Aims: Patients with diabetes mellitus (DM) and chronic kidney disease (CKD) are at increased risk of atherothrombotic events. Ticagrelor reduces ischaemic events compared to clopidogrel, with the greatest risk reduction in patients with both DM and CKD. How CKD status affects the pharmacodynamic (PD) and pharmacokinetic (PK) profiles of different ticagrelor maintenance dose regimens in patients with DM is unknown.
Methods And Results: In this randomized, crossover study, patients with DM on treatment with dual antiplatelet therapy (aspirin and clopidogrel) were stratified according to CKD status and randomized to ticagrelor 90 or 60 mg bid. PK/PD assessments were performed at baseline, after 7-10 days of ticagrelor (peak and trough), and after 7-10 days of alternative ticagrelor regimen (peak and trough). PK assessments included plasma concentrations of ticagrelor and its major metabolite. PD assessments included vasodilator-stimulated phosphoprotein (VASP)-platelet reactivity index (PRI), VerifyNow P2Y12, and light transmittance aggregometry (LTA). A total of 92 patients with DM (CKD, n = 44; non-CKD, n = 48) were randomized. Levels of platelet reactivity were lower with the 90 mg compared with the 60 mg ticagrelor dose, which was statistically significant in non-CKD but not in CKD patients for most PD measures. There were no significant differences in the primary endpoint (trough levels of VASP-PRI following ticagrelor 90 mg dosing) between cohorts (31 ± 20 vs. 25 ± 14; P = 0.105). VerifyNow and LTA provided similar findings. PK assessments tracked PD profiles showing increased plasma concentrations of ticagrelor and its major metabolite in CKD compared to non-CKD patients.
Conclusion: In patients with DM, although ticagrelor maintenance dose regimens (60 and 90 mg) yield potent P2Y12 inhibition, levels of platelet reactivity tended to be higher and subject to broader variability in non-CKD compared with CKD patients.
Clinical Trial Registration: http://www.clinicaltrials.gov Unique Identifier: NCT02539160.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/ehjcvp/pvab042 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Central Sleep Apnea and Cardiovascular Disease State-of-the-Art.
Sleep
December 2024
Midwest Cardiovascular Institute, Naperville, Illinois, USA.
Central sleep apnea (CSA), a rare polysomnographic finding in the general population, is prevalent in certain cardiovascular conditions including systolic and diastolic left ventricular dysfunction, atrial fibrillation, coronary artery disease, carotid artery stenosis, stroke and use of certain cardiac-related medications. Polysomnographic findings of CSA with adverse cardiovascular impacts include nocturnal hypoxemia and arousals, which can lead to increased sympathetic activity both at night and in the daytime. Among cardiovascular diseases, CSA is most prevalent in patients with left ventricular systolic dysfunction; a large study of more than 900 treated patients has shown a dose dependent relationship between nocturnal desaturation and mortality.
View Article and Find Full Text PDFReal-World Analyses of the De-Escalation of Dual Antiplatelet Therapy in Treatment of Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention in Taiwan.
Acta Cardiol Sin
January 2025
Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University.
Background: Dual antiplatelet therapy (DAPT) is the standard treatment for acute myocardial infarction (MI). This study aimed to investigate the use of DAPT and de-escalation after discharge in real-world practice among patients with acute MI undergoing percutaneous coronary intervention (PCI) in Taiwan.
Methods: Using the Taiwan National Health Insurance Research Database, we included patients who received PCI for acute MI and survived to discharge with DAPT from 2011 to 2021.
Intracranial hemorrhagic events associated with flow diversion treatment: a retrospective analysis from a single academic institution.
Neurosurg Rev
January 2025
Neurosurgical Service, Harvard Medical School, Beth Israel Deaconess Medical Center, 110 Francis Street, Boston, MA, 02215, USA.
Intracranial hemorrhages are highly concerning but underreported complications related to flow diversion (FD) treatment of intracranial aneurysms. Herein, we aimed to characterize these complications and the factors influencing their occurrence. We retrospectively reviewed patients treated with FD from 2013 to 2023 at a single U.
View Article and Find Full Text PDFMaintenance therapy with a P2Y12 receptor inhibitor after cangrelor in patients with acute coronary syndrome. The ELECTRA-SIRIO 2 investigators' viewpoint.
Cardiol J
January 2025
Department of Clinical and Interventional Cardiology, Sassari University Hospital, Sassari, Italy.
According to the ESC guidelines, cangrelor may be considered in P2Y12-inhibitor-naïve acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). The aim of this review is to summarize available evidence on the optimal maintenance therapy with P2Y12 receptor inhibitor after cangrelor. Transitioning from cangrelor to a thienopyridine, but not ticagrelor, can be associated with a drug-drug interaction (DDI); therefore, a ticagrelor loading dose (LD) can be given any time before, during, or at the end of a cangrelor infusion, while a LD of clopidogrel or prasugrel should be administered at the time the infusion of cangrelor ends or within 30 minutes before the end of infusion in the case of a LD of prasugrel.
View Article and Find Full Text PDFRed cell microparticles produced using high-pressure extrusion enhance both primary and secondary hemostasis.
Pharmacol Rep
January 2025
Department of Neurology, Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, 1600 NW 10th Ave RMSB #7046, Miami, FL, 33136, USA.
Background: Current therapies to treat excessive bleeding are associated with significant complications, which may outweigh their benefits. Red blood cell-derived microparticles (RMPs) are a promising hemostatic agent. Previous studies demonstrated that they reduce bleeding in animal models, correct coagulation defects in patient blood, and have an excellent safety profile.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!