Cangrelor Use and Dosing in Percutaneous Coronary Intervention
Cangrelor may be reasonable in P2Y12 inhibitor-naïve patients undergoing PCI to reduce periprocedural ischemic events, administered as a 30 mcg/kg IV bolus followed by a 4 mcg/kg/min infusion for at least 2 hours or the duration of the procedure, whichever is longer. In patients undergoing PCI who are P2Y12 inhibitor naïve, intravenous cangrelor may be reasonable to reduce periprocedural ischemic events.
Pharmacological Properties and Clinical Benefits
- Cangrelor is a potent, direct, reversible, short-acting intravenous P2Y12 inhibitor with rapid onset of platelet inhibition and restoration of platelet function within 1 hour of discontinuation 1
- It provides rapid, predictable, and profound inhibition of platelets, making it particularly beneficial in scenarios where oral P2Y12 inhibitors have impaired absorption or cannot be administered 1, 2
- Cangrelor is characterized by linear, dose-dependent pharmacokinetics with a half-life of 2.9 to 5.5 minutes, allowing for precise control of antiplatelet effect 2
- In the CHAMPION PHOENIX trial, cangrelor significantly reduced the primary endpoint of death, MI, ischemia-driven revascularization, or stent thrombosis at 48 hours compared to clopidogrel 1
- A pooled patient-level meta-analysis of CHAMPION trials demonstrated a 41% reduction in stent thrombosis with cangrelor compared to clopidogrel 1
Recommended Dosing Regimen
- Administer a 30 mcg/kg IV bolus prior to PCI 3
- Follow immediately with a 4 mcg/kg/min IV infusion 3
- Continue infusion for at least 2 hours or for the duration of PCI, whichever is longer 3
- Administer via a dedicated IV line after reconstitution and dilution 3
- For preparation: reconstitute each 50 mg vial with 5 mL of Sterile Water for Injection, then dilute in 250 mL normal saline or 5% dextrose 3
Transitioning to Oral P2Y12 Therapy
- To maintain platelet inhibition after discontinuation of cangrelor infusion, administer an oral P2Y12 inhibitor as follows 3:
- Ticagrelor: 180 mg at any time during cangrelor infusion or immediately after discontinuation
- Prasugrel: 60 mg immediately after discontinuation of cangrelor
- Clopidogrel: 600 mg immediately after discontinuation of cangrelor
Clinical Scenarios for Optimal Use
- Most beneficial in P2Y12 inhibitor-naïve patients undergoing PCI 1
- Particularly valuable in patients where absorption of oral medications may be inhibited or in those unable to take oral medications 1, 2
- Potentially beneficial in patients with ST-segment elevation myocardial infarction, those treated with opioids, with mild therapeutic hypothermia, or in cardiogenic shock 2
- May be considered in patients requiring CABG or other surgery early after PCI when prolonged discontinuation of a P2Y12 inhibitor may not be safe 1, 4
Safety Considerations
- Bleeding events of all severities were more common with cangrelor than with clopidogrel in clinical trials 3
- Major bleeding was similar between cangrelor and clopidogrel groups, but minor bleeding was more frequent in the cangrelor group 1
- The ARCANGELO study confirmed the safety of cangrelor in real-world practice, with only 0.5% of patients experiencing moderate bleeding events 5
- Contraindicated in patients with significant active bleeding or known hypersensitivity to cangrelor 3
Limitations and Caveats
- There are no studies comparing cangrelor with a loading dose of ticagrelor or prasugrel given at the time of PCI 1
- The clinical role of cangrelor in conjunction with administration of prasugrel or ticagrelor remains unclear 6
- Cangrelor has a Class IIb recommendation (may be reasonable) in current guidelines, indicating moderate strength of evidence 1
- Cost considerations may limit widespread use in all PCI procedures, suggesting targeted use in specific high-risk scenarios 4