Obesity and a history of low response to clopidogrel treatment are predictors for a reduced antiplatelet action of prasugrel treatment

Abstract

Background: Insufficient P2Y12 receptor inhibition is associated with a higher risk for thrombotic events after PCI. The 3rd 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 PCI treated patients on prasugrel maintenance dose (MD) treatment. Methods: In a registry of PCI-treated patients (n=165, recruited between August 2009 and March 2012) on prasugrel MD treatment, the ADP-induced platelet aggregation (PA, in AU x min) was assessed on a Multiplate analyzer. Results: Seventy one (43%) from the 165 patients in this registry received prasugrel treatment following a switch over from clopidogrel treatment due to measured clopidogrel low responsiveness and 94 (57%) patients were on prasugrel MD treatment due to a prior PCI in the setting of an ACS. The ADP-induced platelet aggregation (median [IQR]) on prasugrel MD treatment was 206 [140-328] AU x min. Obese (defined by a body mass index (BMI) ≥ 30) patients (n=42) (303 [192-467] vs. 187 [120-303] AU x min, p<0.001), patients (n=71) with a history of clopidogrel low responsiveness (272 [162-409] vs. 193 [128-280] AU x min; p=0.002) and patients (n=18) on a low (5 mg) prasugrel MD (483 [252-798] vs. 198 [134-313] AU x min; p<0.001) showed higher PA values on prasugrel MD as compared to the remaining patients. In a multivariable linear regression model (including age, smoking, gender, BMI, diabetes, history of clopidogrel low responsiveness and a low (5 mg) prasugrel MD as independent variables), BMI (p=0.02), low response to clopidogrel (p=0.04) and a low prasugrel MD (p<0.001) were independently associated with higher PA values on prasugrel MD treatment, whereas the remaining variables were not (p≥0.20). Conclusion: Response variability is observed on prasugrel MD treatment. Obesity and a history of clopidogrel low responsiveness are independent predictors of an attenuated response to prasugrel treatment. Further studies are needed to explore clinical implications of this observation.