Cangrelor and Glycoprotein IIb/IIIa Inhibitors

Study Questions:

What is the efficacy and safety of cangrelor compared with clopidogrel in patients who did and did not receive platelet glycoprotein IIb/IIIa inhibitors (GPIs)?

Methods:

The authors reported the pooled, patient-level analysis of the three CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials, which compared cangrelor with clopidogrel in patients undergoing percutaneous coronary intervention (PCI). Only bailout/rescue GPI use was permitted, except in the CHAMPION PCI trial, in which routine or bailout/rescue GPI use was at the site investigator’s discretion. The primary efficacy endpoint was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours after randomization.

Results:

GPIs were used in 3,173 patients (12.7%), with eptifibatide being the most commonly used agent (69.4%), whereas abciximab was used in 19.4% and tirofiban in 10.8%. Of the GPI-treated patients, bailout/rescue use was in 745 patients (23.5%), whereas the remaining 2,428 (76.5%) received GPIs routinely as a part of site standard of care. Rates of the primary composite endpoint were lower with cangrelor compared with clopidogrel in patients who did (4.9% vs. 6.5%; odds ratio [OR], 0.74; 95% confidence interval [CI], 0.55-1.01) or did not receive a GPI (3.6% vs. 4.4%; OR, 0.82; 95% CI, 0.72-0.94; pint = 0.55). Cangrelor did not increase the primary safety endpoint, GUSTO-defined severe/life-threatening bleeding, in patients who did (0.4% vs. 0.5%; OR, 0.71; 95% CI, 0.25-1.99) or did not receive GPIs (0.2% vs. 0.1%; OR, 1.56; 95% CI, 0.80-3.04; pint = 0.21). GPI use was associated with an increased risk of bleeding in both treatment arms.

Conclusions:

The authors concluded that cangrelor demonstrated similar efficacy and safety compared with clopidogrel in the presence or absence of GPI use.

Perspective:

The clinical role for cangrelor in contemporary practice is yet to be defined given the multiple agents and therapeutic combinations that are used across the country. This study suggests that among the patients who received GPIs, the benefits of cangrelor were preserved, but it remains unclear if cangrelor can be used as a substitute for GPIs. The use of GPIs has declined and clopidogrel has been supplanted in the cath lab with more potent P2Y12 inhibitors (prasugrel and ticagrelor). Since it is unlikely that there will be future randomized trials to compare GPIs with cangrelor, well-done comparative effectiveness studies are needed to define the ideal patient for this novel agent.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Aortic Surgery

Keywords: Blood Platelets, Ischemia, Myocardial Infarction, Myocardial Revascularization, Percutaneous Coronary Intervention, Platelet Glycoprotein GPIIb-IIIa Complex, Standard of Care, Stents, Thrombosis


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