Cardiac Matters

Cangrelor (Kengreal) is the first and currently only, FDA-approved injectable P2Y₁₂‑ inhibitor available for use in the United States. Cangrelor exerts its effect on platelets by directly and reversibly blocking ADP-mediated activation, aggregation, and subsequent downstream signaling. This drug is indicated for patients undergoing percutaneous coronary intervention (PCI) who have not been treated with an alternative P2Y₁₂ inhibitor or a glycoprotein IIb/IIIa inhibitor, such as eptifibatide or tirofiban.¹

The pivotal CHAMPION PHOENIX trial found that IV cangrelor significantly reduced the composite of all-cause mortality, myocardial infarction, revascularization due to ischemia, and stent thrombosis as compared to oral clopidogrel therapy when given at the time of PC12.

Conventional dosing of cangrelor is 30 mcg/kg administered as a bolus injection followed by a continuous infusion of 4 mcg/kg/min for 2 hours or for the duration of the procedure-whichever is longer. A loading dose of an oral P2Y₁₂ inhibitor should be given  upon discontinuation of the infusion. If ticagrelor is chosen, however, the oral dose may be given at any point during the infusion.¹

Off-label uses of cangrelor have begun to make their way into hospitals around the country following the drug’s approval. One such off-label indication that has modest clinical trial data to support its use is “bridge” therapy prior to non-emergent coronary artery bypass graft (CABG) surgery. In the cangrelor BRIDGE study (not to be confused with the recently published Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation study), patients taking oral antiplatelet agents were transitioned to either a prespecified low-dose continuous infusion of cangrelor (0.75 mcg/kg/min) or placebo.³ The primary goal of the BRIDGE trial was to determine if adequate platelet inhibition was maintained while the infusion was administered before surgery. Additionally, patients were assessed for the main safety endpoint of surgery-related bleeding.

A larger percentage of patients treated with cangrelor maintained suppressed platelet activity during the infusion as compared to placebo (98.8% vs. 19.0%; p < 0.001). Rates of surgery-related bleeding did not differ significantly between patients treated with cangrelor  or placebo (11.8% vs. 10.4%; p = 0.76) and all other adverse event rates were similar between the two groups.³

There is a concern that ischemic events may occur following the discontinuation of oral antiplatelet therapies before non-emergent cardiothoracic surgery. Conversely, if antiplatelet agents are not discontinued with enough time for platelets to recover prior to surgery, then patients could be at an increased risk of bleeding during surgery. Cangrelor offers a theoretical advantage as a bridging therapy compared to traditionally used oral thienopyridines due its short pharmacokinetic (t1/2 = 3 to 6 minutes) and pharmacodynamic half-life (platelet recovery ~ 1 hour).1 The BRIDGE study provides a rationale for use of cangrelor in this clinical setting, though the use of a surrogate efficacy marker as a primary outcome limits the widespread generalizability of the results to practice.

References
1. The Medicines Company. Kengreal® Package Insert. Parsippany, NJ; 2016, May.
2. Bhatt DL, Stone GW, Mahaffey KW, et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368(14):1303-13.
3. Angiolillo DJ, Firstenberg MS, Price MJ, et al. Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA. 2012 Jan 18;307(3):265-74.