Baseline P2Y12 reactivity, kidney function, and CYP2C19 genotype determine clopidogrel responsiveness in acute stroke

Area of Science:

• Cardiology
• Neurology
• Pharmacology

Background:

• Clopidogrel is a primary P2Y12 inhibitor for preventing ischemic stroke recurrence.
• Measuring platelet P2Y12 reactivity is crucial for assessing antiplatelet drug efficacy.
• High on-clopidogrel platelet P2Y12 reactivity (HCPR) may increase vascular event risk.

Purpose of the Study:

• To determine if HCPR is associated with short-term vascular events in acute stroke patients.
• To identify predictors of HCPR in patients experiencing acute stroke.
• To develop a risk score for predicting HCPR.

Main Methods:

• 190 acute stroke patients receiving clopidogrel within 12-48 hours were included.
• Platelet reactivity was measured at baseline and post-treatment using the VerifyNow system.
• Recurrent ischemic events within 21 days were the primary endpoint; multivariate analyses were performed.

Main Results:

• HCPR was significantly associated with short-term recurrent ischemic events (OR 2.5, p=0.027).
• Predictors of HCPR included high baseline reactivity, impaired kidney function, and CYP2C19 loss-of-function alleles.
• A risk score combining these factors effectively predicted HCPR (p<0.001), with higher scores indicating greater risk.

Conclusions:

• HCPR is a significant risk factor for short-term recurrent ischemic events after stroke.
• A novel risk score can predict HCPR, aiding in personalized antiplatelet therapy selection.
• This score may improve clinical decision-making for tailored antiplatelet strategies in stroke patients.