconds in 10-second increments.

Lack of GPI Appears to Fuel Difference

For the cohort as a whole, the cutpoint with the lowest P value for the risk of thrombotic events (death, MI, and TVR) was 220 seconds—patients with an ACT below 220 seconds had an event rate of 7.4% whereas those at or above that value had a rate of 3.2% (adjusted OR 2.42; 95% CI, 1.25-4.39). No linear or nonlinear relationship was found between ACT and outcomes, with the exception of patients who received heparin monotherapy. In that group, a nonlinear relationship between ACT and thrombotic complications was seen (test for curvature P = .042).

Additionally, patients on heparin monotherapy had a higher thrombotic event rate when the ACT was at or below 300 seconds (4.86%) compared with above 300 seconds (2.78%; adjusted OR 1.84; 95% CI 1.06-3.21; P = .03). For the 23.6% of patients with planned use of GPIs, no threshold effect for thrombotic events was observed between 200 and 300 seconds.

No thresholds were seen for bleeding complications regardless of antithrombotic therapy.

“In patients not receiving [GPIs], the target ACT should be greater than 300 seconds because we have demonstrated that it is associated with a lower risk of thrombotic complications without an increased risk of hemorrhagic complications,” the study authors write. They caution that the results cannot be extrapolated to STEMI patients or elective PCI.

Editorial Says ACT Has No ‘Special Role’ in Modern PCI

In an accompanying editorial, Gjin Ndrepepa, MD, and Adnan Kastrati, MD, both of Deutsches Herzzentrum (Munich, Germany), say the study “addresses a highly debatable issue” and “may have clinical applications for the use of ACT to optimize the efficacy of [heparin] dosing during PCI.” However, they caution that the results could be due to “a play of chance” because the analysis was not prespecified, and FUTURA/OASIS-8 was underpowered for bleeding and ischemic complications.

Additionally, Drs. Ndrepepa and Kastrati say the lack of correlation between ACT and bleeding “might have been influenced by the high proportion of patients undergoing PCI via radial approach.” To support this suggestion, they cite an analysis from the EASY trial showing that in patients stented with a transradial approach, greater ACT values did not correlate with an increased risk of bleeding.

Other caveats, they add, are that fondaparinux may distort the relationship between ACT and bleeding or ischemic complications, and that the role of fondaparinux in the setting of PCI for NSTE-ACS “remains poorly defined.” Furthermore, the use of GPIs as a bailout strategy  in 3.3% of patients also may distort the predictive ability of ACT, especially with regard to  ischemic events, since the drugs are typically given to patients considered “at imminent risk of complications (mostly ischemic complications),” Drs. Ndrepepa and Kastrati note.

“Available data including the findings of [this study] do not support ACT measurement during PCI as a reliable predictor of thrombotic or bleeding risk,” they conclude. “This is in line with the 2014 European Society of Cardiology guidelines on myocardial revascularization that do not acknowledge a special role of ACT in the current practice of PCI.”

While acknowledging that the value of ACT to guide heparin dosing in PCI patients is debatable, Dr. Ducrocq and colleagues contend that their findings “confirm the value of ACT guidance in modern NSTE-ACS PCI.”

 


Sources:
1. Ducrocq G, Jolly S, Mehta SR, et al. Activated clotting time and outcomes during percutaneous coronary intervention for non-ST-segment-elevation myocardial infarction: insights from the FUTURA/OASIS-8 trial. Circ Cardiovasc Interv. 2015;Epub ahead of print.
2. Ndrepepa G, Kastrati A. Activated clotting time during percutaneous coronary intervention: a test for all seasons or a mind tranquilizer [editorial]? Circ Cardiovasc Interv. 2015;Epub ahead of print.

Disclosures:

  • FUTURA/OASIS-8 was funded by GlaxoSmithKline.
  • Dr. Ducrocq reports speaker and consulting fees from Astra Zeneca and Lilly.
  • Drs. Ndrepepa and Kastrati report no relevant conflicts of interest. 

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