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Clopidogrel response variability is associated with endothelial dysfunction in coronary artery disease patients

Gerasimos Siasos1, Evangelos Oikonomou2, Marina Zaromitidou1

  • 11st Department of Cardiology, 'Hippokration' Hospital, University of Athens Medical School, Athens, Greece; Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Atherosclerosis
|July 20, 2015
PubMed

Insights

Endothelial dysfunction is linked to varied responses to clopidogrel in patients after percutaneous coronary intervention (PCI). This finding helps explain why some patients have suboptimal platelet inhibition despite dual antiplatelet therapy.

Area of Science:

  • Cardiovascular Medicine
  • Pharmacology
  • Clinical Research

Background:

  • Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is standard after percutaneous coronary intervention (PCI).
  • Variability in clopidogrel response can be influenced by clinical and genetic factors.
  • The role of endothelial dysfunction in clopidogrel response variability post-PCI remains unclear.

Purpose of the Study:

  • To investigate the impact of endothelial dysfunction on clopidogrel response variability.
  • To assess the relationship between endothelial function and platelet reactivity in stable coronary artery disease (CAD) patients post-PCI.

Main Methods:

  • 198 patients with stable CAD one month post-PCI on DAPT (clopidogrel 75 mg, aspirin 100 mg) were enrolled.
  • Platelet reactivity was measured using the VerifyNow P2Y12 assay (P2Y12 reaction units, PRU).
  • Endothelial function was assessed via flow-mediated dilation (FMD).

Main Results:

  • Patients with high on-treatment platelet reactivity (HPR, 32%) exhibited significantly lower FMD values compared to those with low reactivity (4.35 ± 2.22% vs. 5.74 ± 3.29%, p=0.01).
  • An inverse correlation was observed between FMD and platelet reactivity (r=-0.24, p=0.001).
  • Multivariate analysis indicated that a 1% decrease in FMD increased the odds of HPR by 1.66 (95% CI 1.03-2.57, p=0.037), even after adjusting for confounders.

Conclusions:

  • Endothelial dysfunction is significantly associated with clopidogrel response variability in patients post-PCI on DAPT.
  • These findings suggest a potential mechanism linking endothelial health to antiplatelet therapy effectiveness.
  • Understanding this association may improve risk stratification and personalize antiplatelet treatment strategies.
Abstract

Keywords:
AtherosclerosisClopidogrelCoronary artery diseaseEndothelial functionPlatelet function testsPlatelet reactivity

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