title: Evidence-Based Choice of P2Y12 Inhibitors in End Stage Renal Disease Patients: A Mini-Review.
abstract: Chronic kidney disease has been identified as an independent cardiovascular risk factor. The morbidity and mortality due to cardiovascular disease are higher among chronic kidney disease patients when compared with patients with normal kidney function. Although P2Y12 inhibitors (eg. clopidogrel) are associated with increased survival rates after a myocardial infarction, most of the clinical trials excluded End-Stage Renal Disease (ESRD) patients. Besides, non-responders to P2Y12 inhibitors have been identified as at risk of cardiovascular adverse events and non-responder prevalence is higher among ESRD than in any other population. Recent data questioned the benefits from P2Y12 inhibitors among chronic kidney disease patients. This systematic review aimed to describe pharmacokinetics (PK) and pharmacodynamics (PD) evidence data among 3 widely prescribed P2Y12 inhibitors. Clopidogrel and prasugrel are bioactivated by the cytochromes P450 (CYP) while ticagrelor is already active. PD data used different assays among which the VerifyNow® which showed intravariability before and after dialysis. The potential explanation of modulated PK/PD parameters among ESRD patients will be addressed. Absorption as well as metabolism is diminished in ESRD patients. It could potentially lead to absence of clopidogrel or prasugrel bioactivation or ticagrelor accumulation. Evidence-based recommendation regarding the best option for antiaggregation secondary to percutaneous intervention in this high risk population is still lacking.
authors.forename: Yassine
authors.initials: Y
authors.lastname: Bouatou
authors.forename: Caroline Flora
authors.initials: CF
authors.lastname: Samer
authors.forename: Pierre
authors.initials: P
authors.lastname: Fontana
authors.forename: Youssef
authors.initials: Y
authors.lastname: Daali
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Rue Gabrielle Perret- Gentil 4, 1211 Geneva 14, Switzerland. jules.desmeules@hcuge.ch.
authors.forename: Jules
authors.initials: J
authors.lastname: Desmeules
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D000077144:Clopidogrel; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000068799:Prasugrel Hydrochloride / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D058921:Purinergic P2Y Receptor Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine