AT EUROPCR 2016
PARIS (FRONTLINE MEDICAL NEWS) – Parenteral cangrelor is a potent antiplatelet agent that provides similar anti-ischemic effects but a significantly lower risk of major bleeding than the popular combination of clopidogrel plus a glycoprotein IIb/IIIa inhibitor in patients undergoing elective or urgent percutaneous coronary intervention.
Moreover, cangrelor (Kengreal), a rapid-acting and reversible intravenous platelet P2Y12 inhibitor, cuts the blood transfusion requirement by more than half, Dr. Muthiah Vaduganathan reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
These findings, based upon a propensity score–matched exploratory pooled analysis of individual patient-level data from the three phase III CHAMPION trials, suggest that cangrelor alone is an attractive alternative to clopidogrel plus a glycoprotein IIb/IIIa inhibitor (GPI) for antiplatelet management in percutaneous coronary intervention (PCI), according to Dr. Vaduganathan of Brigham and Women’s Hospital, Boston.
CHAMPION PLATFORM ( N Engl J Med 2009 Dec 10;361[24]:2330-41 ), CHAMPION PCI ( N Engl J Med 2009 Dec 10;361[24]:2318-29 ), and CHAMPION PHOENIX ( N Engl J Med 2013 Apr 11;368[14]:1303-13 ) collectively included nearly 25,000 patients randomized to cangrelor versus standard therapy for platelet inhibition in elective or urgent PCI. The trials, which established that cangrelor led to fewer ischemic complications within 30 days post PCI than did clopidogrel plus a GPI, led to Food and Drug Administration approval of the drug in 2015. Cangrelor is also approved in Europe.
The cangrelor and clopidogrel groups differed in terms of baseline bleeding risk. For example, the clopidogrel-treated patients were younger, more likely to be male, had fewer comorbid conditions, and more often presented with an acute coronary syndrome. In order to accurately assess the bleeding risk associated with the two antiplatelet strategies, Dr. Vaduganathan and coinvestigators engaged in propensity score matching on the basis of 16 baseline clinical variables. They identified two closely matched cohorts consisting of 1,021 patient pairs.
The 1,021 patients in the cangrelor-alone group had a 2.6% rate of the primary composite efficacy endpoint consisting of all-cause mortality, MI, ischemia-driven revascularization, or stent thrombosis at 48 hours. Although this was 21% lower than the 3.3% rate in the clopidogrel plus GPI group, the difference didn’t achieve statistical significance because of the relatively small sample size.
In contrast, the rate of major bleeding within 48 hours by ACUITY (Acute Catheterization and Urgent Intervention Triage) criteria did differ significantly between the two groups: 3.6% with cangrelor and 5.8% with clopidogrel plus a GPI, for a 39% relative risk reduction in favor of the newer agent. Major bleeding rates were also lower in the cangrelor-treated patients on the GUSTO (Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries) and TIMI (Thrombolysis in Myocardial Infarction) scales, although those trends didn’t achieve significance. The blood transfusion requirement was significantly lower in the cangrelor group: 1% versus 2.1%, for a 55% relative risk reduction.
Dr. Vaduganathan said the CHAMPION investigators’ future plans include examining the possibility of a favorable pharmacologic interaction between cangrelor and bivalirudin, a combination seeing increasing use in the United States.
“Finally, I think it’ll be important moving forward to look at comparative effectiveness data – either observational or randomized – as well as cost-effectiveness data between potent parenteral antiplatelet strategies,” he concluded.
Session chair Dr. Anthony Gershlick of Glenfield General Hospital in Leicester, England, commented that while he found this analysis of the CHAMPION data quite interesting, they are of little relevance in Europe, where cardiologists seldom use GPIs as part of their up-front PCI management strategy, instead resorting to those agents mainly as bailout therapy.
The U.S. situation is very different, according to Dr. Vaduganathan. American cardiologists use GPI therapy in about one-third of PCIs.
The CHAMPION trials were funded by the Medicines Co. Dr. Vaduganathan reported having no relevant financial conflicts.
