Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data

Lancet. 2013 Dec 14;382(9909):1981-92. doi: 10.1016/S0140-6736(13)61615-3. Epub 2013 Sep 3.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / therapy
  • Adenosine Monophosphate / analogs & derivatives*
  • Adenosine Monophosphate / therapeutic use
  • Aged
  • Cause of Death
  • Coronary Disease / therapy
  • Double-Blind Method
  • Female
  • Graft Occlusion, Vascular / etiology
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / therapy
  • Myocardial Ischemia / therapy*
  • Myocardial Revascularization / statistics & numerical data
  • Percutaneous Coronary Intervention / methods*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Stents
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Adenosine Monophosphate
  • cangrelor