Suboptimal response to clopidogrel and the effect of prasugrel in acute coronary syndromes

Background: High on clopidogrel platelet reactivity (HPR) has been associated with adverse outcomes following acute coronary syndromes (ACS). This study investigated the rate of HPR in a New Zealand ACS population and examined the effectiveness of prasugrel in reducing platelet reactivity in those with HPR. Methods: In this prospective cohort study, 250 patients with ACS were pretreated with aspirin and clopidogrel and residual platelet reactivity was measured using whole blood multiple electrode platelet aggregometry. Twenty-seven of the patients with HPR were treated with prasugrel at the discretion of their physician, and platelet reactivity retested. Results: Ninety-five patients (38%) had HPR. Maori and Pacific Island patients had a higher rate of HPR compared to Europeans (57% versus 35.9%, p=0.013). Additionally, patients with diabetes were also found to have higher rate of HPR compared to non-diabetics (50% versus 34.8%, p=0.045). Patients treated with a low dose clopidogrel regimen had significantly higher rates of HPR (45.4%) compared to those treated with intermediate (25.4%) or high dose regimens (26.8%, p=0.009). All of the 27 patients with HPR who were subsequently treated with prasugrel (60 mg) had a significant decrease in platelet reactivity (660 AU*min (565-770) before versus 230 AU*min (110-345) after, p<0.001), and was reduced to below the HPR cutoff in 24 (88.9%) of the patients. Conclusions: Ethnicity, diabetes and clopidogrel dose contributed to HPR. The use of prasugrel in those with HPR resulted in a consistent and marked reduction in platelet reactivity. (C) 2012 Elsevier Ireland Ltd. All rights reserved.