Cangrelor With and Without Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Percutaneous Coronary Intervention

on behalf of the, CHAMPION Investigators, CHAMPION Investigators

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background Cangrelor, an intravenous, reversible P2Y12 antagonist, is approved for use in patients undergoing percutaneous coronary intervention (PCI). Objectives This study sought to evaluate the efficacy and safety of cangrelor compared with clopidogrel in subgroups that did and did not receive glycoprotein IIb/IIIa inhibitors (GPIs). Methods This pooled, patient-level analysis of the 3 CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials analyzed all randomized patients who underwent PCI and received the study drug (n = 24,902). Only bailout/rescue GPI use was permitted, except in CHAMPION PCI, in which routine or bailout/rescue GPI use was at the site investigator's discretion. The primary efficacy endpoint was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h after randomization. Results Overall, 3,173 patients (12.7%) received a GPI, most commonly eptifibatide (69.4%). Despite variation in indications for GPIs, baseline characteristics were well balanced between the cangrelor and clopidogrel arms in subsets receiving and not receiving GPIs. Rates of the primary composite endpoint were lower with cangrelor compared with clopidogrel in patients who did (4.9% vs. 6.5%; odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.55 to 1.01) or did not receive a GPI (3.6% vs. 4.4%; OR: 0.82; 95% CI: 0.72 to 0.94; Pint = 0.55). Cangrelor did not increase the primary safety endpoint, GUSTO-defined severe/life-threatening bleeding, in patients who did (0.4% vs. 0.5%; OR: 0.71; 95% CI: 0.25 to 1.99) or did not receive GPIs (0.2% vs. 0.1%; OR: 1.56; 95% CI: 0.80 to 3.04; Pint = 0.21). GPI use was associated with increased risk of bleeding in both treatment arms. Conclusions Cangrelor's efficacy in reducing ischemic complications in patients undergoing PCI was maintained irrespective of GPI administration. GPI use was associated with substantially higher bleeding rates, regardless of the randomization to cangrelor or clopidogrel. (A Clinical Trial to Demonstrate the Efficacy of Cangrelor [PCI]: NCT00305162; Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition [PLATFORM]: NCT00385138; A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]: NCT01156571)

Original languageEnglish (US)
Pages (from-to)176-185
Number of pages10
JournalJournal of the American College of Cardiology
Volume69
Issue number2
DOIs
StatePublished - Jan 17 2017

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Platelet Glycoprotein GPIIb-IIIa Complex
clopidogrel
Percutaneous Coronary Intervention
Odds Ratio
Confidence Intervals
Hemorrhage
Random Allocation
cangrelor
Blood Platelets
Safety
Therapeutics
Stents
Myocardial Ischemia
Thrombosis
Myocardial Infarction
Research Personnel
Clinical Trials

Keywords

  • antiplatelet therapy
  • bleeding
  • coronary artery disease
  • outcomes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Cangrelor With and Without Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Percutaneous Coronary Intervention. / on behalf of the; CHAMPION Investigators; CHAMPION Investigators.

In: Journal of the American College of Cardiology, Vol. 69, No. 2, 17.01.2017, p. 176-185.

