Pharmacodynamic effects of standard dose prasugrel versus high dose clopidogrel in non-diabetic obese patients with coronary artery disease

Andrew Darlington; Antonio Tello-Montoliu; Fabiana Rollini; Masafumi Ueno; José Luis Ferreiro; Ronakkumar Patel; Bhaloo Desai; Luis A. Guzman; Theodore A. Bass; Dominick Angiolillo

doi:10.1160/TH13-07-0529

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2014; 111(02): 258-265
DOI: 10.1160/TH13-07-0529

Platelets and Blood Cells

Schattauer GmbH

Pharmacodynamic effects of standard dose prasugrel versus high dose clopidogrel in non-diabetic obese patients with coronary artery disease

Authors

Andrew Darlington

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
Antonio Tello-Montoliu

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
Fabiana Rollini

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
Masafumi Ueno

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
José Luis Ferreiro

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
Ronakkumar Patel

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
Bhaloo Desai

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
Luis A. Guzman

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
Theodore A. Bass

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
Dominick Angiolillo

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA

Abstract

Summary

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 highdose 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.

Keywords

Platelet function - obesity - coronary artery disease - prasugrel - clopidogrel

Full Text

References

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