What is the recommended use and dosage of Cangrelor (generic name) for patients undergoing percutaneous coronary intervention (PCI) who are at high risk for thrombotic events and have not received a P2Y12 inhibitor prior to the procedure?

Cangrelor for Percutaneous Coronary Intervention

Cangrelor should be administered as a 30 mcg/kg IV bolus immediately prior to PCI, followed by a 4 mcg/kg/min continuous infusion for at least 2 hours or the duration of the procedure, whichever is longer, specifically in P2Y12 inhibitor-naïve patients to reduce periprocedural myocardial infarction, stent thrombosis, and repeat revascularization. 1

Indications and Patient Selection

Cangrelor may be considered (Class IIb recommendation) in P2Y12 inhibitor-naïve patients undergoing PCI for both acute coronary syndromes and stable coronary disease. 2

The strongest evidence supports cangrelor use in the following clinical scenarios:

• Patients who have not received any oral P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) prior to PCI 1
• Patients unable to take or absorb oral medications (e.g., nausea, vomiting, intubation, cardiogenic shock) 2, 3
• Patients requiring urgent/emergent PCI where rapid, predictable platelet inhibition is critical 2, 3
• Patients who may require early CABG or other surgery after PCI, where the rapid offset of cangrelor (platelet function restored within 60 minutes) provides a safety advantage 2, 3

Dosing Protocol

The FDA-approved dosing regimen is straightforward 1:

• Bolus: 30 mcg/kg IV push over <1 minute, administered immediately before PCI
• Infusion: 4 mcg/kg/min continuous IV infusion
• Duration: Minimum 2 hours OR duration of procedure, whichever is longer
• Administration: Via dedicated IV line after reconstitution (5 mL sterile water per 50 mg vial) and dilution (add to 250 mL normal saline or D5W to achieve 200 mcg/mL concentration)

Patients weighing ≥100 kg require at least 2 bags prepared. 1

Transition to Oral P2Y12 Inhibitor

Transitioning to an oral P2Y12 inhibitor is mandatory after cangrelor discontinuation to maintain platelet inhibition. 1 The timing differs by agent:

• Ticagrelor 180 mg: Can be given at ANY time during the cangrelor infusion or immediately after discontinuation (no pharmacodynamic interaction) 1, 4
• Prasugrel 60 mg: Must be given immediately AFTER cangrelor discontinuation (cangrelor interferes with prasugrel's antiplatelet effect if given during infusion) 1
• Clopidogrel 600 mg: Must be given immediately AFTER cangrelor discontinuation (cangrelor interferes with clopidogrel's antiplatelet effect if given during infusion) 1

Evidence Base and Efficacy

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 (odds ratio favoring cangrelor), with consistent benefits across both NSTE-ACS and STEMI populations. 2

A pooled patient-level meta-analysis of all three CHAMPION trials (24,910 patients) showed cangrelor reduced stent thrombosis by 41% compared to clopidogrel. 3, 5

The benefit was particularly pronounced for:

• Periprocedural and intraprocedural stent thrombosis prevention 2
• Reduction in periprocedural myocardial infarction 2, 3

Safety Profile and Bleeding Risk

Major bleeding rates are similar between cangrelor and clopidogrel, but minor bleeding (primarily access site hematomas) occurs more frequently with cangrelor. 2, 3, 1

Key safety considerations:

• Cangrelor is contraindicated in patients with significant active bleeding 1
• Once discontinued, antiplatelet effect resolves within 60 minutes, providing a safety advantage if urgent surgery is needed 2, 1
• Do NOT use cangrelor concurrently with GP IIb/IIIa inhibitors (this was an exclusion criterion in approval trials) 1

Common Pitfalls to Avoid

1. Do NOT administer clopidogrel or prasugrel during the cangrelor infusion - this blocks their antiplatelet effect and leaves the patient unprotected after cangrelor discontinuation 1

2. Do NOT use cangrelor in patients already loaded with an oral P2Y12 inhibitor - the indication is specifically for P2Y12-naïve patients 1

3. Do NOT forget to transition to oral therapy - cangrelor's effect disappears within 60 minutes of stopping the infusion 1

4. Do NOT use the same IV line for other medications - cangrelor requires a dedicated line 1

5. Do NOT use cangrelor with GP IIb/IIIa inhibitors - this combination was not studied and is not approved 1

Guideline Recommendations Summary

• ACC/AHA 2025: Class IIb (may be reasonable) for P2Y12-naïve patients undergoing PCI 2
• ESC 2018/2019: Class IIb (may be considered) for P2Y12-naïve patients undergoing PCI in both ACS and stable CAD 2

The moderate strength of recommendation (Class IIb) reflects that while cangrelor reduces ischemic events, oral agents (particularly ticagrelor and prasugrel) remain first-line when they can be administered and absorbed effectively. 2