Research output: Contribution to journalArticle

on behalf of the ; CHAMPION Investigators ; CHAMPION Investigators. / Cangrelor With and Without Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Percutaneous Coronary Intervention. In: Journal of the American College of Cardiology. 2017 ; Vol. 69, No. 2. pp. 176-185.
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title = "Cangrelor With and Without Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Percutaneous Coronary Intervention",
abstract = "Background Cangrelor, an intravenous, reversible P2Y12 antagonist, is approved for use in patients undergoing percutaneous coronary intervention (PCI). Objectives This study sought to evaluate the efficacy and safety of cangrelor compared with clopidogrel in subgroups that did and did not receive glycoprotein IIb/IIIa inhibitors (GPIs). Methods This pooled, patient-level analysis of the 3 CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials analyzed all randomized patients who underwent PCI and received the study drug (n = 24,902). Only bailout/rescue GPI use was permitted, except in CHAMPION PCI, in which routine or bailout/rescue GPI use was at the site investigator's discretion. The primary efficacy endpoint was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h after randomization. Results Overall, 3,173 patients (12.7{\%}) received a GPI, most commonly eptifibatide (69.4{\%}). Despite variation in indications for GPIs, baseline characteristics were well balanced between the cangrelor and clopidogrel arms in subsets receiving and not receiving GPIs. Rates of the primary composite endpoint were lower with cangrelor compared with clopidogrel in patients who did (4.9{\%} vs. 6.5{\%}; odds ratio [OR]: 0.74; 95{\%} confidence interval [CI]: 0.55 to 1.01) or did not receive a GPI (3.6{\%} vs. 4.4{\%}; OR: 0.82; 95{\%} CI: 0.72 to 0.94; Pint = 0.55). Cangrelor did not increase the primary safety endpoint, GUSTO-defined severe/life-threatening bleeding, in patients who did (0.4{\%} vs. 0.5{\%}; OR: 0.71; 95{\%} CI: 0.25 to 1.99) or did not receive GPIs (0.2{\%} vs. 0.1{\%}; OR: 1.56; 95{\%} CI: 0.80 to 3.04; Pint = 0.21). GPI use was associated with increased risk of bleeding in both treatment arms. Conclusions Cangrelor's efficacy in reducing ischemic complications in patients undergoing PCI was maintained irrespective of GPI administration. GPI use was associated with substantially higher bleeding rates, regardless of the randomization to cangrelor or clopidogrel. (A Clinical Trial to Demonstrate the Efficacy of Cangrelor [PCI]: NCT00305162; Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition [PLATFORM]: NCT00385138; A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]: NCT01156571)",
keywords = "antiplatelet therapy, bleeding, coronary artery disease, outcomes",
author = "{on behalf of the} and {CHAMPION Investigators} and {CHAMPION Investigators} and Muthiah Vaduganathan and Harrington, {Robert A.} and Stone, {Gregg W.} and Deliargyris, {Efthymios N.} and Steg, {Ph Gabriel} and Gibson, {C. Michael} and Hamm, {Christian W.} and Price, {Matthew J.} and Alberto Menozzi and Jayne Prats and Steven Elkin and Mahaffey, {Kenneth W.} and White, {Harvey D.} and Bhatt, {Deepak L.} and Fernando Cura and Miguel Ballarino and Damonte, {Anibal Agust{\'i}n} and Diego Grinfeld and {\'A}lvarez, {Carlos Alejandro} and Alberto Fernandez and Ahmad Farshid and Brendan Gunalingam and Craig Jeurgens and Harry Lowe and Hisham Hallani and Greg Nelson and Gishel New and Ronald Dick and Jeffrey Lefkovits and Stephen Duffy and Nick Bett and Raibhan Yadav and Paul Garrahy and Ron Lehman and Philip Aylward and John Horowitz and Matthew Worthley and David Cross and Jaime Rankin and Peter Thompson and Phil Roberts-Thomson and David Cross and Rohan Jayasinghe and Con Aroney and Kurt Huber and Franz Leisch and Johann Altenberger and Georg Gaul and Thomas Neunteufl and Greenberg, {Mark A.}",
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TY - JOUR

T1 - Cangrelor With and Without Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Percutaneous Coronary Intervention

AU - on behalf of the

AU - CHAMPION Investigators

AU - CHAMPION Investigators

AU - Vaduganathan, Muthiah

AU - Harrington, Robert A.

AU - Stone, Gregg W.

AU - Deliargyris, Efthymios N.

AU - Steg, Ph Gabriel

AU - Gibson, C. Michael

AU - Hamm, Christian W.

AU - Price, Matthew J.

AU - Menozzi, Alberto

AU - Prats, Jayne

AU - Elkin, Steven

AU - Mahaffey, Kenneth W.

AU - White, Harvey D.

AU - Bhatt, Deepak L.

AU - Cura, Fernando

AU - Ballarino, Miguel

AU - Damonte, Anibal Agustín

AU - Grinfeld, Diego

AU - Álvarez, Carlos Alejandro

AU - Fernandez, Alberto

AU - Farshid, Ahmad

AU - Gunalingam, Brendan

AU - Jeurgens, Craig

AU - Lowe, Harry

AU - Hallani, Hisham

AU - Nelson, Greg

AU - New, Gishel

AU - Dick, Ronald

AU - Lefkovits, Jeffrey

AU - Duffy, Stephen

AU - Bett, Nick

AU - Yadav, Raibhan

AU - Garrahy, Paul

AU - Lehman, Ron

AU - Aylward, Philip

AU - Horowitz, John

AU - Worthley, Matthew

AU - Cross, David

AU - Rankin, Jaime

AU - Thompson, Peter

AU - Roberts-Thomson, Phil

AU - Cross, David

AU - Jayasinghe, Rohan

AU - Aroney, Con

AU - Huber, Kurt

AU - Leisch, Franz

AU - Altenberger, Johann

AU - Gaul, Georg

AU - Neunteufl, Thomas

AU - Greenberg, Mark A.

