In a patient with acute coronary syndrome receiving intravenous cangrelor, when and how should oral P2Y12 inhibitors be started?

Transitioning from IV Cangrelor to Oral P2Y12 Inhibitors in ACS

Administer ticagrelor 180 mg at any time during or immediately after the cangrelor infusion, prasugrel 60 mg immediately after stopping cangrelor (or up to 30 minutes before), and clopidogrel 600 mg only after discontinuing cangrelor—never give clopidogrel or prasugrel during the infusion due to competitive receptor blockade. 1

Timing Algorithm by P2Y12 Inhibitor

Ticagrelor (Preferred Transition)

• Give 180 mg at any time during the cangrelor infusion or immediately after discontinuation 1
• No drug interaction exists because both are reversible P2Y12 antagonists that do not compete for binding 2, 3
• Maintains seamless platelet inhibition without any gap in coverage 3
• Pharmacodynamic studies confirm ticagrelor's antiplatelet effects are fully preserved when administered during cangrelor infusion 3

Prasugrel

• Give 60 mg immediately after discontinuing cangrelor 1
• Alternative: Can administer up to 30 minutes before stopping cangrelor 2
• Critical pitfall: Do NOT give prasugrel during active cangrelor infusion—cangrelor blocks the binding of prasugrel's active metabolite to the P2Y12 receptor 2, 4
• The active metabolite of prasugrel has a short half-life in blood, requiring precise timing 2
• Recent trial data shows prasugrel 60 mg given at the start of a 2-hour cangrelor infusion achieved 93.3% adequate platelet inhibition 1 hour post-cangrelor, though this contradicts FDA labeling 5

Clopidogrel (Least Preferred)

• Give 600 mg only after completely stopping cangrelor 1
• Never administer during cangrelor infusion—competitive receptor blockade eliminates clopidogrel's sustained platelet inhibition 4
• Pharmacodynamic studies demonstrate that simultaneous administration results in loss of expected clopidogrel effect 4
• Creates a transient gap in platelet inhibition compared to ticagrelor or prasugrel strategies 5
• Only 65% of patients achieve adequate platelet inhibition 1 hour post-cangrelor with this approach 5

Cangrelor Infusion Protocol

• Bolus: 30 mcg/kg IV push over <1 minute prior to PCI 1
• Infusion: 4 mcg/kg/min for at least 2 hours or duration of PCI, whichever is longer 1
• Platelet function returns to baseline within 1 hour of stopping cangrelor 6
• Provides immediate, profound platelet inhibition superior to oral agents during the periprocedural period 7

Clinical Context for Use

The 2025 ACC/AHA guidelines give cangrelor a Class IIb recommendation (may be reasonable) in P2Y12 inhibitor-naïve patients undergoing PCI to reduce periprocedural ischemic events 6. Cangrelor is particularly valuable when:

• Oral medication absorption is impaired (shock, nausea, vomiting) 6
• Patient cannot take oral medications 6
• Early CABG or surgery anticipated when prolonged P2Y12 inhibitor discontinuation would be unsafe 6
• High thrombus burden requiring immediate, reliable platelet inhibition 7

Evidence Base

The CHAMPION PHOENIX trial demonstrated cangrelor reduced death, MI, ischemia-driven revascularization, or stent thrombosis at 48 hours compared to clopidogrel (7.5% vs 8.9%, p=0.005), with a 41% reduction in stent thrombosis 6. This benefit was consistent in both NSTE-ACS and STEMI populations 6. Major bleeding rates were similar between cangrelor and clopidogrel, though minor bleeding was more frequent with cangrelor 6.

Critical Pitfalls to Avoid

• Do not give thienopyridines (clopidogrel, prasugrel) during active cangrelor infusion—the competitive receptor blockade will negate their effect and leave patients unprotected after cangrelor stops 1, 2, 4
• Do not delay oral loading beyond cangrelor discontinuation—this creates a dangerous gap in platelet inhibition 5
• Ticagrelor is the only oral P2Y12 inhibitor that can be safely given during cangrelor infusion without loss of efficacy 1, 2, 3