title: Implications of different criteria for percutaneous coronary intervention-related myocardial infarction on study results of three large phase III clinical trials: The CHAMPION experience.
abstract: OBJECTIVE
  The purpose of this study was to test whether different results between Cangrelor versus standard therapy to acHieve optimal Management of Platelet InhibitiON (CHAMPION) PCI/PLATFORM and PHOENIX trials are due in part to different definitions of percutaneous coronary intervention (PCI)-related myocardial infarction (MI).
  
  
  RESULTS
  In patients with acute coronary syndrome (ACS), the definition of MI was identical in CHAMPION PCI and PLATFORM and did not require an assessment of baseline cardiac biomarker status, while in PHOENIX specific MI criteria were associated with different patient presentations. The same MI criteria were used in PCI, PLATFORM, and PHOENIX for patients with stable angina. Logistic regression assessed the effect of cangrelor on MI (PCI- and non-PCI related) in the combined PCI/PLATFORM population and in PHOENIX. Consistency of cangrelor's effect in PCI/PLATFORM and in PHOENIX in patients with stable angina and in those with an ACS (with or without ST elevation) was evaluated. Overall, the incidence of PCI-related MI at 48 h was 6.3% in PCI/PLATFORM and 4.0% in PHOENIX. In patients with ACS, MI incidence was 6.4% in PCI/PLATFORM and 1.7% in PHOENIX, and 6.3% and 5.6%, respectively in stable angina patients. Cangrelor's effect on PCI-related MI differed between PCI/PLATFORM (odds ratio (OR) 1.03, 95% confidence interval (CI) 0.90-1.17) and PHOENIX (OR 0.80, 95% CI 0.66-0.98) with pINT=0.04. This difference was mostly evident in patients with ACS ( pINT= 0.06) while the effect was consistent in patients with stable angina ( pINT=0.81). Results were similar when all MIs were analyzed.
  
  
  CONCLUSIONS
  The definition of PCI-related MI has important implications for event rates, treatment effect, and study results. This illustrates the importance of a rigorous assessment of PCI-related MI in clinical trials of patients with an ACS.
authors.affiliation: 1 Fondazione IRCCS Policlinico San Matteo, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Leonardi
authors.affiliation: 2 Duke Clinical Research Institute, USA.
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.affiliation: 3 FACT, DHU FIRE, INSERM U-1148, Paris, France.|4 Université Paris-Diderot, France.|5 Hôpital Bichat, Assistance-Publique-Hôpitaux de Paris, France.
authors.forename: Ph Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: 6 Department of Medicine, Stanford University, USA.
authors.forename: Freddy
authors.initials: F
authors.lastname: Abnousi
authors.affiliation: 7 Unità Operativa di Cardiologia, Azienda Ospedaliero-Universitaria di Parma, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Menozzi
authors.affiliation: 8 The Medicines Company, USA.
authors.forename: Jayne
authors.initials: J
authors.lastname: Prats
authors.affiliation: 2 Duke Clinical Research Institute, USA.
authors.forename: Stacey
authors.initials: S
authors.lastname: Mangum
authors.affiliation: 2 Duke Clinical Research Institute, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Wilson
authors.affiliation: 8 The Medicines Company, USA.
authors.forename: Meredith
authors.initials: M
authors.lastname: Todd
authors.affiliation: 9 Columbia University Medical Center, USA.|10 Cardiovascular Research Foundation, USA.
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
authors.affiliation: 11 Division of Cardiology, Beth Israel Deaconess Medical Center, USA.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Gibson
authors.affiliation: 12 Kerckhoff Heart and Thorax Center, Germany.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Hamm
authors.affiliation: 13 Scripps Clinic, USA.|14 Scripps Translational Science Institute, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Price
authors.affiliation: 15 Auckland City Hospital, Green Lane Cardiovascular Service, New Zealand.
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.affiliation: 6 Department of Medicine, Stanford University, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.affiliation: 16 Brigham and Women's Hospital Heart and Vascular Center, USA.|17 Harvard Medical School, USA.
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.affiliation: 6 Department of Medicine, Stanford University, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
mesh_terms: D054058:Acute Coronary Syndrome / Q000601:surgery*; D000249:Adenosine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology / Q000628:therapy*; D009520:New Zealand / Q000453:epidemiology; D016017:Odds Ratio; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D013988:Ticlopidine / Q000008:administration & dosage*; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D010975:Platelet Aggregation Inhibitors; D000249:Adenosine Monophosphate; C117446:cangrelor; D013988:Ticlopidine
keywords: Percutaneous coronary intervention; acute coronary syndrome; myocardial infarction; randomized controlled trial