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Published on: November 8, 2024
Intrinsic platelet reactivity before start with clopidogrel as predictor for on-clopidogrel platelet function and
Willibald Hochholzer1, Christian M Valina, Timo Bömicke
1Willibald Hochholzer, MD, Universitaets-Herzzentrum Freiburg · Bad Krozingen, Klinik für Kardiologie und Angiologie II, Suedring 15, 79189 Bad Krozingen, Germany, Tel.: +49 7633 402 0, Fax: +49 7633 402 2489,
Insights
Intrinsic platelet reactivity predicts on-clopidogrel response but doesn't predict clinical outcomes. On-treatment platelet function testing is crucial for identifying patients at risk after coronary stenting.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Medicine
Background:
- High on-clopidogrel platelet reactivity is linked to adverse clinical outcomes in patients undergoing coronary stenting.
- Intrinsic platelet reactivity, measured before treatment, may influence response to clopidogrel.
- The predictive value of intrinsic platelet reactivity for on-clopidogrel response and clinical outcomes remains unclear.
Purpose of the Study:
- To determine if intrinsic platelet reactivity can predict on-clopidogrel platelet reactivity.
- To assess if intrinsic platelet reactivity identifies patients with insufficient clopidogrel response and at risk for adverse events.
- To evaluate the association between intrinsic and on-clopidogrel platelet reactivity with long-term clinical outcomes.
Main Methods:
- Light transmission aggregometry (5 µM ADP) assessed platelet reactivity before and after clopidogrel initiation in 765 patients undergoing elective coronary stenting.
- Patients received a 600mg loading dose and a maintenance dose of clopidogrel.
- Follow-up was conducted for up to seven years, with a primary endpoint of all-cause death or non-fatal myocardial infarction.
Main Results:
- Intrinsic and on-clopidogrel platelet reactivity showed a significant correlation (r=0.31; p < 0.001).
- Intrinsic platelet reactivity was the strongest predictor of on-clopidogrel reactivity among tested factors, but explained only 8% of its variability.
- On-treatment platelet reactivity, not intrinsic reactivity, was predictive of long-term clinical outcomes (HR 1.47; p = 0.02).
Conclusions:
- Intrinsic platelet reactivity is the strongest predictor of early on-clopidogrel platelet reactivity but explains limited variability.
- Baseline intrinsic platelet reactivity is not significantly associated with long-term clinical outcomes after coronary stenting.
- On-clopidogrel platelet function testing is necessary and cannot be substituted by baseline intrinsic reactivity assessment for predicting clinical outcomes.
Abstract:
High on-clopidogrel platelet reactivity is associated with worse clinical outcome. Previous data suggest that intrinsic platelet reactivity before initiation of clopidogrel contributes significantly to on-clopidogrel platelet reactivity. It is unknown whether intrinsic reactivity can sufficiently predict on-clopidogrel reactivity and therefore identify patients with insufficient response to clopidogrel before initiation of treatment and at risk for worse clinical outcome. This analysis included 765 consecutive patients undergoing elective coronary stent implantation. Platelet reactivity was assessed by light transmission aggregometry (5 µM ADP) before administration of clopidogrel 600mg and after intake of first maintenance dose of clopidogrel on day 1 following coronary stenting. Patients were followed for up to seven years. The combined primary endpoint was death of any cause or non-fatal myocardial infarction. Intrinsic and on-clopidogrel platelet reactivity were significant correlated (r=0.31; p < 0.001). Among all tested clinical and genetic factors including the cytochrome P450 2C19*2 polymorphism, intrinsic platelet reactivity was the strongest predictor for on-clopidogrel platelet reactivity. However, intrinsic platelet reactivity could only explain 8 % of variability of on-clopidogrel platelet function. Only on-treatment platelet reactivity was predictive for long-term clinical outcome (HR 1.47, 95 % CI 1.05-2.05; p = 0.02) whereas intrinsic platelet reactivity was not (HR 1.03, 95 % CI 0.74-1.43; p = 0.86). In conclusion, intrinsic platelet reactivity before initiation of clopidogrel is the strongest predictor of early on-clopidogrel platelet reactivity but can only explain a minor proportion of its variability and is not significantly associated with clinical outcome. Thus, baseline testing cannot substitute on-clopidogrel platelet function testing.
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