Cangrelor – short acting P2Y12 inhibitor for intravenous use

Cangrelor

Cangrelor is a short acting P2Y12 inhibitor for intravenous use. It is a directly acting non thienopyridine P2Y12 receptor antagonist analogous to adenosine triphosphate molecule, having a molecular weight of 88 Daltons. Plasma half life of the drug is 3 to 6 minutes only and the offset of its therapeutic action occurs in about one hour. If we are planning to use the drug in the cath lab, loading dose of oral P2Y12 inhibitor in the emergency department can be withheld.

The drug can be considered as Class IIb, level of evidence A indication for those undergoing percutaneous coronary intervention when they have not been treated with P2Y12 inhibitors earlier [1]. This is because of early onset of antiplatelet action. In case urgent surgery is needed, early offset of action is an added advantage.

In fact, cangrelor has been considered as a bridge therapy while withholding oral P2Y12 inhibitors prior to elective surgery in those with high risk of coronary thrombosis as in those with a recently implanted drug eluting coronary stent. This bridging is considered in the 5-7 days during which an antiplatelet agent is withheld prior to surgery.

BRIDGE trial evaluated patients taken for coronary artery bypass grafting. In that study, cangrelor was discontinued 1-6 hours prior to surgery, while aspirin was continued throughout the perioperative period. Bridging with cangrelor did not increase major bleeds prior to surgery, though minor bleeds, mostly ecchymosis at venipuncture site, was higher. P2Y₁₂ assay documented sufficient platelet inhibition corresponding to levels required for anti thrombotic effect [2].

CHAMPION PHOENIX was a double blind placebo controlled trial which randomized 11,145 patients undergoing urgent or elective PCI and were receiving guideline recommended therapy. They would receive either a bolus and infusion of cangrelor or a loading dose of 600 mg or 300 mg clopidogrel. Cangrelor significantly reduced ischemic events including stent thrombosis during PCI with no significant increase in severe bleeding [3].

SWAP-5 Study was a randomized double blind placebo controlled crossover trial. It was a pharmacokinetic and pharmacodynamic study in 20 patients with coronary artery disease pre-treated with a 180 mg loading dose of ticagrelor and randomized to either placebo or cangrelor bolus and infusion for 2 hours. Crossover was after 1-4 weeks of wash out. Compared with placebo, use of cangrelor in patients pre-treated with ticagrelor resulted in enhanced platelet inhibition. There were no differences in pharmacokinetic and pharmacodynamic profiles after discontinuation of drug infusion, indicating the absence of a drug-drug interaction [4].

References

1. De Luca L, Steg PG, Bhatt DL, Capodanno D, Angiolillo DJ. Cangrelor: Clinical Data, Contemporary Use, and Future Perspectives. J Am Heart Assoc. 2021 Jul 6;10(13):e022125. doi: 10.1161/JAHA.121.022125. Epub 2021 Jul 2. PMID: 34212768; PMCID: PMC8403274.
2. Angiolillo DJ, Firstenberg MS, Price MJ, Tummala PE, Hutyra M, Welsby IJ, Voeltz MD, Chandna H, Ramaiah C, Brtko M, Cannon L, Dyke C, Liu T, Montalescot G, Manoukian SV, Prats J, Topol EJ; BRIDGE Investigators. Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA. 2012;307:265–274.
3. Bhatt DL, Stone GW, Mahaffey KW, Gibson CM, Steg PG, Hamm CW, Price MJ, Leonardi S, Gallup D, Bramucci E, Radke PW, Widimský P, Tousek F, Tauth J, Spriggs D, McLaurin BT, Angiolillo DJ, Généreux P, Liu T, Prats J, Todd M, Skerjanec S, White HD, Harrington RA; CHAMPION PHOENIX Investigators. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013 Apr 4;368(14):1303-13. doi: 10.1056/NEJMoa1300815. Epub 2013 Mar 10. PMID: 23473369.
4. Franchi F, Ortega-Paz L, Rollini F, Galli M, Been L, Ghanem G, Shalhoub A, Ossi T, Rivas A, Zhou X, Pineda AM, Suryadevara S, Soffer D, Zenni MM, Angiolillo DJ. Cangrelor in Patients with Coronary Artery Disease Pre-treated with Ticagrelor: The Switching Antiplatelet (SWAP)-5 Study. JACC Cardiovasc Interv. 2022 Oct 21:S1936-8798(22)02005-2. doi: 10.1016/j.jcin.2022.10.034. Epub ahead of print. PMID: 36317958.