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

BackgroundHigh 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.MethodsIn 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.ResultsNinety-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.ConclusionsEthnicity, 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.