Cardiovascular mortality in chronic kidney disease patients undergoing percutaneous coronary intervention is mainly related to impaired P2Y12 inhibition by clopidogrel

J Am Coll Cardiol. 2011 Jan 25;57(4):399-408. doi: 10.1016/j.jacc.2010.09.032.


Objectives: We sought to determine whether low platelet response to the P2Y(12) receptor antagonist clopidogrel as assessed by vasodilator-stimulated phosphoprotein flow cytometry test (VASP-FCT) differentially affects outcomes in patients with or without chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI).

Background: Although both CKD and impaired platelet responsiveness to clopidogrel are strong predictors of unfavorable outcome after PCI, the impact of their association is unknown. The platelet VASP-FCT assay is specific for the P2Y(12) ADP receptor pathway. In this test, platelet activation is expressed as the platelet reactivity index (PRI).

Methods: Four-hundred forty unselected patients (CKD: 126, estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m(2)), no-CKD: 314 eGFR >60 ml/min/1.73 m(2)) undergoing urgent (n = 336) or planned (n = 104) PCI were prospectively enrolled. In each subgroup, patients were classified as low-responders (LR: PRI ≥ 61%) or responders (R: PRI <61%) to clopidogrel.

Results: At a mean follow-up of 9 ± 2 months, all-cause mortality, cardiac death, and possible stent thrombosis were higher in CKD than in no-CKD patients. Within the CKD group, the LR status was associated with higher rates of all-cause mortality (25.5% vs. 2.8%, p < 0.001), cardiac death (23.5% vs. 2.8%, p < 0.001), all stent thrombosis (19.6% vs. 2.7%, p = 0.003), and MACE (33.3% vs. 12.3%, p = 0.007). Conversely, in no-CKD patients, the LR status did not affect outcomes. Multivariate analysis identified Killip class ≥ 3, drug-eluting stent implantation, and the interaction between LR and CKD (hazard ratio: 11.96, 95% confidence interval: 1.22 to 116.82; p = 0.033) as independent predictors of cardiac death.

Conclusions: In CKD patients, the presence of low platelet response to clopidogrel is associated with worse outcomes after PCI.

Publication types

  • Comparative Study

MeSH terms

  • Acute Coronary Syndrome / complications
  • Acute Coronary Syndrome / mortality*
  • Acute Coronary Syndrome / therapy
  • Aged
  • Angioplasty, Balloon, Coronary / adverse effects
  • Angioplasty, Balloon, Coronary / mortality*
  • Blood Platelets / drug effects
  • Cause of Death*
  • Clopidogrel
  • Cohort Studies
  • Coronary Stenosis / complications
  • Coronary Stenosis / mortality*
  • Coronary Stenosis / therapy
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Prospective Studies
  • Purinergic P2Y Receptor Antagonists / administration & dosage
  • Purinergic P2Y Receptor Antagonists / adverse effects*
  • Reference Values
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / diagnosis
  • Risk Assessment
  • Survival Analysis
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*


  • Purinergic P2Y Receptor Antagonists
  • Clopidogrel
  • Ticlopidine