Serotonergic Antidepressant Initiation is Associated with Increased Platelet Inhibition Variability After Lower...

Area of Science:

• Cardiovascular Medicine
• Pharmacology
• Vascular Surgery

Background:

• Peripheral artery disease (PAD) affects 20-37% of patients, often requiring serotonergic antidepressants alongside antiplatelet therapy post-vascular intervention.
• Platelets rely on the serotonin transporter for serotonin uptake, suggesting potential interactions between antidepressants and platelet function.
• Understanding these interactions is crucial for managing antiplatelet therapy efficacy and safety in PAD patients.

Purpose of the Study:

• To determine if serotonergic antidepressant exposure is associated with longitudinal instability in adenosine diphosphate (ADP)-mediated platelet inhibition.
• To investigate the impact of initiating, discontinuing, or stably using serotonergic agents on platelet inhibition variability.
• To explore these associations in the context of chronic limb-threatening ischemia (CLTI).

Main Methods:

• Retrospective cohort study of prospectively enrolled PAD patients undergoing lower extremity revascularization.
• Serial thromboelastography with platelet mapping (TEG-PM) data analyzed for visit-to-visit variability in ADP-mediated platelet inhibition.
• Adjusted linear mixed-effects models used to assess associations between serotonergic antidepressant exposure transitions (initiation, discontinuation, stable use) and platelet inhibition variability.

Main Results:

• Serotonergic antidepressant initiation was significantly associated with increased longitudinal variability in ADP-mediated platelet inhibition (p=0.009).
• Stable serotonergic antidepressant use was not associated with increased variability.
• Ticagrelor use was independently associated with lower platelet inhibition variability (p=0.008).

Conclusions:

• Initiation of serotonergic antidepressants, not stable therapy, is linked to increased instability in ADP-mediated platelet inhibition post-lower extremity revascularization.
• The peri-initiation window for serotonergic antidepressants is critical for medication reconciliation in vascular surgery patients.
• P2Y12 regimen consistency may influence the magnitude of medication-induced platelet instability.