Predictors of antiplatelet response to prasugrel during maintenance treatment

Abstract

Insufficient P2Y12 receptor inhibition is associated with a higher risk of thrombotic events after percutaneous coronary intervention (PCI). The third generation thienopyridine prasugrel achieves stronger platelet inhibition as compared to its predecessor clopidogrel. Little is known about predictors of prasugrel drug responsiveness. The aim of this study was to explore predictors of prasugrel responsiveness in patients with a recent PCI on prasugrel maintenance dose (MD) treatment. In a registry of PCI-treated patients (n = 163, recruited between August 2009 and March 2012) on prasugrel MD treatment, the ADP-induced platelet aggregation (PA) was assessed on a Multiplate analyzer. The mean (interquartile range (IQR)) ADP-induced PA on prasugrel MD treatment was 206 (138–331) AU × min. Obese (defined by a body mass index (BMI) ≥ 30) patients (n = 42) (303 [192–467] vs. 187 [117–305] AU × min, p = 0.0001), patients (n = 70) with a history of clopidogrel low responsiveness (278 [161–409] vs. 192 [126–282] AU × min, p = 0.002) and patients (n = 18) on a low (5 mg) prasugrel MD (483 [252–798] vs. 198 [133–313] AU × min; p = 0.0001) showed higher PA values on prasugrel MD as compared to the remaining patients. In a multivariable linear regression model, the latter three variables were independently associated with higher PA values on prasugrel MD treatment. In summary response variability is observed in patients on prasugrel MD treatment. Obesity, a history of clopidogrel low responsiveness and a reduced prasugrel MD of 5 mg are independent predictors of an attenuated response to prasugrel treatment. Further studies are needed to explore clinical implications of this observation.

• Clopidogrel
• high on-treatment platelet reactivity
• obesity
• prasugrel
• prasugrel responsiveness

Declaration of interest

Supported by the DZHK (German Centre for Cardiovascular Research) and by the BMBF (German Ministry of Education and Research).

Dr. Sibbing reports receiving speaker fees from Daiichi Sankyo and Roche and fees for advisory board activities from Verum Diagnostica and Eli Lilly. Prof. Schunkert reports receiving speaker fees from Sanofi-Aventis and Daiichi Sankyo and grants from Bristol-Myers Squibb. Prof. Kastrati reports receiving lecture fees and fees for advisory board meetings from Abbott, Astra Zeneca, Biosensors, Daiichi Sankyo, Biotronik, Bristol-Meyers Squibb, MSD, The Medicines, St. Jude Medical. There is no conflict of interest for the other authors.