In an exploratory analysis of the CHAMPION (Cangrelor vs Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials, cangrelor was found to have a similar ischemic risk and reduced bleeding risk compared with clopidogrel glycoprotein IIb/IIIa inhibitors (GPIs).
The researchers, led by Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital Heart & Vascular Center in Boston, sought to compare these risks between the 2 treatments in patients undergoing percutaneous coronary intervention (PCI). Their results were published in JAMA: Cardiology.
The CHAMPION program includes CHAMPION PCI, CHAMPION PLATFORM, and CHAMPION PHOENIX (ClinicalTrials.gov identifiers: NCT00305162, NCT00385138, and NCT01156571, respectively). Each was a prospective, double-blind, double-dummy, randomized clinical trial. More specifically, rescue GPI therapy was only allowed in CHAMPION PHOENIX and PLATFORM in the event of PCI-related thrombotic complications, whereas planned procedural GPI therapy was permitted in CHAMPION PCI at the discretion of the PCI operator.
A total of 12,140 patients were included in this pooled analysis (72.3% men; mean age: 63.2 years). The primary efficacy end point was a composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours, assessed in the modified intention-to-treat population (ie, patients who underwent index PCI and received the study drug).
To assess safety end points, GUSTO (Global Use of Strategies to Open Occluded Arteries), TIMI (Thrombolysis in Myocardial Infarction), and ACUITY (Acute Catheterization and Urgent Intervention Triage) bleeding scales were used. Bleeding risks were assessed in patients who underwent randomization and received the study drug.
The cangrelor alone and clopidogrel-GPI groups did not have significantly different rates of the primary efficacy end point (2.6% vs 3.3%; odds ratio [OR]: 0.79; 95% confidence interval [CI], 0.48-1.32).
In addition, the patients in the cangrelor alone group had a “nonsignificant trend toward” lower GUSTO-defined severe/life-threatening bleeding compared with the clopidogrel-GPI group (0.3% vs 0.7%; OR: 0.43; 95% CI, 0.11-1.66). However, TIMI-defined major or minor bleeding rates were significantly lower in the cangrelor alone group (0.7% vs 2.4%; OR: 0.29; 95% CI, 0.13-0.68). Finally, in the ACUITY-defined major bleeding assessment, patients in the cangrelor alone group experienced lower rates of bleeding compared with the clopidogrel-GPI group (3.6% vs 5.8%; OR: 0.61; 95% CI, 0.40-0.94).
Blood transfusions were less often required in the cangrelor group as well (1.0% vs 2.1%; OR: 0.45; 95% CI, 0.20-0.99).
“Most patients included in the present analysis presented with an ACS [acute coronary syndrome] and, as such, our data primarily reflect this experience and inform, to a lesser extent, stable coronary artery disease,” the authors noted. “Emerging data have suggested that bivalirudin may complement the antiplatelet efficacy of cangrelor while limiting attendant bleeding hazards in contemporary PCI.”
They concluded, however, that further research is necessary to validate that strategy.
- Matched comparisons were used in the absence of randomized data which may have biased and confounded the analysis due to “unmeasured or unknown covariates.”
- Incomplete propensity-score matching data.
- The CHAMPION trials were not originally designed or powered to compare cangrelor with GPIs.
Vaduganathan M, Harrington RA, Stone GW, et al. Evaluation of ischemic and bleeding risks associated with parenteral antiplatelet strategies comparing cangrelor with glycoprotein IIb/IIIa inhibitors. An exploratory analysis from the CHAMPION trials. JAMA Cardiol. 2016 Nov 30. doi:10.1001/jamacardio.2016.4556 [Epub ahead of print].