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

AIMS:

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).

METHODS AND 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: Sergio Leonardi, Renato D Lopes, Ph Gabriel Steg, Freddy Abnousi, Alberto Menozzi, Jayne Prats, Stacey Mangum, Matthew Wilson, Meredith Todd, Gregg W Stone, C Michael Gibson, Christian W Hamm, Matthew J Price, Harvey D White, Robert A Harrington, Deepak L Bhatt, Kenneth W Mahaffey
• Journal: European heart journal. Acute cardiovascular care (Eur Heart J Acute Cardiovasc Care) Vol. 7 Issue 2 Pg. 158-165 (Mar 2018) ISSN: 2048-8734 [Electronic] England
• PMID: 27485140 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Platelet Aggregation Inhibitors
• Adenosine Monophosphate
• cangrelor
• Ticlopidine

Topics

• Acute Coronary Syndrome (surgery)
• Adenosine Monophosphate (administration & dosage, analogs & derivatives)
• Aged
• Dose-Response Relationship, Drug
• Double-Blind Method
• Europe (epidemiology)
• Female
• Humans
• Incidence
• Male
• Middle Aged
• Myocardial Infarction (epidemiology, etiology, therapy)
• New Zealand (epidemiology)
• Odds Ratio
• Percutaneous Coronary Intervention (adverse effects)
• Platelet Aggregation Inhibitors (administration & dosage)
• Ticlopidine (administration & dosage)
• Treatment Outcome
• United States (epidemiology)