Impact of P2Y12 inhibition by clopidogrel on cardiovascular mortality in unselected patients treated by percutaneous coronary angioplasty: a prospective registry

JACC Cardiovasc Interv. 2010 Jun;3(6):648-56. doi: 10.1016/j.jcin.2010.03.003.

Abstract

Objectives: The aim of this study was to determine whether low platelet response to the P2Y(12) receptor antagonist clopidogrel as assessed by Vasodilator-stimulated phosphoprotein flow cytometry test (VASP- FCT) predicts cardiovascular events in a high-risk population undergoing percutaneous coronary intervention (PCI).

Background: Impaired platelet responsiveness to clopidogrel is thought to be a determinant of cardiovascular events after PCI. The platelet VASP-FCT is a new assay specific to the P2Y(12) adenosine diphosphate receptor-pathway. In this test, platelet activation is expressed as platelet reactivity index (PRI).

Methods: Four-hundred sixty-one unselected patients undergoing urgent (n = 346) or planned (n = 115) PCI were prospectively enrolled. Patients were classified as low-response (LR) and response (R) to clopidogrel, depending on their PRI. Optimal PRI cutoff was determined by receiver-operator characteristic curve analysis to 61% (LR: PRI > or =61% and R: PRI <61%). Follow-up was obtained at a mean of 9 +/- 2 months in 453 patients (98.3%).

Results: At follow-up, total cardiac mortality rates and possible and total stent thrombosis were higher in LR patients. Multivariate analysis identified creatinine clearance (hazard ratio [HR]: 0.95; 95% confidence interval [CI]: 0.93 to 0.98, p < 0.001), drug-eluting stent (HR: 5.73; 95% CI: 1.40 to 23.43, p = 0.015), C-reactive protein (HR: 1.01; 95% CI: 1.001 to 1.019, p = 0.024), and LR to clopidogrel (HR: 4.00; 95% CI: 1.08 to 14.80, p = 0.037) as independent predictors of cardiac death. The deleterious impact of LR to clopidogrel on cardiovascular death was significantly higher in patients implanted with drug-eluting stent.

Conclusions: In patients undergoing PCI, LR to clopidogrel assessed by VASP-FCT is an independent predictor of cardiovascular death at the PRI cutoff value of > or =61%. The LR clinical impact seems to be dependent on the type of stent implanted.

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary / adverse effects
  • Angioplasty, Balloon, Coronary / instrumentation
  • Angioplasty, Balloon, Coronary / mortality*
  • Biomarkers / blood
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / mortality*
  • Cardiovascular Diseases / prevention & control*
  • Cell Adhesion Molecules / blood
  • Clopidogrel
  • Drug Resistance
  • Drug-Eluting Stents
  • Female
  • Flow Cytometry
  • France
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Microfilament Proteins / blood
  • Middle Aged
  • Phosphoproteins / blood
  • Phosphorylation
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Prospective Studies
  • Prosthesis Design
  • Purinergic P2 Receptor Antagonists*
  • ROC Curve
  • Receptors, Purinergic P2 / blood
  • Receptors, Purinergic P2Y12
  • Registries
  • Risk Assessment
  • Risk Factors
  • Thrombosis / blood
  • Thrombosis / mortality
  • Thrombosis / prevention & control
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Cell Adhesion Molecules
  • Microfilament Proteins
  • P2RY12 protein, human
  • Phosphoproteins
  • Platelet Aggregation Inhibitors
  • Purinergic P2 Receptor Antagonists
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2Y12
  • vasodilator-stimulated phosphoprotein
  • Clopidogrel
  • Ticlopidine