Cangrelor: A Potential Antiplatelet Game Changer
Cangrelor is an intravenous antiplatelet agent with ideal properties for coronary intervention, offering rapid onset, reversible offset, and minimal bleeding risk compared to GPIs and oral P2Y12 inhibitors. Its pharmacology, efficacy, and safety profile make it a promising option in managing cardiovascular conditions.
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Presentation Transcript
Cangrelor: Friend or Foe? Pro: Antiplatelet Game Changer Steven P. Dunn, PharmD, BCCP, FAHA, FCCP Lead Pharmacist, Heart & Vascular University of Virginia Health System Charlottesville, Virginia
Disclosures No significant disclosures
Idea Properties of an Antiplatelet Agent in Coronary Intervention Ideal Properties Cangrelor Intravenous Rapid onset Non organ-dependent elimination Reversible/rapid offset Highly effective Minimal risk of bleeding Low drug-drug interactions
Whats wrong with Glycoprotein IIb/IIIa Inhibitors (GPIs) High-risk of bleeding Organ dependent elimination (kidneys) Hematologic toxicities (thrombocytopenia)
Whats wrong with Oral P2Y12 Inhibitors? Suboptimal platelet inhibition (clopidogrel) 50-60% of ADP-mediate platelet aggregation Slow onset (relatively) limiting in STEMI and ad-hoc PCI Irreversible 5-7 days before near-normal platelet function upon discontinuation (slightly shorter with ticagrelor) Potential for hematologic toxicities and allergic reactions No IV formulation Drug-drug interactions (e.g., morphine affecting GI transit) Wide variability in response (less so with prasugrel/ticagrelor)
Cangrelor - Pharmacology Reversible inhibitor of the P2Y12 receptor Half-life: 3-6 minutes Dosing: IV: 30 mcg/kg bolus followed by 4 mcg/kg/min for either 2 hours or full duration of procedure if > 2 hours Elimination: primarily biliary Onset/Offset Adverse effects: bleeding, allergy Kangreal product labeling
Cangrelor Efficacy CHAMPION-PHOENIX N Engl J Med. 2013 Apr 4;368(14):1303-13
Cangrelor Efficacy vs. GPI Pooled Analysis of all CHAMPION trials Propensity-matched cohort End-point N (%) Cangrelor only (n=1021) Clopidogrel + GPI (n=1021) OR (95% CI) P-value Composite death/MI/IDR/ST 27 (2.6) 34 (3.3) 0.79 (0.48-1.32) 0.37 Death 2 (0.2) 4 (0.4) 0.50 (0.09-2.73) 0.42 MI 21 (2.1) 25 (2.4) 0.84 (0.47-1.50) 0.56 IDR 3 (0.3) 8 (0.8) 0.38 (0.10-1.41) 0.15 ST 1 (0.1) 6 (0.6) 0.17 (0.02-1.38) 0.10 JAMA Cardiol. 2017 Feb 1;2(2):127-135
Cangrelor Safety CHAMPION-PHOENIX Safety non-CABG- related bleeding Cangrelor (n=5472) Clopidogrel (n=5470) Odds Ratio (95% CI) P-value GUSTO Severe or moderate 31 (0.6) 19 (0.3) 1.63 (0.92-2.90) 0.09 TIMI Major Major or minor 5 (0.1) 14 (0.3) 5 (0.1) 8 (0.1) 1.00 (0.29-3.45) 1.75 (0.73-4.18) >0.99 0.20 Any transfusion 25 (0.5) 16 (0.3) 1.56 (0.83-2.93) 0.16 N Engl J Med. 2013 Apr 4;368(14):1303-13
Cangrelor Safety Pooled Analysis of all CHAMPION trials Propensity-matched cohort Safety N(%) Cangrelor (n=1021) Clopidogrel + GPI (n=1021) Odds Ratio (95% CI) P-value GUSTO Severe or moderate 12 (1.2) 23 (2.3) 0.50 (0.24-1.03) 0.06 TIMI Major Major or minor 2 (0.2) 7 (0.7) 8 (0.8) 24 (2.4) 0.25 (0.05-1.18) 0.29 (0.13-0.68) 0.08 0.004 Any transfusion 10 (1.0) 21 (2.1) 0.45 (0.20-0.99) 0.05 JAMA Cardiol. 2017 Feb 1;2(2):127-135
Cangrelor - Unknowns Direct, randomized comparison with newer generation P2Y12 inhibitors Would they really be more effective than clopidogrel + GPI? Cost-effectiveness analysis Direct medical costs similar between groups in CHAMPION-PHOENIX (Value in Health; 18 (2015) A1 A307)
Cangrelor Place in Therapy Strongest indications: STEMI PCI unable to swallow medications or dysfunctional gut (e.g., therapeutic hypothermia) Ad-hoc PCI during diagnostic coronary angiography Bridge therapy at reduced dose (0.75 mcg/kg/min)
Conclusions Is cangrelor an antiplatelet game changer ? Undoubtedly! Ideal procedural agent given rapid onset/offset, reversibility Oral P2Y12 still important for transition, chronic treatment IV GPI use minimal with highly effective ADP antagonist therapy
