CHAMPION PHOENIX Analysis: Cangrelor Reduces Early Stent Thrombosis, Suggesting Mortality Benefit

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Use of the novel intravenous ADP-receptor antagonist cangrelor reduces the risk of intraprocedural as well as acute and subacute stent thrombosis in patients undergoing percutaneous coronary intervention (PCI), according to an angiographic analysis of the CHAMPION PHOENIX trial. With stent thrombosis strongly associated with increased mortality, the potent fast-acting antiplatelet agent appears to decrease risk both in the cath lab and within the first 30 days postprocedure.    

The findings were presented by Philippe Généreux, MD, of Columbia University Medical Center (New York, NY), at the American College of Cardiology/i2 Scientific Session in Washington, DC, March 30, 2014.  

Selected data from the analysis were first presented at the Transcatheter Cardiovascular Therapeutics scientific session in San Francisco, CA, in October 2013. 

In the main trial, published in the New England Journal of Medicine in April 2013, 10,942 patients undergoing PCI were randomized to receive either a bolus and infusion of cangrelor (The Medicines Company, Parsipanny, NJ; n = 5,472) or a loading dose of 600 mg or 300 mg of clopidogrel (n = 5,470). Use of cangrelor reduced periprocedural and 30-day ischemic events, including stent thrombosis, without increasing severe bleeding.   

For the substudy, data from 10,939 trial participants were analyzed by an independent core laboratory. Intraprocedural stent thrombosis occurred in 89 patients (0.8%), while Academic Research Consortium (ARC)-defined acute events were seen in 32 patients (0.3%) within 24 hours, and subacute stent thrombosis occurred in 60 patients (0.5%) between 24 hours and 30 days postprocedure.  

Each type of stent thrombosis was associated with substantially increased 30-day mortality: 

• Intraprocedural (OR 17.4; 95% CI 8.4-36.1) 
• Acute (OR 43.3; 95% CI 18.1-103.5) 
• Subacute (OR 189.1; 95% CI 107.9-331.4; all P < 0.001)   

Cangrelor Effective Against All Early Stent Thrombosis  

Cangrelor was associated with a reduction in both 48-hour and 30-day stent thrombosis (0.8% vs 1.4% and 1.3% vs 1.9%, respectively; both P = 0.01). Moreover, the novel antiplatelet drug consistently reduced the risk of 3 types of early stent thrombosis, with no interaction between event timing and efficacy (P for interaction = 0.48; table 1). 

Table 1. Stent Thrombosis Risk with Cangrelor vs Clopidogrel by Time from Procedure

On multivariable analysis, cardiac biomarkers at baseline, longer stent length, PAD, and smoking predicted increased risk of stent thrombosis at 30 days, while male gender and use of cangrelor predicted reduced risk: 

• Positive cardiac biomarkers at baseline: adjusted OR 2.05; P < 0.0001 
• Total stent length (per 1-mm increase): adjusted OR 1.02; P < 0.0001 
• PAD: adjusted OR 1.94; P = 0.013 
• Male gender: adjusted OR 0.68; P = 0.03 
• Smoking status: adjusted OR 1.43; P = 0.048 
• Cangrelor at randomization (vs clopidogrel): adjusted OR 0.66; P = 0.02  

In addition, use of a DES vs a BMS specifically reduced 30-day ARC-defined stent thrombosis (OR 0.57; 95% CI 0.35-0.92; P = 0.02). 

Reducing Early Stent Thrombosis May Have Mortality Impact   

“Regardless of the exact type of stent thrombosis, it remains associated with a high rate of death,” observed Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital (Boston, MA), co-chair of the CHAMPION program, in a press statement.  

In an email with TCTMD, study coauthor Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), zeroed in on intraprocedural events. “The message from this dataset is that half of all stent thromboses at 30 days occur intraprocedurally,” he said. “Ignoring this subset of events is not reasonable because they are associated with increased mortality. Thus, any intervention that reduces intraprocedural stent thrombosis may reduce overall mortality.    

“We have shown in other analyses that intraprocedural stent thrombosis also predicts ARC stent thrombosis, which is another reason we should try to prevent intraprocedural events,” Dr. Brener added. 

Study Details  

Stent thrombosis was defined as occurrence of either intraprocedural stent thrombosis (any new or worsened thrombus related to the stent procedure that was confirmed angiographically) or ARC-defined definite or probable stent thrombosis.   

Note: Drs. Généreux and Brener as well as coauthor Gregg W. Stone, MD, are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

Source:
Généreux P. Incidence and impact of stent thrombosis during percutaneous coronary intervention: comparison of cangrelor and clopidogrel from the CHAMPION PHOENIX trial. Presented at: American College of Cardiology/i2 Scientific Session; March 30, 2014. 

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