Cangrelor: a review on pharmacology and clinical trial development

Abstract

Dual antiplatelet therapy with aspirin and an oral ADP P2Y₁₂ receptor antagonist is the standard-of-care for the prevention of ischemic events in patients with acute coronary syndrome or undergoing percutaneous coronary intervention (PCI). However, currently available ADP P2Y₁₂ receptor antagonists have several limitations, such as interindividual response variability, drug–drug interactions, slow onset/offset and only oral availability. Cangrelor is a reversible, potent, intravenous, competitive inhibitor of the ADP P2Y₁₂ receptor that rapidly achieves near complete and predictable platelet inhibition. Along with reversible binding to the receptor cangrelor also has a very short half-life (3–5 min), which in turn results in a rapid offset of action. These properties make cangrelor a promising drug for clinical use in patients undergoing PCI or patients waiting for major surgery but still require antiplatelet protection. This manuscript provides an update of the current status of knowledge on cangrelor, focusing on its pharmacologic properties and clinical trial development, including the BRIDGE and CHAMPION-PHOENIX trials.

Keywords::

• acute coronary syndrome
• antiplatelet therapy
• cangrelor
• percutaneous coronary intervention
• P2Y₁₂ receptor antagonist

Financial & competing interests disclosure

DJ Angiolillo received payment as a consulting fee or honorarium from Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, Merck, Evolva, Abbott Vascular and PLx Pharma, and for participation in review activities from Johnson & Johnson, St. Jude and Sunovion. DJ Angiolillo has received institutional payments for grants from Bristol-Myers Squibb, Sanofi-Aventis, GlaxoSmithKline, Otsuka, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZenecaand Evolva. DJ Angiolillo has other financial relationships with Esther and King Biomedical Research Grant. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Dual antiplatelet therapy with aspirin and oral ADP P2Y₁₂ receptor antagonists is currently the standard of care for prevention of ischemic events in patients with acute coronary syndrome and undergoing percutaneous coronary intervention.

• • Despite the proven clinical benefit associated with currently available P2Y₁₂ receptor inhibiting therapy, clopidogrel, prasugrel and ticagrelor present several drawbacks, such slow onset of action, in particular in patients with ST-elevation myocardial infarction, slow offset and only oral availability.

• • Cangrelor is a direct, potent, reversible, competitive inhibitor of the P2Y₁₂ receptor that rapidly achieves near complete inhibition of ADP-induced platelet aggregation administered by intravenous infusion.

• • The BRIDGE trial showed cangrelor to be a feasible treatment option as a smooth and effective bridging strategy in patients on thienopyridine therapy who require coronary artery bypass graft.

• • The results of the Phase III CHAMPION PHOENIX trial demonstrated the efficacy of cangrelor in addition to standard-of-care therapy in the reduction of the peri-percutaneous coronary intervention ischemic complications in a wide spectrum of clinical settings.

• • Studies investigating the use of cangrelor in addition to prasugrel and ticagrelor as well as the transition between these new antiplatelet agents are warranted.