Abstract 11347: Effect of Prasugrel on Platelet Function Profiles in Non-Diabetic Obese Patients with Coronary Artery Disease
Background: Increased body weight is independently associated with impaired clopidogrel response in patients with coronary artery disease (CAD). Prasugrel has more potent antiplatelet effects compared with clopidogrel in various clinical settings. However, pharmacodynamic (PD) response profiles to prasugrel and how these compare with clopidogrel in patients with elevated body weight has not yet been explored.
Methods: This is a prospective, randomized, parallel design, PD study comparing standard dose prasugrel [60mg loading dose(LD)/10mg daily maintenance dose (MD)] with high dose clopidogrel (900mg LD/150mg daily MD) in CAD patients with obesity, defined as a body mass index (BMI) >30 kg/m2. All patients were on aspirin (81 mg/daily). Given that diabetes mellitus (DM) is also an independent predictor of impaired clopidogrel response and is frequently associated with an elevated BMI, DM patients were excluded from the study to avoid confounders and only non-DM patients were eligible for enrollment. PD assessments were conducted at 3 time-points: baseline (prior to LD), 2 hours post-LD and one week after MD. The primary endpoint was the platelet reactivity index (PRI), determined by VASP measured at one-week. Additional PD assessments included LTA following 5 and 20 μ mol/L stimuli, Multiplate Analyzer and the Verify Now P2Y12 assay.
Results: A total of 42 non-DM patients were studied (prasugrel, n=22; clopidogrel, n=20). Both groups had similar baseline characteristics with a BMI of 35.9±4.9 kg/m2 and 36.9±6.2 kg/m2 in the prasugrel and clopidogrel arms, respectively. Baseline PRI values were similar between groups. At 2 hours post-LD, PRI values reduced to a greater extent with prasugrel compared with clopidogrel (23.5±5.7% vs 59.5±5.5% p<0.001). At one-week, although prasugrel was associated with numerically lower PRI values, this was no longer statistically significant (34.3±5.3% vs 43.2±6% p=0.275). Parallel findings were observed using all other PD assays.
Conclusions: In non-DM obese patients with CAD, a standard treatment regimen of prasugrel achieved more potent PD effects than a high dosing regimen of clopidogrel in the acute phase of treatment, but this was not sustained in the maintenance phase of therapy.
- © 2012 by American Heart Association, Inc.