Effect of platelet inhibition with cangrelor during PCI on ischemic events

Bhatt DL, Stone GW, Mahaffey KW, et al; for the CHAMPION PHOENIX Investigators. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368(14):1303-1313.

Background 

Percutaneous coronary intervention (PCI) with stent implantation is frequently used to reduce ischemic complications among patients with acute coronary syndrome (ACS). Despite advances in adjunctive pharmacologic therapy, thrombotic complications during PCI remain a concern.

Antiplatelet therapies (P2Y12 receptor inhibitors and glycoprotein [GP] IIb/IIIa inhibitors) reduce ischemic event risk, especially stent thrombosis. But the effect of these agents is often blunted as a result of complications during the acute phase of cardiovascular illness, as well as pharmacokinetic and pharmacodynamic variants. 

Cangrelor* is an intravenous, fast-acting, potent, direct-acting adenosine diphosphate (ADP) P2Y12 inhibitor with quickly reversible effects. The Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION) PHOENIX study assessed whether cangrelor reduces ischemic complications of PCI. (Click here for slide) 

 Design  

In CHAMPION PHOENIX, a total of 10,942 patients were randomly assigned cangrelor or clopidogrel pre-PCI; all patients had stable angina, non–ST-segment elevation acute coronary syndrome (NSTE-ACS), or ST-segment elevation myocardial infarction (STEMI). 

After randomization, patients were given a cangrelor infusion or matching placebo, and clopidogrel loading of 600 mg or 300 mg, or matching placebo. After the infusion, the cangrelor group received clopidogrel 600 mg, and the clopidogrel group received matching placebo. The study protocol also required:  (Click here for slide) 

  • All patients to receive aspirin therapy (75-325 mg)
  • Clopidogrel 75 mg during first 48 hours; thereafter, clopidogrel or another P2Y12 inhibitor
  • Periprocedural anticoagulant
  • GP IIb/IIIa inhibitors as rescue therapy only 

The primary efficacy endpoint was a composite of all-cause mortality, myocardial infarction (MI), ischemia-driven revascularization, or stent thrombosis 48 hours post-randomization. The primary safety endpoint was Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) severe bleeding at 48 hours not related to coronary artery bypass grafting (CABG). The key secondary efficacy endpoint was incidence of stent thrombosis at 48 hours (includes definite stent thrombosis [ST]). (Click here for slide) 

Select baseline characteristics for the study population are shown below. The median time from hospital admission to PCI was 4.4 hours. (Click here for slide) 

  Cangrelor (N=5,472)  Clopidogrel (N=5,470) 
Median age, yr 64.0 64.0
Diagnosis at presentation    
   Stable angina 3,121 (57%) 3,019 (55.2%)
   NSTE-ACS 1,389 (25.4%) 1,421 (26.0%)
   STEMI 962 (17.6%) 1,030 (18.8%)
Drug-eluting stent 3,061 (55.9%) 3,020 (55.2%)
Bare-metal stent      2,308 (42.2%) 2,344 (42.9%)

Results  

The rate of the primary efficacy endpoint was 4.7% in the cangrelor group and 5.9% in the clopidogrel group (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.66-0.93; P=0.005). The number needed to treat with cangrelor to prevent one primary endpoint event was 84 (95% CI, 49-285). (Click here for slide) 

The rate of the primary efficacy endpoint at 30 days was 6.0% in the cangrelor group and 7.0% in the clopidogrel group (OR, 0.85; 95% CI, 0.73-0.99; P=0.03). (Click here for slide) 

The rate of the key secondary efficacy endpoint was 0.8% in the cangrelor group and 1.4% in the clopidogrel group (OR, 0.62; 95% CI, 0.43-0.90; P=0.01). (Click here for slide) 

The rate of the primary safety endpoint was 0.16% in the cangrelor group and 0.11% in the clopidogrel group (OR, 1.50; 95% CI, 0.53-4.22; P=0.44). (Click here for slide)  

The rate of intraprocedural stent thrombosis was 0.6% in the cangrelor group and 1.0% in the clopidogrel group (OR, 0.65; 95% CI, 0.42-0.99; P=0.04). (Click here for slide)  

The rate of adverse events was similar between the cangrelor and clopidogrel groups: 20.2% vs 19.9% (P=0.13). In the cangrelor group, 0.5% of adverse events led to discontinuation of the study drug compared with 0.4% in the clopidogrel group (P=0.21). Transient dyspnea was significantly more frequent with cangrelor: 1.2% vs 0.3% with clopidogrel. (Click here for slide) 

*Cangrelor is an investigational agent that is not FDA approved for use in the United States.

 

March 2013 

This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.  

Last Modified: 8/5/2014