title: Pharmacodynamic effects of standard dose prasugrel versus high dose clopidogrel in non-diabetic obese patients with coronary artery disease.
abstract: Increased body weight is independently associated with impaired clopidogrel pharmacodynamic (PD) response. Prasugrel has more potent PD effects compared with clopidogrel, although its PD effects in obese patients are unknown. The aim of this prospective, randomised, study was to compare the PD effects of standard-dose prasugrel [60 mg loading dose (LD)/10 mg daily maintenance dose (MD)] with high-dose clopidogrel (900 mg LD/150 mg daily MD) in non-diabetic obese [body mass index (BMI) ≥30 kg/m²] patients, with coronary artery disease (CAD) on aspirin therapy. PD assessments (baseline, 2 hours post-LD and 6 ± 2 days after MD) were conducted using four platelet function assays, and the platelet reactivity index (PRI) assessed by VASP was used for sample size estimation. A total of 42 patients with a BMI of 36.42 ± 5.6 kg/m² completed the study. There were no differences in baseline PD measures between groups. At 2 hours post-LD, prasugrel was associated with lower PRI compared with clopidogrel (24.3 ± 5.5 vs 58.7 ± 5.7, p≤0.001), with consistent findings for all assays. At one-week, PRI values on prasugrel MD were lower than clopidogrel MD without reaching statistical significance (34.7 ± 5.8 vs 42.9 ± 5.8, p=0.32), with consistent findings for all assays. Accordingly, rates of high on-treatment platelet reactivity were markedly reduced after prasugrel LD, but not after MD. In conclusion, in non-diabetic obese patients with CAD, standard prasugrel dosing achieved more potent PD effects than high-dose clopidogrel in the acute phase of treatment, but this was not sustained during maintenance phase treatment. Whether an intensified prasugrel regimen is required in obese patients warrants investigation.
authors.forename: Andrew
authors.initials: A
authors.lastname: Darlington
authors.forename: Antonio
authors.initials: A
authors.lastname: Tello-Montoliu
authors.forename: Fabiana
authors.initials: F
authors.lastname: Rollini
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ueno
authors.forename: José Luis
authors.initials: JL
authors.lastname: Ferreiro
authors.forename: Ronakkumar
authors.initials: R
authors.lastname: Patel
authors.forename: Bhaloo
authors.initials: B
authors.lastname: Desai
authors.forename: Luis A
authors.initials: LA
authors.lastname: Guzman
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Bass
authors.affiliation: Dominick J. Angiolillo MD, PhD, University of Florida College of Medicine-Jacksonville, 655 West 8th Street, Jacksonville, FL 32209, USA, Tel: +1 904 244 3933, Fax: +1 904 244 3102, E-mail: dominick.angiolillo@jax.ufl.edu.
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
mesh_terms: D001241:Aspirin / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015992:Body Mass Index; D015815:Cell Adhesion Molecules / Q000097:blood; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005431:Florida; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000175:diagnosis; D010750:Phosphoproteins / Q000097:blood; D010766:Phosphorylation; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D015539:Platelet Activation / Q000187:drug effects*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride; D011446:Prospective Studies; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C548576:P2RY12 protein, human; D010750:Phosphoproteins; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D013876:Thiophenes; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin
keywords: Platelet function; clopidogrel; coronary artery disease; obesity; prasugrel