Consistent Reduction in Periprocedural Myocardial Infarction With Cangrelor as Assessed by Multiple Definitions: Findings From CHAMPION PHOENIX (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition)

Matthew A Cavender, Deepak L Bhatt, Gregg W Stone, Harvey D White, Ph Gabriel Steg, C Michael Gibson, Christian W Hamm, Matthew J Price, Sergio Leonardi, Jayne Prats, Efthymios N Deliargyris, Kenneth W Mahaffey, Robert A Harrington, CHAMPION PHOENIX Investigators*, Matthew A Cavender, Deepak L Bhatt, Gregg W Stone, Harvey D White, Ph Gabriel Steg, C Michael Gibson, Christian W Hamm, Matthew J Price, Sergio Leonardi, Jayne Prats, Efthymios N Deliargyris, Kenneth W Mahaffey, Robert A Harrington, CHAMPION PHOENIX Investigators*

Abstract

Background: Cangrelor is an intravenous P2Y12 inhibitor approved to reduce periprocedural ischemic events in patients undergoing percutaneous coronary intervention not pretreated with a P2Y12 inhibitor.

Methods: A total of 11 145 patients were randomized to cangrelor or clopidogrel in the CHAMPION PHOENIX trial (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition). We explored the effects of cangrelor on myocardial infarction (MI) using different definitions and performed sensitivity analyses on the primary end point of the trial.

Results: A total of 462 patients (4.2%) undergoing percutaneous coronary intervention had an MI as defined by the second universal definition. The majority of these MIs (n=433, 93.7%) were type 4a. Treatment with cangrelor reduced the incidence of MI at 48 hours (3.8% versus 4.7%; odds ratio [OR], 0.80; 95% confidence interval [CI], 0.67-0.97; P=0.02). When the Society of Coronary Angiography and Intervention definition of periprocedural MI was applied to potential ischemic events, there were fewer total MIs (n=134); however, the effects of cangrelor on MI remained significant (OR, 0.65; 95% CI, 0.46-0.92; P=0.01). Similar effects were seen in the evaluation of the effects of cangrelor on MIs with peak creatinine kinase-MB ≥10 times the upper limit of normal (OR, 0.64; 95% CI, 0.45-0.91) and those with peak creatinine kinase-MB ≥10 times the upper limit of normal, ischemic symptoms, or ECG changes (OR, 0.63; 95% CI, 0.48-0.84). MIs defined by any of these definitions were associated with increased risk of death at 30 days. Treatment with cangrelor reduced the composite end point of death, MI (Society of Coronary Angiography and Intervention definition), ischemia-driven revascularization, or Academic Research Consortium definite stent thrombosis (1.4% versus 2.1%; OR, 0.69; 95% CI, 0.51-0.92).

Conclusions: MI in patients undergoing percutaneous coronary intervention, regardless of definition, remains associated with increased risk of death in the current era. Cangrelor compared with clopidogrel significantly reduces MI regardless of the definition.

Clinical trial registration: URL: https://ichgcp.net/clinical-trials-registry/NCT01156571" title="See in ClinicalTrials.gov">NCT01156571.

Keywords: creatine kinase, MB form; myocardial infarction; percutaneous coronary intervention.

© 2016 The Authors.

Figures

Figure 1.
Figure 1.
Protocol-defined and sensitivity analyses of primary efficacy end points at 48 hours using different definitions of myocardial infarction (MI).ARC indicates Academic Research Consortium; CI, confidence interval; CK-MB, creatinine kinase-MB; IDR, ischemia-driven revascularization; OR, odds ratio; SCAI, Society of Coronary Angiography and Intervention; ST, stent thrombosis; and ULN, upper limit of normal.
Figure 2.
Figure 2.
Sensitivity analyses evaluating outcomes at 48 hours of cangrelor compared with clopidogrel using different definitions of myocardial infarction (MI).Time to first occurrence of (A) death, MI (Society of Coronary Angiography and Intervention [SCAI] definition), ischemia-driven revascularization (IDR), and Academic Research Consortium (ARC) definite stent thrombosis (ST) and (B) death, MI (creatinine kinase-MG [CK-MB] ≥10 times the upper limit of normal [ULN]), IDR, and ARC definite stent thrombosis. OR indicates odds ratio.
Figure 3.
Figure 3.
Association between the types of myocardial infarction (MI) using various definitions and the risk of death at 30 days.CHF indicates coronary heart failure; CI, confidence interval; CK-MB, creatinine kinase-MB; MI, myocardial infarction; OR, odds ratio; PCI, percutaneous coronary intervention; SCAI, Society of Coronary Angiography and Intervention; and ULN, upper limit of normal.

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