Practice Therapeutics

Oral antiplatelet agents clopidogrel and prasugrel for the prevention of cardiovascular events

BMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d3488 (Published 17 June 2011) Cite this as: BMJ 2011;342:d3488
  1. Gabriella Passacquale, clinical research fellow,
  2. Albert Ferro, professor of cardiovascular clinical pharmacology
  1. 1Department of Clinical Pharmacology, Cardiovascular Division, King’s College London, London, London SE1 9NH, UK
  1. Correspondence to: A Ferro albert.ferro{at}kcl.ac.uk

Case scenario

A 68 year old man with hypertension, type 2 diabetes, and stable angina developed severe dyspepsia while taking aspirin. In accordance with the Joint British Societies 2 guidelines,1 his general practitioner changed the aspirin to clopidogrel 75 mg daily, with no recurrence of dyspepsia. The patient was also taking simvastatin, ramipril, metformin, and isosorbide mononitrate. Six months later he developed non-ST elevation myocardial infarction, requiring immediate insertion of a paclitaxel eluting stent. Three days later he was discharged taking prasugrel 10 mg daily (in place of clopidogrel) to continue for one year plus aspirin 75 mg daily, in addition to his other medications. He was also started on omeprazole 40 mg daily owing to his history of aspirin induced dyspepsia.

Clopidogrel and prasugrel belong to the thienopyridine family of oral antiplatelet agents and are used for cardiovascular prophylaxis. As second and third generation thienopyridines respectively, they differ in chemical structure and metabolism (figure). However, both are prodrugs, converted in vivo to active metabolites that selectively and irreversibly bind the purinergic receptor P2Y12 (receptor for adenosine diphosphate (ADP)) on platelets, thus preventing ADP dependent platelet activation.2

Pathways of metabolism for clopidogrel and prasugrel. Their metabolism is a two step process, with production of an intermediate metabolite and subsequent conversion to the active compound. For clopidogrel, this process is entirely mediated by hepatic cytochrome P450 enzymes, whereas prasugrel is initially rapidly hydrolysed by intestinal esterase (carboxylesterase 2 (hCE2)) then metabolised further by cytochrome P450 to the active molecule. Therefore, prasugrel is less dependent than clopidogrel on hepatic cytochrome P450 for its activation, resulting in the formation of more active metabolite, faster onset of action, and higher degree of in vivo platelet inhibition.3 4 The data in the table are from Farid et al4

Reversible P2Y12 …

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