Suboptimal response to clopidogrel and the effect of prasugrel in acute coronary syndromes
L R Johnston1, P D Larsen, A C La Flamme
1Victoria University of Wellington, Wellington, New Zealand.
Insights
High clopidogrel platelet reactivity (HPR) affects acute coronary syndrome (ACS) patients. Prasugrel effectively reduced platelet reactivity in 88.9% of HPR patients, indicating its therapeutic potential in this high-risk group.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Medicine
Background:
- High on clopidogrel platelet reactivity (HPR) is linked to adverse outcomes in acute coronary syndromes (ACS).
- Investigated HPR prevalence in New Zealand ACS patients.
- Assessed prasugrel's efficacy in reducing platelet reactivity in HPR patients.
Purpose of the Study:
- To determine the rate of HPR in a New Zealand ACS population.
- To evaluate the effectiveness of prasugrel in mitigating HPR.
- To identify factors contributing to HPR.
Main Methods:
- Prospective cohort study of 250 ACS patients pretreated with aspirin and clopidogrel.
- Platelet reactivity measured using whole blood multiple electrode platelet aggregometry.
- 27 HPR patients received prasugrel, with subsequent platelet reactivity retesting.
Main Results:
- 38% of patients exhibited HPR.
- Maori, Pacific Island, and diabetic patients showed higher HPR rates.
- Low-dose clopidogrel regimens were associated with significantly higher HPR.
- Prasugrel treatment in 27 HPR patients led to a significant reduction in platelet reactivity (p<0.001), with 88.9% achieving reactivity below the HPR cutoff.
Conclusions:
- Ethnicity, diabetes, and clopidogrel dosage are significant contributors to HPR.
- Prasugrel effectively and consistently reduces platelet reactivity in ACS patients with HPR.
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.
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