Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of
Philippe Gabriel Steg1, Deepak L Bhatt2, Christian W Hamm3
1Université Paris-Diderot, Sorbonne Paris-Cité, Paris, France; Département Hospitalo-Universitaire FIRE, Hôpital Bichat, AP-HP, INSERM U-698, Paris, France.
Insights
Cangrelor significantly reduced thrombotic complications during percutaneous coronary intervention (PCI), including stent thrombosis. However, this benefit came with an increased risk of mild bleeding events.
Area of Science:
- Cardiology
- Pharmacology
- Interventional Cardiology
Background:
- Cangrelor is an intravenous platelet inhibitor used in percutaneous coronary intervention (PCI).
- Three large randomized trials assessed cangrelor's efficacy against clopidogrel or placebo in PCI.
- A pooled analysis of these trials provides comprehensive data on cangrelor's effectiveness and safety.
Purpose of the Study:
- To evaluate the effectiveness of cangrelor in preventing thrombotic complications during and after PCI.
- To compare cangrelor with control treatments (clopidogrel or placebo) in a large patient population undergoing PCI.
- To assess the safety profile of cangrelor, specifically focusing on bleeding events.
Main Methods:
- Pooled analysis of patient-level data from three trials (CHAMPION-PCI, CHAMPION-PLATFORM, CHAMPION-PHOENIX).
- Included 24,910 patients undergoing PCI for various coronary conditions (STEMI, NSTE-ACS, stable CAD).
- Primary efficacy endpoint: composite of death, myocardial infarction, revascularization, or stent thrombosis at 48 hours. Primary safety endpoint: severe or life-threatening bleeding at 48 hours.
Main Results:
- Cangrelor reduced the primary composite outcome by 19% (3.8% vs 4.7%) and stent thrombosis by 41% (0.5% vs 0.8%).
- Secondary composite outcomes also showed significant reduction with cangrelor, with benefits maintained at 30 days.
- No significant difference in severe bleeding, but cangrelor use was associated with a significant increase in mild bleeding (16.8% vs 13.0%).
Conclusions:
- Cangrelor effectively reduces periprocedural thrombotic complications in patients undergoing PCI.
- The benefits of cangrelor in reducing thrombotic events are significant and consistent across patient subgroups.
- Increased mild bleeding is a notable safety consideration when using cangrelor compared to clopidogrel or placebo.
Background:
Cangrelor is a potent, rapid-acting, reversible intravenous platelet inhibitor that was tested for percutaneous coronary intervention (PCI) in three large, double-blind, randomised trials. We did a pooled analysis of data from three trials that assessed the effectiveness of cangrelor against either clopidogrel or placebo in PCI.
Methods:
This prespecified, pooled analysis of patient-level data from three trials (CHAMPION-PCI, CHAMPION-PLATFORM, and CHAMPION-PHOENIX) compared cangrelor with control (clopidogrel or placebo) for prevention of thrombotic complications during and after PCI. Trial participants were patients undergoing PCI for ST-elevation myocardial infarction (11.6%), non-ST-elevation acute coronary syndromes (57.4%), and stable coronary artery disease (31.0%). Efficacy was assessed in the modified intention-to-treat population of 24,910 patients, with a prespecified primary efficacy composite of death, myocardial infarction, ischaemia-driven revascularisation, or stent thrombosis at 48 h. The primary safety outcome was non-coronary artery bypass graft-related GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe or life-threatening bleeding at 48 h.
Findings:
Cangrelor reduced the odds of the primary outcome by 19% (3.8% for cangrelor vs 4.7% for control; odds ratio [OR] 0.81, 95% CI 0.71-0.91, p=0.0007), and stent thrombosis by 41% (0.5% vs 0.8%, OR 0.59, 95% CI 0.43-0.80, p=0.0008). Cangrelor reduced the odds of the secondary triple composite (all-cause death, myocardial infarction, or ischaemia-driven revascularisation at 48 h) by 19% (3.6% vs 4.4%, OR 0.81, 95% CI 0.71-0.92, p=0.0014). Efficacy outcomes were consistent across the trials and main patient subsets. These benefits were maintained at 30 days. There was no difference in the primary safety outcome (0.2% in both groups), in GUSTO moderate bleeding (0.6% vs 0.4%), or in transfusion (0.7% vs 0.6%), but cangrelor increased GUSTO mild bleeding (16.8% vs 13.0%, p<0.0001).
Interpretation:
Compared with control (clopidogrel or placebo), cangrelor reduced PCI periprocedural thrombotic complications, at the expense of increased bleeding.
Funding:
The Medicines Company.
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