No drug-drug interaction after switch from ticagrelor to cangrelor in stable CAD
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CHICAGO — Cangrelor infusion in adults with CAD pretreated with ticagrelor was associated with enhanced platelet inhibition compared with placebo, with no observed drug-drug interactions in the cangrelor group, researchers reported.
“We know the current label for the use of cangrelor is for patients who have not been pretreated with an oral P2Y12 inhibitor,” Dominick J. Angiolillo, MD, PhD, FACC, FESC, FSCAI, professor of medicine, chief of the division of cardiology and medical director at UF Health Cardiovascular Center and the University of Florida College of Medicine-Jacksonville, told Healio. “However, in real-world clinical practice, particularly in high-risk settings such as STEMI, many patients are pretreated. We know that the effects of an oral drug are typically delayed, which can be further exacerbated in the setting of STEMI or with the use of morphine products. There are no data evaluating the impact of cangrelor on patients pretreated with ticagrelor and to rule out a drug-drug interaction.”
For the prospective Switching Antiplatelet Therapy-5 (SWAP-5) study, Angiolillo and colleagues analyzed data from 20 adults with stable CAD pretreated with a 180-mg ticagrelor (Brilinta, AstraZeneca) loading dose and then a bolus and infusion of cangrelor (Kengreal, Chiesi) or placebo after 1 hour. Participants crossed over after a 1-to-4-week washout period. For the pharmacokinetic analysis, researchers assessed ticagrelor plasma levels and its active metabolite. For the pharmacodynamic analysis, researchers assessed VerifyNow P2Y12 reaction units (PRU), light transmittance aggregometry, vasodilator-stimulated phosphoprotein and Total Thrombus-Formation Analysis System, all performed at seven time points.
The findings were presented at the American Heart Association Scientific Sessions and published in JACC: Cardiovascular Interventions.
Compared with placebo, participants pretreated with ticagrelor who then received cangrelor experienced a reduction in PRU at 30 minutes and 1 hour after starting infusion.
At 2 hours after stopping the cangrelor or placebo infusion, PRU was low and similar in both groups (cangrelor, 16.9; placebo, 12.6; mean difference, 4.3; 95% CI, –28.6 to 37.3; P = .797), meeting the noninferiority primary endpoint.
“We observed that during the infusion of cangrelor, patients had immediate and potent platelet inhibition on top of the effects achieved by ticagrelor, again confirming the additive effects,” Angiolillo said in an interview before the data was presented. “After stopping the cangrelor infusion, we did not identify any drug-drug interaction with the transition.”
The researchers also observed consistent findings for all pharmacodynamic assays. Pharmacokinetic data tracked pharmacodynamic findings with no between-group differences in plasma levels of ticagrelor and its metabolite.
“The study overall provides support to those who in clinical practice may be utilizing cangrelor among ticagrelor-treated patients,” Angiolillo told Healio. “It is important to highlight that the study was not conducted in the acute setting; patients were pretreated for just 1 hour prior to starting to bolus and infusion of cangrelor and the infusion lasted 2 hours. We obviously cannot comment on settings that fall outside of these treatment durations.”
Reference:
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Ortega-Paz LG, et al. Abstract SU1009. Presented at: American Heart Association Scientific Sessions; Nov. 5-7, 2022; Chicago (hybrid meeting).
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