Cardiovascular Mortality in Chronic Kidney Disease Patients Undergoing Percutaneous Coronary Intervention Is Mainly Related to Impaired P2Y12 Inhibition by Clopidogrel

Study Questions:

What is the effect of low platelet response to the P2Y12 receptor antagonist clopidogrel on outcomes in patients with or without chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI)?

Methods:

A total of 440 unselected patients (CKD: 126, estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2; no-CKD: 314, eGFR >60 ml/min/1.73 m2) undergoing urgent (n = 336) or planned (n = 104) PCI were prospectively enrolled. In each subgroup, patients were classified as low-responders (LR: platelet reactivity index [PRI] ≥61%) or responders (R: PRI <61%) to clopidogrel. The primary endpoints of the study were all-cause mortality, cardiovascular mortality, ST-segment elevation myocardial infarction, and non–ST-segment elevation myocardial infarction. Multivariate analysis of survival rates was done using Cox models.

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 major adverse cardiac events (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, 1.22-116.82; p = 0.033) as independent predictors of cardiac death.

Conclusions:

The authors concluded that in CKD patients, the presence of low platelet response to clopidogrel is associated with worse outcomes after PCI.

Perspective:

The primary finding of this study is that the presence of low platelet response to clopidogrel is associated with increased all-cause mortality, cardiac death, stent thrombosis, and MACE after PCI in patients with CKD. However, in patients with preserved eGFR, these outcomes do not appear to differ between those with normal and those with reduced platelet response to clopidogrel. Furthermore, these data confirm the association between the presence of CKD and worse all-cause mortality and cardiovascular outcomes. It is possible that the evaluation of responsiveness to clopidogrel and use of alternative agents may be useful for the management of CKD patients treated by PCI, but needs further prospective evaluation.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention

Keywords: Myocardial Infarction, Follow-Up Studies, Thrombosis, Drug-Eluting Stents, Survival Rate, Glomerular Filtration Rate, Ticlopidine, Blood Platelets, Renal Insufficiency, Chronic, Stents, Percutaneous Coronary Intervention


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