PY - 2017/1/17

Y1 - 2017/1/17

N2 - Background Cangrelor, an intravenous, reversible P2Y12 antagonist, is approved for use in patients undergoing percutaneous coronary intervention (PCI). Objectives This study sought to evaluate the efficacy and safety of cangrelor compared with clopidogrel in subgroups that did and did not receive glycoprotein IIb/IIIa inhibitors (GPIs). Methods This pooled, patient-level analysis of the 3 CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials analyzed all randomized patients who underwent PCI and received the study drug (n = 24,902). Only bailout/rescue GPI use was permitted, except in CHAMPION PCI, in which routine or bailout/rescue GPI use was at the site investigator's discretion. The primary efficacy endpoint was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h after randomization. Results Overall, 3,173 patients (12.7%) received a GPI, most commonly eptifibatide (69.4%). Despite variation in indications for GPIs, baseline characteristics were well balanced between the cangrelor and clopidogrel arms in subsets receiving and not receiving GPIs. Rates of the primary composite endpoint were lower with cangrelor compared with clopidogrel in patients who did (4.9% vs. 6.5%; odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.55 to 1.01) or did not receive a GPI (3.6% vs. 4.4%; OR: 0.82; 95% CI: 0.72 to 0.94; Pint = 0.55). Cangrelor did not increase the primary safety endpoint, GUSTO-defined severe/life-threatening bleeding, in patients who did (0.4% vs. 0.5%; OR: 0.71; 95% CI: 0.25 to 1.99) or did not receive GPIs (0.2% vs. 0.1%; OR: 1.56; 95% CI: 0.80 to 3.04; Pint = 0.21). GPI use was associated with increased risk of bleeding in both treatment arms. Conclusions Cangrelor's efficacy in reducing ischemic complications in patients undergoing PCI was maintained irrespective of GPI administration. GPI use was associated with substantially higher bleeding rates, regardless of the randomization to cangrelor or clopidogrel. (A Clinical Trial to Demonstrate the Efficacy of Cangrelor [PCI]: NCT00305162; Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition [PLATFORM]: NCT00385138; A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]: NCT01156571)

AB - Background Cangrelor, an intravenous, reversible P2Y12 antagonist, is approved for use in patients undergoing percutaneous coronary intervention (PCI). Objectives This study sought to evaluate the efficacy and safety of cangrelor compared with clopidogrel in subgroups that did and did not receive glycoprotein IIb/IIIa inhibitors (GPIs). Methods This pooled, patient-level analysis of the 3 CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials analyzed all randomized patients who underwent PCI and received the study drug (n = 24,902). Only bailout/rescue GPI use was permitted, except in CHAMPION PCI, in which routine or bailout/rescue GPI use was at the site investigator's discretion. The primary efficacy endpoint was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h after randomization. Results Overall, 3,173 patients (12.7%) received a GPI, most commonly eptifibatide (69.4%). Despite variation in indications for GPIs, baseline characteristics were well balanced between the cangrelor and clopidogrel arms in subsets receiving and not receiving GPIs. Rates of the primary composite endpoint were lower with cangrelor compared with clopidogrel in patients who did (4.9% vs. 6.5%; odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.55 to 1.01) or did not receive a GPI (3.6% vs. 4.4%; OR: 0.82; 95% CI: 0.72 to 0.94; Pint = 0.55). Cangrelor did not increase the primary safety endpoint, GUSTO-defined severe/life-threatening bleeding, in patients who did (0.4% vs. 0.5%; OR: 0.71; 95% CI: 0.25 to 1.99) or did not receive GPIs (0.2% vs. 0.1%; OR: 1.56; 95% CI: 0.80 to 3.04; Pint = 0.21). GPI use was associated with increased risk of bleeding in both treatment arms. Conclusions Cangrelor's efficacy in reducing ischemic complications in patients undergoing PCI was maintained irrespective of GPI administration. GPI use was associated with substantially higher bleeding rates, regardless of the randomization to cangrelor or clopidogrel. (A Clinical Trial to Demonstrate the Efficacy of Cangrelor [PCI]: NCT00305162; Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition [PLATFORM]: NCT00385138; A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]: NCT01156571)

KW - antiplatelet therapy

KW - bleeding

KW - coronary artery disease

KW - outcomes

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U2 - 10.1016/j.jacc.2016.10.055

DO - 10.1016/j.jacc.2016.10.055

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C2 - 28081827

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VL - 69

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EP - 185

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

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