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

ABSTRACT

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.