Beyond Linear Risk: A U-Shaped Association Between Platelet Reactivity and Mortality in Coronary Artery Disease

Area of Science:

• Cardiology
• Pharmacology
• Clinical Research

Background:

• Optimal platelet inhibition is crucial for managing thrombotic and hemorrhagic risks in coronary artery disease (CAD).
• High on-treatment platelet reactivity (HPR) is linked to adverse outcomes, but its relationship with cardiovascular mortality, particularly non-linear associations, is not fully understood.
• P2Y12 reaction units (PRU) is a key measure of platelet reactivity.

Purpose of the Study:

• To investigate the association between PRU and cardiovascular mortality in CAD patients.
• To specifically identify and characterize potential non-linear relationships between PRU and mortality risk.

Main Methods:

• Retrospective observational cohort study of 1000 CAD patients.
• Platelet reactivity assessed using the VerifyNow P2Y12 assay.
• Restricted cubic spline regression used to analyze non-linear associations between PRU and cardiovascular mortality.

Main Results:

• Linear models showed no significant association between PRU and cardiovascular mortality.
• Spline analyses revealed a significant U-shaped, non-linear relationship between PRU and mortality risk.
• Both low and high PRU levels were associated with increased mortality, while intermediate PRU levels indicated the lowest risk.

Conclusions:

• A significant non-linear association exists between platelet reactivity (PRU) and cardiovascular mortality in CAD patients.
• Both insufficient and excessive platelet inhibition increase mortality risk, highlighting an optimal intermediate therapeutic range.
• Findings support individualized antiplatelet therapy guided by platelet function testing.