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A narrow therapeutic window of platelet P2Y12 reactivity in high-risk Chinese percutaneous coronary intervention
Liying Gong1,2, Yaxin Liu1, Jingle Li3
1Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China.
Insights
High-risk Chinese patients undergoing PCI have a narrow therapeutic window for P2Y12 receptor inhibition, balancing ischemic and bleeding risks. Optimizing this window is key for personalized antiplatelet therapy.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Research
Background:
- P2Y12 receptor inhibition has a known therapeutic window associated with ischemic and bleeding events.
- A defined therapeutic window for high-risk stratification after percutaneous coronary intervention (PCI) is currently lacking.
- This study investigates the P2Y12 receptor inhibition therapeutic window in high-risk Chinese PCI patients.
Purpose of the Study:
- To investigate the therapeutic window of P2Y12 receptor inhibition in high-risk Chinese patients undergoing PCI.
- To correlate vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI) values with ischemic and bleeding events.
- To identify optimal VASP-PRI cutoffs for predicting ischemic and bleeding risks.
Main Methods:
- Observational study of 860 high-risk Chinese PCI patients.
- Primary endpoint: correlation between VASP-PRI and bleeding/ischemic components.
- Secondary endpoint: composite of major adverse cardiovascular events at 12 months.
Main Results:
- VASP-PRI significantly discriminated between patients with and without ischemic events (AUC: 0.77), with an optimal cutoff of ≥ 0.45.
- VASP-PRI also significantly discriminated between patients with and without bleeding events (AUC: 0.77), with an optimal cutoff of ≤ 0.24.
- VASP-PRI was an independent predictor of major adverse cardiovascular events (OR: 10.67).
Conclusions:
- High-risk Chinese PCI patients exhibit a narrow therapeutic window for P2Y12 inhibition.
- Optimal platelet reactivity within this window reduces risks of both ischemic and bleeding events.
- Platelet reactivity measurements hold significant implications for tailoring antiplatelet therapy in high-risk populations.
Background:
Much evidence has been provided that a therapeutic window of P2Y12receptor inhibition exists, which is highly significantly associated with ischemic and bleeding events. The therapeutic window for high-risk stratification after percutaneous coronary intervention (PCI) is lacking. We aimed to investigate the therapeutic window of P2Y12receptor inhibition in high-risk Chinese PCI patients.
Methods:
In this observational study, we analyzed 860 high-risk patients who were undergoing PCI. The primary endpoint was the correlation between vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI) values with bleeding and ischemic components in high-risk patients. The secondary endpoint was a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, urgent revascularization, and stroke at 12 months after the index procedure.
Results:
Among high-risk patients, VASP-PRI could significantly discriminate between PCI patients with and without ischemic events (area under the curve (AUC): 0.77; 95% CI [0.72-0.82]; P < 0.001). A VASP-PRI ≥ 0.45 was the optimal cutoff point to predict ischemic events (sensitivity: 86.6%; specificity: 63.6%). Similarly, VASP-PRI could also significantly discriminate between PCI patients with and without bleeding events ((AUC): 0.77; 95% CI [0.73-0.81]; P < 0.001). A VASP-PRI ≤ 0.24 was the optimal cutoff point to predict bleeding events (sensitivity: 72.1%; specificity: 70.3%). Multivariate analysis showed that VASP-PRI was an independent predictor of the risk of major adverse cardiovascular events (odds ratio: 10.67, 95% CI [3.78-30.08]).
Conclusion:
Our results suggest that high-risk Chinese PCI patients have a narrow therapeutic window. Within this window, high-risk patients are at lower risk for both ischemic and bleeding events. Platelet reactivity may have significant implications for personalized antiplatelet therapy in high-risk patients.
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