The Pre-brief
Fall is my favorite season, but this year I’ll be preparing for virtual Friendsgiving events since in-person tasting experiences are on hold due to COVID-19. On the bright side, this means there will be plenty of buttery, baked good recipe trials in my future…and no one to have to share with. (Surely, I cannot be the only one utilizing the scientific method to determine the superiority of cookie dough and pie crusts, right?)
Therefore, it seemed appropriate to provide an autumnal update on the use of cangrelor in case you find yourself in a cardiovascular bind this season.
What is cangrelor?
Cangrelor is an intravenous version of a direct P2Y12 inhibitor, similar to clopidogrel, prasugrel, and ticagrelor. Cangrelor binds reversibly to the P2Y12 receptor resulting in inhibition of platelet activation. In contrast, clopidogrel and prasugrel irreversibly bind the P2Y12 receptor, thus preventing further signaling and platelet activation for the lifespan of the platelet (7-10 days). Ticagrelor reversibly binds the P2Y12 receptor, but exerts platelet-inhibiting effects longer than cangrelor.1
What makes cangrelor a unique P2Y12 inhibitor?
When should cangrelor be considered?
- Patients unable to take periprocedural oral P2Y12 inhibitor, e.g. patient found down in cardiac arrest taken emergently for PCI.
- Cangrelor is FDA approved as adjunct to PCI to reduce the risk of periprocedural MI, repeat coronary revascularization, and stent thrombosis in patients not pre-treated with a P2Y12 platelet inhibitor and not being given a glycoprotein IIb/IIIa inhibitor.1
- The CHAMPION-PHOENIX study randomized 11,145 patients requiring PCI for stable angina, NSTEMI, or STEMI without previous treatment with platelet inhibitors to either cangrelor or placebo with procedural anticoagulation at the discretion of investigator. All patients received aspirin 75-325 mg and clopidogrel 75 mg within 48 hours of PCI. Significant reductions in the composite endpoint of death from any cause, MI, ischemia driven revascularization, or stent thrombosis were seen at 48 hours with cangrelor (4.7%) vs. clopidogrel (5.9%), OR 0.78 (95% CI 0.66-0.93, p=0.005) and at 30 days, 6% vs. 7%, OR 0.85 (95% CI 0.73-0.99, p=0.03). No significant differences in adverse events were seen between groups with the exception of a higher incidence of access site hematoma in the cangrelor group.2
- For bridge therapy in patients requiring P2Y12 inhibitors, but the long duration of antiplatelet effects seen with traditional oral agents is problematic in the setting of planned surgery. Additionally, it may be an attractive option for patients with a fresh stent who ultimately experience significant bleeding and are now awaiting intervention for definitive bleeding control.
- While cangrelor is not FDA approved for use as bridge therapy, its rapid reversibility may be useful in the above situations.
- The BRIDGE study randomized 210 patients with a coronary stent and receiving a P2Y12 inhibitor to either cangrelor or placebo while waiting for CABG planned within the next 2-7 days. Study drug was continued up until 1-6 hours prior to surgical incision. A significantly higher proportion of patients had platelet reactivity <240 PRU for all samples assessed during drug infusion prior to CABG in the cangrelor group (98.8%) vs. placebo (19.0%), p<0.001. There was no significant different in CABG related bleeding among groups, but there was more minor bleeding during study drug infusion (ecchymosis at venipuncture site). The major limitation of this study was inadequate power to detect a difference in ischemic events.3
How is cangrelor dosed?
- PCI: 30 mcg/kg bolus prior to PCI followed immediately by an infusion of 4 mcg/kg/minute continued for at least 2 hours or for the duration of the PCI, whichever is longer1
- Bridge: 0.75 mcg/kg/min as a continuous infusion3
Transitioning patients to oral antiplatelet after PCI:1
References:
- Kengreal® (cangrelor) [package insert]. Cary, NC: Chiesi USA, Inc; September 2020.
- Bhatt DL, Stone GW, Mahaffey KW, et al; CHAMPION PHOENIX Investigators. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013; 368(14):1303-13.
- Angiolillo DJ, Firstenberg MS, Price MJ, et al; BRIDGE Investigators. Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA. 2012; 307(3):265-74.
