What is the recommended IV (intravenous) P2Y12 (purinergic receptor P2Y12) inhibitor for acute coronary syndromes?

From the Guidelines

Cangrelor is the recommended intravenous P2Y12 inhibitor for acute coronary syndromes. It is administered as an initial bolus of 30 mcg/kg followed by a continuous infusion of 4 mcg/kg/min for at least 2 hours or for the duration of the procedure, whichever is longer. The maximum recommended duration of infusion is 4 hours. Cangrelor provides immediate and potent platelet inhibition, with a rapid onset of action within minutes and a short half-life of 3-6 minutes, allowing for quick reversal of its effects after discontinuation. This pharmacokinetic profile makes it particularly valuable in situations requiring urgent procedures, in patients unable to take oral medications, or when rapid platelet inhibition is needed. Cangrelor works by directly and reversibly binding to the P2Y12 receptor, preventing ADP-induced platelet aggregation. Unlike oral P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor), cangrelor doesn't require hepatic conversion to an active metabolite, enabling its immediate antiplatelet effect. When transitioning to oral therapy, ticagrelor can be given at any time during cangrelor infusion, while clopidogrel and prasugrel should be administered immediately after discontinuing cangrelor to prevent a gap in platelet inhibition, as supported by the 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for the management of patients with acute coronary syndromes 1.

Some key points to consider when using cangrelor include:

• Its rapid onset and short half-life make it ideal for situations where quick platelet inhibition is necessary
• It can be used in patients who are unable to take oral medications
• It is particularly useful in clinical scenarios where absorption of orally administered P2Y12 inhibitors is impaired or not possible
• The safety and efficacy of cangrelor have been compared with clopidogrel or placebo in 3 RCTs involving patients who are P2Y12 inhibitor-naïve and undergoing PCI for stable or acute indications, as noted in the 2025 guideline 1
• The transition from intravenous to oral P2Y12 inhibition is an important consideration to ensure adequate platelet inhibition on completion of cangrelor infusion, with recommendations for transitioning to oral therapy supported by the 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation 1.

Overall, cangrelor is a valuable option for the management of acute coronary syndromes, particularly in situations where rapid platelet inhibition is necessary, and its use is supported by recent guidelines, including the 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline 1 and the 2020 ESC guidelines 1.

From the Research

IV P2Y12 Inhibitors for Acute Coronary Syndromes

• The recommended IV P2Y12 inhibitor for acute coronary syndromes is Cangrelor, as it is the only intravenous P2Y12 receptor antagonist available 2, 3, 4.
• Cangrelor has a rapid onset of action, providing potent platelet inhibition exceeding 90%, and its antiplatelet effect subsides within 60 to 90 minutes due to its rapid metabolism by endothelial endonucleotidase 2.
• Cangrelor may be considered in P2Y12 receptor inhibitor-naïve patients undergoing percutaneous coronary intervention in both acute and stable settings, according to current guidelines 2.
• The use of Cangrelor is particularly beneficial in patients with ST-segment elevation myocardial infarction, those treated with opioids, with mild therapeutic hypothermia, or in cardiogenic shock, as it overcomes the limitations of oral P2Y12 receptor inhibitors in these settings 2, 4.

Clinical Use and Considerations

• Cangrelor is characterized by linear, dose-dependent pharmacokinetics, allowing for predictable and potent platelet inhibition 2.
• The transition from Cangrelor to an oral P2Y12 receptor antagonist is mandatory following Cangrelor infusion discontinuation, with ticagrelor being a suitable option for early administration without pharmacodynamic interaction 4.
• The clinical role of Cangrelor in conjunction with prasugrel or ticagrelor remains unclear and requires further investigation 4.
• Ongoing studies and real-life experience are expected to improve our understanding of Cangrelor's role in everyday clinical practice 4.