Platelet function profiles in the elderly: Results of a pharmacodynamic study in patients on clopidogrel therapy and effects of switching to prasugrel 5 mg in patients with high platelet reactivity.

Studies specifically designed to assess clopidogrel response in theelderly as well as treatment alternatives to improve platelet inhibitionin this high-risk population are lacking. This study aimed to define pharmacodynamic(PD) profiles, including high platelet reactivity (HPR)rates, among elderly patients on maintenance clopidogrel therapy andto assess the PD effects of prasugrel 5 mg/day in elderly with HPR. Thiswas a prospective observational PD study enrolling consecutive≥75-year-old patients on maintenance clopidogrel therapy (75 mg/day)who were tested for clopidogrel response by the VerifyNow P2Y12assay and light transmittance aggregometry (LTA). HPR rates were estimatedusing multiple definitions. HPR patients identified by the VerifyNowP2Y12 assay [P2Y12 reaction unit (PRU) ≥230] were switchedto prasugrel 5 mg/day, and platelet function testing was performedafter 15 days of treatment. PD testing was completed in 100 patients.The HPR prevalence varied between 25% and 32%, depending on thedefinition used. A PRU ≥230 was observed in 25 patients; of these, 20switched to prasugrel 5 mg/day. This resulted in significant reduction inPRU mean values (279.8 ± 45.1 vs. 171.7 ± 65.2, p=0.0002) with an absolutebetween-treatment difference of 108.1 (95% confidence intervals75.2–140.9). Accordingly, switching to prasugrel 5 mg/day overcameHPR in most (80%) patients. Consistently, all LTA measures weresignificantly lower after prasugrel compared with clopidogrel. In conclusion,a considerable proportion of elderly patients exhibit HPR whileon standard clopidogrel therapy. Switching to 5 mg/day prasugrel in elderly patients with HPR is associated with enhanced platelet inhibition and overcomes HPR in the majority of these patients.