CHAMPION: Cangrelor Bests Clopidogrel in PCI Patients in Large Meta-analysis

AMSTERDAM, The Netherlands— Among patients undergoing percutaneous coronary intervention (PCI), the intravenous ADP-receptor antagonist cangrelor reduces periprocedural events compared with clopidogrel, according to results presented on September 2, 2013, at the European Society of Cardiology Congress and simultaneously published in the Lancet. However, the data, derived from the CHAMPION trials, show increased mild bleeding with the newer drug.

For the CHAMPION meta-analysis, Christian W. Hamm, MD, of the Kerckhoff Heart Center (Bad Nauheim, Germany), and colleagues pooled patients from 3 prior trials comparing cangrelor (The Medicines Company, Parsippany, NJ; n = 12,475) and clopidogrel (n = 12,435) for the prevention of thrombotic complications during and after PCI for STEMI (11.6%), NSTE-ACS (57.4%), and stable CAD (31.0%):

• CHAMPION-PHOENIX (n = 10,942)
• CHAMPION-PCI (n = 8,667)
• CHAMPION-PLATFORM (n = 5,301)

CHAMPION-PHOENIX, published this April in the New England Journal of Medicine, showed that cangrelor substantially reduces ischemic events across the entire spectrum of PCI patients.

Efficacy Increased With Minimal Bleeding Consequence

Cangrelor reduced the combined risk of death, MI, ischemia-driven revascularization, or stent thrombosis (primary efficacy outcome) at 48 hours by 19% compared with clopidogrel. Individually, death only trended lower with cangrelor (table 1).

Table 1. Efficacy Outcomes at 48 Hours

 
The findings were maintained at 30 days as well as within prespecified subgroups including those with biomarker elevations at baseline, diabetes, and ≥ 75 years.

Data for all-cause death at 1 year were collected from the CHAMPION-PCI and CHAMPION-PLATFORM studies only; rates did not differ between the cangrelor (3.3%) and control groups (3.7%; OR 0.89; 95% CI 0.75-1.07; P = 0.2200).

Overall, angiographic procedural complications were reduced by cangrelor (OR 0.81; 95% CI 0.71-0.92; P = 0.0014), with a marked reduction in new or suspected thrombus, acute stent thrombosis, and the need for bailout GPI treatment.

There was no difference in GUSTO severe bleeding (primary safety outcome), which was 0.2% in both groups, or in blood transfusion rates, but cangrelor increased GUSTO mild bleeding compared with clopidogrel (16.8% vs. 13.0%; P < 0.0001).

“Intravenous cangrelor may be an attractive option across the full spectrum of PCI; stable angina, NSTEMI, and STEMI,” Dr. Hamm concluded, although he acknowledged that the comparator arms differed among the 3 original trials in terms of timing, loading dose, and whether or not patients were clopidogrel naive.

Comparison with Newer Agents Needed

According to discussant Stefan James, MD, PhD, of the Uppsala Clinical Research Center (Uppsala, Sweden), cangrelor “is fast acting, consistent, reliable, and it has a fast offset reaction, so maybe it’s an attractive option for treating PCI patients, particularly in those with acute coronary syndromes.”

The meta-analysis “confirms the results of the CHAMPION-PHOENIX trial,” he said. “The strategy of cangrelor over clopidogrel reduces thrombotic complications periprocedurally and early postprocedurally.” Importantly, the meta-analysis “also suggests that there are some clinically meaningful advantages to this strategy sustained out to 30 days,” Dr. James added.

Nonetheless, while the study “fills some gaps in the knowledge, it opens space for new questions,” he said. Specifically, Dr. James focused on determining what the results may have been had a more potent agent such as prasugrel or ticagrelor replaced clopidogrel in the comparator arm.

In an editorial accompanying the paper, Shamir R Mehta, MD, MSc, of McMaster University (Hamilton, Canada), agreed that the newer drugs deserve attention. “Although cangrelor might be complementary to a simultaneous loading dose of ticagrelor or prasugrel, there is a possibility that it will offer little additional benefit and safety will require careful evaluation,” he writes.

Dr. Mehta also zoned in on cangrelor’s cost-effectiveness since the difference between the intravenous infusion of cangrelor and a loading dose of an oral antiplatelet drug, such as ticagrelor, prasugrel, or clopidogrel, is “likely to be substantial. Moreover, the degree to which the reduction in ischemic events makes cangrelor an overall cost-effective strategy will be a major determinant of how widely it is used.”

Despite these caveats, the “favorable pharmacodynamic profile and effectiveness in reducing periprocedural events makes cangrelor a useful and welcome agent for interventional cardiologists and their patients,” he concluded.

Study Details

Overall, the mean age was 63.0 years, and 72.3% were men. About one-third of patients (29.6%) had diabetes mellitus, and 53.2% received DES.

 

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Sources:
1. Steg PG, Bhatt DL, Hamm CW, et al. Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: A pooled analysis of patient-level data. Lancet; 2013:Epub ahead of print.

2. Mehta SR. Cangrelor: A new CHAMPION for percutaneous coronary intervention. Lancet; 2013:Epub ahead of print.

 

 

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