How should cangrelor (intravenous reversible P2Y12 inhibitor) be dosed and used in adult patients undergoing percutaneous coronary intervention?

Cangrelor Dosing and Use in Percutaneous Coronary Intervention

Administer cangrelor as a 30 mcg/kg IV bolus immediately before PCI, followed by a 4 mcg/kg/min continuous infusion for at least 2 hours or for the duration of the procedure, whichever is longer. 1

Indications and Patient Selection

Cangrelor may be reasonable in P2Y12 inhibitor-naïve patients undergoing PCI to reduce periprocedural ischemic events including myocardial infarction, repeat revascularization, and stent thrombosis. 2, 3 This represents a Class IIb recommendation from the 2025 ACC/AHA guidelines. 3

Specific Clinical Scenarios Where Cangrelor Offers Particular Benefit:

• Patients unable to take or absorb oral P2Y12 inhibitors (e.g., nausea, vomiting, intubation, cardiogenic shock, or impaired gastrointestinal absorption). 2, 3

• Patients requiring CABG or other surgery early after PCI when prolonged discontinuation of oral P2Y12 inhibitors may be unsafe, as cangrelor's effects resolve within 60 minutes of stopping the infusion. 2

• ST-elevation myocardial infarction patients where delayed bioavailability of oral agents is most problematic. 4

Evidence Base

The CHAMPION PHOENIX trial demonstrated that cangrelor significantly reduced the composite endpoint of death, MI, ischemia-driven revascularization, or stent thrombosis at 48 hours compared to clopidogrel (7.0% vs 8.0%), with consistent benefits in both NSTE-ACS (n=2,810) and STEMI (n=1,991) patients. 2 Pooled meta-analysis showed a 41% reduction in stent thrombosis with cangrelor versus clopidogrel. 3, 5

Important context: Earlier trials (CHAMPION PLATFORM and CHAMPION PCI) showed neutral results, likely due to differences in clopidogrel timing and endpoint definitions. 2

Administration Details

Preparation and Delivery:

• Use a dedicated IV line only after reconstitution and dilution. 1

• Administer the bolus prior to PCI, then immediately start the infusion. 2, 1

• Continue infusion for minimum 2 hours or procedure duration, whichever is longer. 2, 1

Contraindications:

• Significant active bleeding. 1

• Hypersensitivity to cangrelor or any component. 1

Critical Transition Strategy to Oral P2Y12 Inhibitors

The transition from cangrelor to oral P2Y12 inhibitors requires precise timing to avoid gaps in platelet inhibition, as cangrelor competitively blocks the binding of clopidogrel and prasugrel active metabolites to P2Y12 receptors. 2, 6

Transition Protocols:

For Ticagrelor:

• Administer ticagrelor 180 mg loading dose at any time during cangrelor infusion or immediately upon discontinuation. 2
• Ticagrelor binds to a different site than cangrelor and is not affected by competitive inhibition. 2

For Prasugrel:

• Administer prasugrel 60 mg loading dose immediately after discontinuation of cangrelor infusion—do NOT give during infusion. 1
• In vitro studies show cangrelor strongly inhibits prasugrel active metabolite binding (only 34.1% receptor blockade when co-administered). 6

For Clopidogrel:

• Administer clopidogrel 600 mg loading dose immediately after discontinuation of cangrelor infusion—do NOT give during infusion. 1
• Cangrelor reduces clopidogrel active metabolite binding to only 11.7% when co-administered. 6

Common Pitfall to Avoid:

Real-world data from the CAMEO registry revealed that 16.4% of patients had >1 hour gap between cangrelor cessation and oral P2Y12 inhibitor initiation, with the highest gap (56.6%) occurring with clopidogrel transitions. 7 This gap creates a window of inadequate platelet inhibition and increased thrombotic risk. Ensure immediate administration of oral agents upon stopping cangrelor (except ticagrelor, which can be given during infusion). 7

Safety Profile

• Major bleeding rates are similar between cangrelor and clopidogrel (3.6% vs 2.9%). 2

• Minor bleeding is more frequent with cangrelor (17.6% vs 15.2%, p=0.003). 2

• Real-world data from the ARCANGELO study (n=995) showed bleeding occurred in 5.2% of patients within 30 days, with only 0.5% experiencing moderate (BARC 3) bleeding. 8

Pharmacological Properties

Cangrelor provides >90% platelet inhibition within 30 minutes of starting infusion, with a half-life of 3-5 minutes and restoration of platelet function within 60 minutes of discontinuation. 2, 4 This rapid offset makes it uniquely suited for patients requiring urgent surgery post-PCI. 2