Cangrelor in Patients With Coronary Artery Disease Pretreated With Ticagrelor: The Switching Antiplatelet (SWAP)-5 Study.
cangrelor
pharmacodynamic
pharmacokinetic
platelets
switching
ticagrelor
Journal
JACC. Cardiovascular interventions
ISSN: 1876-7605
Titre abrégé: JACC Cardiovasc Interv
Pays: United States
ID NLM: 101467004
Informations de publication
Date de publication:
09 01 2023
09 01 2023
Historique:
received:
02
10
2022
revised:
20
10
2022
accepted:
20
10
2022
pubmed:
2
11
2022
medline:
7
1
2023
entrez:
1
11
2022
Statut:
ppublish
Résumé
There are no studies specifically designed to rule out a drug-drug interaction (DDI) when cangrelor is used among patients who have been pretreated with ticagrelor. This study sought to rule out a DDI among cangrelor-treated patients who have been pretreated with ticagrelor. In this prospective, randomized, double-blind, placebo-controlled, crossover, pharmacokinetic (PK) and pharmacodynamic (PD) study, patients with coronary artery disease (N = 20) were pretreated with a 180-mg ticagrelor loading dose and after 1 hour randomized to placebo or cangrelor (bolus and infusion for 2 hours). Patients crossed over after 1 to 4 weeks of washout. PK analysis included ticagrelor plasma levels and its active metabolite. PD assessments included VerifyNow P2Y Compared with placebo, adding cangrelor to patients pretreated with ticagrelor resulted in a significant reduction in PRU at 30 minutes and 1 hour after starting infusion. At 2 hours after stopping cangrelor/placebo infusion, PRU were low and similar in both groups (16.9 vs 12.6; mean difference: 4.3; 95% CI: -28.6 to 37.3), meeting the noninferiority primary endpoint (predefined noninferiority margin 45 PRU). Consistent findings were shown with all PD assays. PK tracked PD findings with no differences between groups in plasma levels of ticagrelor and its metabolite. Compared with placebo, the use of cangrelor in patients pretreated with ticagrelor results in enhanced platelet inhibition with no differences in PK/PD profiles after discontinuation of drug infusion indicating the absence of a DDI. (PD and PK Profiles of Switching Between Cangrelor and Ticagrelor Following Ticagrelor Pre-treatment [SWAP-5]; NCT04634162).
Sections du résumé
BACKGROUND
There are no studies specifically designed to rule out a drug-drug interaction (DDI) when cangrelor is used among patients who have been pretreated with ticagrelor.
OBJECTIVES
This study sought to rule out a DDI among cangrelor-treated patients who have been pretreated with ticagrelor.
METHODS
In this prospective, randomized, double-blind, placebo-controlled, crossover, pharmacokinetic (PK) and pharmacodynamic (PD) study, patients with coronary artery disease (N = 20) were pretreated with a 180-mg ticagrelor loading dose and after 1 hour randomized to placebo or cangrelor (bolus and infusion for 2 hours). Patients crossed over after 1 to 4 weeks of washout. PK analysis included ticagrelor plasma levels and its active metabolite. PD assessments included VerifyNow P2Y
RESULTS
Compared with placebo, adding cangrelor to patients pretreated with ticagrelor resulted in a significant reduction in PRU at 30 minutes and 1 hour after starting infusion. At 2 hours after stopping cangrelor/placebo infusion, PRU were low and similar in both groups (16.9 vs 12.6; mean difference: 4.3; 95% CI: -28.6 to 37.3), meeting the noninferiority primary endpoint (predefined noninferiority margin 45 PRU). Consistent findings were shown with all PD assays. PK tracked PD findings with no differences between groups in plasma levels of ticagrelor and its metabolite.
CONCLUSIONS
Compared with placebo, the use of cangrelor in patients pretreated with ticagrelor results in enhanced platelet inhibition with no differences in PK/PD profiles after discontinuation of drug infusion indicating the absence of a DDI. (PD and PK Profiles of Switching Between Cangrelor and Ticagrelor Following Ticagrelor Pre-treatment [SWAP-5]; NCT04634162).
Identifiants
pubmed: 36317958
pii: S1936-8798(22)02005-2
doi: 10.1016/j.jcin.2022.10.034
pii:
doi:
Substances chimiques
Ticagrelor
GLH0314RVC
cangrelor
6AQ1Y404U7
Platelet Aggregation Inhibitors
0
Purinergic P2Y Receptor Antagonists
0
Banques de données
ClinicalTrials.gov
['NCT04634162']
Types de publication
Randomized Controlled Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
36-46Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Funding Support and Author Disclosures The present study was funded by an investigator-initiated grant from The Scott R. MacKenzie Foundation. The Scott R. MacKenzie Foundation had no role in the study design conception, conduct of the study, or decision to publish these results. Dr Franchi has received consulting fees or honoraria from AstraZeneca, Bayer, and Sanofi; and has received institutional payments for grants from PLx Pharma and The Scott R. MacKenzie Foundation. Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Daiichi Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Novartis, PhaseBio, PLx Pharma, Pfizer, and Sanofi; and has received research grants to the institution from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co, Merck, Novartis, and The Scott R. MacKenzie Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.