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Original Investigation
February 2017

Evaluation of Ischemic and Bleeding Risks Associated With 2 Parenteral Antiplatelet Strategies Comparing Cangrelor With Glycoprotein IIb/IIIa InhibitorsAn Exploratory Analysis From the CHAMPION Trials

Author Affiliations
  • 1Brigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts
  • 2Department of Medicine, Stanford University Medical School, Stanford, California
  • 3Deputy Editor, JAMA Cardiology
  • 4Columbia University Medical Center and the Cardiovascular Research Foundation, New York, New York
  • 5The Medicines Company, Parsippany, New Jersey
  • 6French Alliance for Cardiovascular Clinical Trials, Départements Hospitalo-Universitaires Fibrosis, Inflammation, Remodeling, Institut National de la Santé et de la Recherche Médicale, Paris, France
  • 7Hôpital Bichat, Assistance-Publique–Hôpitaux de Paris, Paris, France
  • 8National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, England
  • 9Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
  • 10Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany
  • 11Scripps Clinic and Scripps Translational Science Institute, La Jolla, California
  • 12Azienda Ospedaliero-Universitaria di Parma, Province of Parma, Italy
  • 13Green Lane Cardiovascular Service, Auckland, New Zealand
JAMA Cardiol. 2017;2(2):127-135. doi:10.1001/jamacardio.2016.4556
Key Points

Question  What are the relative ischemic and bleeding risks associated with glycoprotein IIb/IIIa inhibitors and more potent P2Y12 antagonists, such as cangrelor, in patients undergoing percutaneous coronary intervention?

Findings  In this exploratory analysis of pooled patient-level data from the 3 Cangrelor vs Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION) trials including 12 140 patients, cangrelor alone was associated with similar ischemic risk and lower risk-adjusted severe bleeding risk compared with clopidogrel given with glycoprotein IIb/IIIa inhibitors.

Meaning  Cangrelor may offer an alternative potent, parenteral strategy to glycoprotein IIb/IIIa inhibitors with a favorable bleeding profile in percutaneous coronary intervention.

Abstract

Importance  In the context of contemporary pharmacotherapy, optimal antiplatelet management with percutaneous coronary intervention (PCI) has not been well established.

Objective  To compare the ischemic and bleeding risks associated with glycoprotein IIb/IIIa inhibitors (GPIs) and a potent P2Y12 antagonist, cangrelor, in patients undergoing PCI.

Design, Setting, and Participants  An exploratory analysis of pooled patient-level data from the 3 phase 3 Cangrelor vs Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION PCI, CHAMPION PLATFORM, and CHAMPION PHOENIX) trials of patients undergoing elective or nonelective PCI. The participants included 10 929 patients assigned to cangrelor but not receiving GPIs (cangrelor alone) and 1211 patients assigned to clopidogrel (or placebo) and receiving routine GPIs (clopidogrel-GPI). Patients requiring bailout or rescue GPI therapy were excluded. To account for risk imbalances, 1:1 propensity score matching based on 16 baseline clinical variables yielded 1021 unique matched pairs. The present study’s data analysis was conducted from October 28, 2015, to August 6, 2016.

Main Outcomes and Measures  The primary efficacy end point was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours. Safety was assessed by 3 validated bleeding scales (Global Use of Strategies to Open Occluded Coronary Arteries [GUSTO], Thrombolysis in Myocardial Infarction [TIMI], and Acute Catheterization and Urgent Intervention Triage) and requirement for blood transfusions.

Results  Of the 12 140 patients included in the analysis, 8779 were men (72.3%), and the mean (SD) age was 63.2 (11.3) years. Patients in the clopidogrel-GPI group were more likely to be male (75.6% vs 71.9%), younger (median, 60 [range, 23-91] years vs 64 [range, 26-95] years), enrolled from the United States (77.9% vs 40.0%), and present with an acute coronary syndrome, but they had lower comorbid disease burden and were less likely to receive bivalirudin (8.8% vs 27.3%). In the matched cohorts, the rates of the primary efficacy end point were not significantly different between the cangrelor alone and clopidogrel-GPI groups (2.6% vs 3.3%; odds ratio [OR], 0.79; 95% CI, 0.48-1.32). There was a nonsignificant trend toward lower rates of GUSTO-defined severe/life-threatening bleeding with cangrelor alone compared with clopidogrel-GPI (0.3% vs 0.7%; OR, 0.43; 95% CI, 0.11-1.66). Rates of TIMI-defined major or minor bleeding were significantly lower in patients treated with cangrelor alone (0.7% vs 2.4%; OR, 0.29; 95% CI, 0.13-0.68).

Conclusions and Relevance  Based on a pooled analysis from the 3 phase 3 CHAMPION trials, cangrelor alone was associated with similar ischemic risk and lower risk-adjusted bleeding risk compared with clopidogrel-GPIs.

Trial Registration  clinicaltrials.gov Identifiers: NCT00305162, NCT00385138, and NCT01156571

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