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Relationship between clopidogrel-induced platelet P2Y12 inhibition and stent thrombosis or myocardial infarction
Christoph Varenhorst1, Sasha Koul, David Erlinge
1Uppsala Clinical Research Center, Department of Medical Sciences, Cardiology, Uppsala University, Sweden. christoph.varenhorst@ucr.uu.se
Insights
High on-clopidogrel platelet reactivity, measured by P2Y12 reaction units (PRU), is linked to stent thrombosis (STh). However, platelet function testing may not reliably identify patients at high risk for STh.
Area of Science:
- Cardiovascular medicine
- Pharmacology
- Interventional cardiology
Background:
- Stent thrombosis (STh) is a serious complication following percutaneous coronary intervention (PCI).
- Insufficient platelet inhibition is a key factor contributing to STh, but its causes are complex.
- Understanding on-clopidogrel platelet reactivity is crucial for managing patients at risk for STh and myocardial infarction (MI).
Purpose of the Study:
- To investigate on-clopidogrel platelet reactivity in patients who experienced STh after PCI.
- To compare platelet reactivity between patients with STh, MI, and control groups.
- To evaluate the utility of platelet function assays in predicting STh risk.
Main Methods:
- A case-control study using the Swedish Coronary Angiography and Angioplasty Registry.
- Inclusion of patients with angiographically confirmed STh or MI within 6 months of PCI on dual antiplatelet therapy.
- Measurement of on-clopidogrel platelet reactivity using VerifyNow P2Y12 and VASP phosphorylation assays.
Main Results:
- Patients with STh exhibited significantly higher P2Y12 reaction units (PRU) compared to controls (246.8 vs. 200.0, P = .001).
- An optimal cutoff of ≥222 PRU was identified for STh prediction (AUC 0.69, P < .0001), with 70.2% sensitivity and 67.3% specificity.
- No significant difference in PRU was observed between MI patients and controls, though device-reported percent inhibition was higher in MI patients.
Conclusions:
- High on-clopidogrel platelet reactivity, as measured by VerifyNow (PRU ≥222), is associated with STh.
- Spontaneous MI in stented patients on clopidogrel was not linked to high platelet reactivity.
- Significant overlap in platelet reactivity between STh and non-STh patients questions the clinical utility of platelet function testing for STh risk stratification.
Background:
Insufficient platelet inhibition is a major determinant of stent thrombosis (STh), although the etiology is multifactorial. On-clopidogrel platelet reactivity was investigated in patients with previous angiographically confirmed STh, myocardial infarction (MI), and controls.
Methods:
Using the Swedish Coronary Angiography and Angioplasty Registry, we identified patients with angiographically confirmed STh (n = 48) or MI (n = 30) while on dual antiplatelet therapy within 6 months of percutaneous coronary intervention (PCI) and matched control patients (n = 78). On-clopidogrel platelet reactivity was measured with VerifyNow P2Y12 and vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay.
Results:
The mean P2Y12 reaction units (PRU) was higher (246.8 ± 75.9 vs 200.0 ± 82.7, P = .001) in STh patients compared with controls. The optimal cutoff for STh was 222 PRU or higher (area under the curve 0.69, P < .0001) in a receiver operating characteristics (ROC) analysis. The cutoff level resulted in 70.2% sensitivity and 67.3% specificity. There was no significant difference in mean PRU but a higher device-reported percent inhibition (45.1 ± 23.8 vs 32.1 ± 23.2, P = .04) in patients with MI compared with controls. Results with the VASP phosphorylation assay were not related to the occurrence of STh or MI.
Conclusions:
STh was associated with high on-clopidogrel platelet reactivity measured with VerifyNow (cutoff level of PRU ≥222) but spontaneous MI in stented patients on clopidogrel treatment was not. There was, however, a substantial overlap in on-clopidogrel platelet reactivity between patients with and without on-treatment STh questioning the clinical use of platelet function testing to identify patients at high risk for STh.
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