To determine whether low platelet response to the P2Y₁₂ receptor antagonist clopidogrel as assessed by VAsodilator Stimulated Phosphoprotein flow cytometry test (VASP-FCT) has the same deleterious clinical impact in patients with or without chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI).

Whilst both CKD and impaired platelet responsiveness to clopidogrel are strong predictors of unfavourable outcome after PCI, the deleterious impact of their association is unknown. The platelet VASP-FCT assay is specific of the P2Y₁₂ ADP receptor-pathway. In this test, platelet activation is expressed as Platelet Reactivity Index (PRI).

440 unselected patients (CKD: 126 (eGFR<60ml/min/1.73m²), NoCKD: 314 eGFR>60ml/min/1.73m²) undergoing urgent (n = 336) or planned (n = 104) PCI were prospectively enrolled. In each sub-group, patients were classified as low-responders (LR: PRI≥61%) and responders (R: PRI<61%) to clopidogrel. The 61% threshold was previously defined as the optimal cut-off value to predict cardiac death following PCI.

At a mean follow-up of 9 ± 2 months, cardiac death, probable and possible stent thrombosis rates were higher in CKD patients. In this sub-group, cardiac death, total stent thrombosis and MACE were dramatically increased in LR patients, especially when treated with drug eluting stent (DES). Conversely, in NoCKD patients, LR was not associated with poorer cardiovascular outcome. Multivariate analysis identified Killip class ≥3, DES implantation and the interaction between LR and CKD (HR 11.96 [1.22–116.82]; p = 0.033) as independent predictors of cardiac death.

In CKD patients, cardiovascular mortality following PCI is mainly related to impaired P2Y₁₂ inhibition.