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Pharmacodynamics
in STEMI
CANTIC: A pharmacodynamic study
in STEMI with KENGREAL® (cangrelor)
CANTIC study design
CANTIC is the first prospective, randomized, double-blind, placebo-controlled study to assess the comparative pharmacodynamic effects of cangrelor plus crushed ticagrelor versus crushed ticagrelor alone in STEMI patients undergoing Primary PCI (n=50; PD population=44). It also evaluated the potential for drug-drug interactions when transitioning from KENGREAL® (cangrelor) to ticagrelor in the PCI setting.1
Adding KENGREAL leads to more prompt and potent platelet inhibitory effects compared with crushed ticagrelor alone1
Even in the presence of crushed ticagrelor, KENGREAL leads to more rapid and potent P2Y12 inhibition than crushed ticagrelor alone. Significant differences were observed as early as 5 minutes post-bolus administration.1
There was no difference in PRU levels between treatment arms after discontinuation of drug infusion.
Platelet inhibition over time as measured by PRU levels1
These pharmacodynamic findings need to be interpreted with caution and do not represent adequate evidence of clinical implications. Assessment of clinically relevant endpoints warrant further investigation in an adequately powered clinical trial.
*End of PCI was 41 minutes (range 21–54 minutes) after KENGREAL/placebo bolus.
Values >208 PRU (measured by VerifyNow assay) were considered evidence of High Platelet Reactivity (HPR).2
Error bars indicate 95% confidence intervals.
KENGREAL associated with significantly reduced rates of HPR1
Compared to placebo, KENGREAL was also associated with significantly reduced rates of high on-treatment platelet reactivity (HPR) during the duration of drug infusion, which was assessed by measurements of P2Y12 Reaction Units (PRU) >208 and Platelet Reactivity Index (PRI) >50%.1
Variability in platelet inhibition
KENGREAL + crushed ticagrelor3
These pharmacodynamic findings need to be interpreted with caution and do not represent adequate evidence of clinical implications. Assessment of clinically relevant endpoints warrant further investigation in an adequately powered clinical trial.
Placebo + crushed ticagrelor3
These pharmacodynamic findings need to be interpreted with caution and do not represent adequate evidence of clinical implications. Assessment of clinically relevant endpoints warrant further investigation in an adequately powered clinical trial.
All patients in the KENGREAL group achieved a PRU <208 threshold for HPR at the first measurement (5 min), and maintained a level below threshold for the duration on the infusion. There were higher rates of HPR and more variability in platelet reactivity for individual patients treated with crushed ticagrelor alone.1
All patients were treated with both crushed ticagrelor and fentanyl.1 Fentanyl is known to interfere with absorption of oral P2Y12 inhibitors.4-6 The significance of the interaction on these pharmacodynamic findings is unknown.
Consider KENGREAL when treating complex lesions
Important Safety Information
KENGREAL® (cangrelor) for Injection is contraindicated in patients with significant active bleeding.
KENGREAL® is contraindicated in patients with known hypersensitivity (e.g., anaphylaxis) to cangrelor or any component of the product.
Drugs that inhibit platelet P2Y12 function, including KENGREAL®, increase the risk of bleeding. In CHAMPION PHOENIX, bleeding events of all severities were more common with KENGREAL® than with clopidogrel. Bleeding complications with KENGREAL® were consistent across a variety of clinically important subgroups. Once KENGREAL® is discontinued, there is no antiplatelet effect after an hour.
The most common adverse reaction is bleeding.
Indication
KENGREAL® (cangrelor) for Injection is a P2Y12 platelet inhibitor indicated as an adjunct to percutaneous coronary intervention (PCI) to reduce the risk of periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis (ST) in patients who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor.
References: 1. Franchi F, Rollini F, Rivas A, et al. Platelet inhibition with cangrelor and crushed ticagrelor in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Circulation. 2019;139:1661-1670. 2. Tantry US, Bonello L, Aradi D, et al. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol. 2013;62(24):2261–2273. 3. Supplemental Data; Franchi F, Rollini F, Rivas A, et al. Platelet inhibition with cangrelor and crushed ticagrelor in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Circulation. 2019;139:1661-1670. 4. BRILINTA® (ticagrelor) Prescribing Information. 2021. 5. EFFIENT® (prasugrel) Prescribing Information. 2019. 6. PLAVIX® (clopidogrel bisulfate) Prescribing Information. 2021. 7. KENGREAL® (cangrelor) Prescribing Information. 2020. 8. Stone GW, Généreux P, Harrington RA, et al. Impact of lesion complexity on peri-procedural adverse events and the benefit of potent intravenous platelet adenosine diphosphate receptor inhibition after percutaneous coronary intervention: core laboratory analysis from 10,854 patients from the CHAMPION PHOENIX trial. Eur Heart J. 2018;39(46):4112-4121.