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*

doi:10.1161/CIRCULATIONAHA.115.020829

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)

Circulation. 2016 Sep 6;134(10):723-33. doi: 10.1161/CIRCULATIONAHA.115.020829. Epub 2016 Aug 1.

Affiliations

¹ From University of North Carolina, Chapel Hill (M.A.C.); Brigham and Women's Hospital, Heart and Vascular Center, Harvard Medical School, Boston, MA (D.L.B.); Columbia University, New York, NY (G.W.S.); University of Auckland, Auckland City Hospital, Auckland, New Zealand (H.D.W.); Université Paris-Diderot, Sorbonne Paris Cité, INSERM U-1148, DHU FIRE, Hópital Bichat, Assistance Publique-Hópitaux de Paris, Paris, France (P.G.S.); Institute of Cardiovascular Medicine and Science, National Lung and Heart Institute, Imperial College, Royal Brompton Hospital, London, United Kingdom (P.G.S.); Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.M.G.); Kerckhoff Clinic and Thoraxcenter, Bad Nauheim, Germany (C.W.H.); Scripps Clinic, La Jolla, CA (M.J.P.); UOC Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (S.L.); The Medicines Company, Parsippany, NJ (J.P., E.N.D.); and Stanford University, Palo Alto, CA (K.W.M., R.A.H.).
² From University of North Carolina, Chapel Hill (M.A.C.); Brigham and Women's Hospital, Heart and Vascular Center, Harvard Medical School, Boston, MA (D.L.B.); Columbia University, New York, NY (G.W.S.); University of Auckland, Auckland City Hospital, Auckland, New Zealand (H.D.W.); Université Paris-Diderot, Sorbonne Paris Cité, INSERM U-1148, DHU FIRE, Hópital Bichat, Assistance Publique-Hópitaux de Paris, Paris, France (P.G.S.); Institute of Cardiovascular Medicine and Science, National Lung and Heart Institute, Imperial College, Royal Brompton Hospital, London, United Kingdom (P.G.S.); Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.M.G.); Kerckhoff Clinic and Thoraxcenter, Bad Nauheim, Germany (C.W.H.); Scripps Clinic, La Jolla, CA (M.J.P.); UOC Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (S.L.); The Medicines Company, Parsippany, NJ (J.P., E.N.D.); and Stanford University, Palo Alto, CA (K.W.M., R.A.H.). dlbhattmd@post.harvard.edu.

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: http://clinicaltrials.gov. Unique identifier: NCT01156571.

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

Publication types

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

MeSH terms

Adenosine Monophosphate / administration & dosage
Adenosine Monophosphate / analogs & derivatives*
Aged
Clopidogrel
Disease Management
Double-Blind Method
Female
Humans
Infusions, Intravenous
Male
Middle Aged
Myocardial Infarction / diagnosis
Myocardial Infarction / drug therapy*
Myocardial Infarction / etiology
Percutaneous Coronary Intervention / adverse effects*
Percutaneous Coronary Intervention / methods
Perioperative Care / methods*
Platelet Aggregation Inhibitors / administration & dosage
Purinergic P2Y Receptor Antagonists / administration & dosage*
Ticlopidine / administration & dosage
Ticlopidine / analogs & derivatives*

Substances

Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Adenosine Monophosphate
cangrelor
Clopidogrel
Ticlopidine

Associated data

ClinicalTrials.gov/NCT01156571