Cardiovascular mortality in chronic kidney disease patients undergoing percutaneous coronary intervention is mainly related to impaired P2Y12 inhibition by clopidogrel.
OBJECTIVE
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.
Pôle d'activité médico-chirurgicale Cardiovasculaire, Nouvel Hôpital Civil, Université de Strasbourg, Strasbourg, France. olivier.morel@chru-strasbourg.fr
Olivier
O
Morel
Soraya
S
El Ghannudi
Laurence
L
Jesel
Bogdan
B
Radulescu
Nicolas
N
Meyer
Marie-Louise
ML
Wiesel
Sophie
S
Caillard
Umberto
U
Campia
Bruno
B
Moulin
Christian
C
Gachet
Patrick
P
Ohlmann
D054058:Acute Coronary Syndrome / Q000150:complications / Q000401:mortality* / Q000628:therapy; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000401:mortality*; D001792:Blood Platelets / Q000187:drug effects; D002423:Cause of Death; D000077144:Clopidogrel; D015331:Cohort Studies; D023921:Coronary Stenosis / Q000150:complications / Q000401:mortality* / Q000628:therapy; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D053208:Kaplan-Meier Estimate; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D012016:Reference Values; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000175:diagnosis; D018570:Risk Assessment; D016019:Survival Analysis; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D013988:Ticlopidine