High platelet reactivity on clopidogrel therapy correlates with increased coronary atherosclerosis and calcification: a volumetric intravascular ultrasound study

JACC Cardiovasc Imaging. 2012 May;5(5):540-9. doi: 10.1016/j.jcmg.2011.12.019.


Objectives: This study sought to evaluate the relationship between platelet reactivity and atherosclerotic burden in patients undergoing percutaneous coronary intervention (PCI) with pre-intervention volumetric intravascular ultrasound (IVUS) imaging.

Background: Atherosclerosis progresses by the pathologic sequence of subclinical plaque rupture, thrombosis, and healing. In this setting, increased platelet reactivity may lead to more extensive arterial thrombosis at the time of plaque rupture, leading to a more rapid progression of the disease. Alternatively, abnormal vessel wall biology with advanced atherosclerosis is known to enhance platelet reactivity. Therefore, it is possible that by either mechanism, increased platelet reactivity may be associated with greater atherosclerotic burden.

Methods: This study included patients who underwent PCI with pre-intervention IVUS imaging and platelet reactivity functional assay (P2Y(12) reaction units) performed >16 h after PCI, after the stabilization of clopidogrel therapy (administered before PCI). Platelet reactivity >230 P2Y(12) reaction units defined high on-treatment platelet reactivity (HPR).

Results: Among 335 patients (mean age 65.0 years, 71% men), there were 109 patients with HPR (32.5%) and 226 without HPR (67.5%), with HPR being associated with diabetes and chronic renal insufficiency. By IVUS analysis, patients with HPR had significantly greater target lesion calcium lengths, calcium arcs, and calcium indexes. Furthermore, patients with HPR tended to have longer lesions and greater volumetric dimensions, indicating higher plaque volume, larger total vessel volume, and also greater luminal volume, despite similar plaque burden. By multivariate analysis controlling for baseline clinical variables, HPR was the single consistent predictor of all IVUS parameters examined, including plaque volume, calcium length, and calcium arc.

Conclusions: Increased platelet reactivity on clopidogrel treatment, defined as >230 P2Y(12) reaction units, is associated with greater coronary artery atherosclerotic disease burden and plaque calcification.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary* / adverse effects
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Chi-Square Distribution
  • Clopidogrel
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / therapy*
  • Coronary Vessels / diagnostic imaging*
  • Coronary Vessels / pathology
  • Drug Resistance
  • Female
  • Humans
  • Least-Squares Analysis
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • New York City
  • Plaque, Atherosclerotic
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Function Tests
  • Predictive Value of Tests
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Receptors, Purinergic P2Y12 / blood
  • Receptors, Purinergic P2Y12 / drug effects
  • Registries
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Time Factors
  • Treatment Outcome
  • Ultrasonography, Interventional*
  • Vascular Calcification / blood
  • Vascular Calcification / diagnostic imaging
  • Vascular Calcification / therapy*


  • P2RY12 protein, human
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y12
  • Clopidogrel
  • Ticlopidine