Response by Cavender et al to Letter Regarding Article, “Ischemic Events Occur Early in Patients Undergoing Percutaneous Coronary Intervention and Are Reduced With Cangrelor: Findings From CHAMPION PHOENIX”

Abstract

We agree that the evidence supports the importance of early and potent platelet P2Y 12 inhibition with cangrelor during percutaneous coronary intervention. 1 The authors cited a meta-analysis of the three trials in the cangrelor CHAMPION (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) program that only analyzed subgroups with type 2 diabetes. However, the pooled, patient-level meta-analysis of these three trials 2 is more informative because the investigators were able to harmonize outcome definitions. In this analysis, the odds ratio for death, myocardial infarction (MI), ischemia-driven revascularization, or stent thrombosis was 0.87 (95% CI, 0.69-1.09) in type 2 diabetes patients and 0.63 (95% CI, 0.41-0.98) in patients with insulin-dependent diabetes, and along with nonsignificant interaction P, this does suggest an overall consistency in outcomes with the current study.The cangrelor trial referenced by Zaghloul et al 3 was CHAMPION PLATFORM, 1 of the 3 trials mentioned above. After CHAMPION PLATFORM and CHAMPION PCI were stopped early by an independent committee that felt the trials were unlikely to reach their primary end point, careful analysis of the data suggested that the MI definition in these trials was not sufficient to discriminate between an ischemic event in progress and a postpercutaneous coronary intervention event. Therefore, the MI definitions used were not able to adequately discern an actual treatment effect of cangrelor on MI. Nevertheless, as Zaghloul et al note, stent thrombosis and death were both significantly lower with cangrelor in CHAM-PION PLATFORM. The pivotal trial that led to Food and Drug Administration approval of cangrelor for percutaneous coronary intervention, CHAMPION PHOENIX

Periprocedural myocardial infarction in patients undergoing complex versus noncomplex percutaneous coronary intervention

“…In fact, a subgroup analysis of the CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention) trial showed that the majority of ischemic events (63%) occurred within 2 h after PCI and during this timeframe cangrelor decreased by 34% this risk compared with clopidogrel. Conversely, between 2 and 48 h after PCI, ischemic events occurred at similar rates between the cangrelor and clopidogrel 40 …”

Letter by Zaghloul et al Regarding Article, “Ischemic Events Occur Early in Patients Undergoing Percutaneous Coronary Intervention and Are Reduced With Cangrelor: Findings From CHAMPION PHOENIX”

“…We read with interest the recent article by Cavender et al, 1 which demonstrated the results of the CHAMPION PHOENIX trial (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention), which was a double-blind, placebo-controlled trial that randomized patients undergoing percutaneous coronary intervention (PCI) to cangrelor or clopidogrel. In the first 2 hours, after randomization, cangrelor significantly decreased the primary composite end point compared with clopidogrel (4.1% versus 5.4%).…”