Impact of renal impairment on platelet reactivity and clinical outcomes during chronic dual antiplatelet therapy following coronary stenting

AIMS: Clinical utilization of dual antiplatelet therapy (DAPT) in patients with renal impairment (RI) following percutaneous coronary interventions (PCI) represents an urgent, unmet need choosing optimal agents, duration of treatment, and potential dose/regimen adjustment. The lack of any large randomized trials specifically in RI patients, and the absence of the uniformed clinical data reporting policy, clouds the reality. Moreover, triaging RI patients is problematic due to ongoing kidney deterioration, and the fact that RI patients are prone to both vascular occlusions and bleeding. METHODS AND RESULTS: Seven hundred and one Korean patients receiving DAPT with aspirin 100 mg/daily and clopidogrel 75 mg/daily after PCI were prospectively enrolled in the study. Patients were dichotomized into five groups according to RI: estimated glomerular filtration rate (eGFR) >90 mL/min/1.73 m(2) (RI1), 60-89 mL/min/1.73 m(2) (RI2), 30-59 mL/min/1.73 m(2) (RI3), <30 mL/min/1.73 m(2) (RI4), and undergoing dialysis (RI5). Major adverse clinical events (MACEs; cardiovascular death, myocardial infarction, stent thrombosis, and stroke) were collected for 1 year. Platelet reactivity by VerifyNow™ assay and eGFR were simultaneously assessed at 1 month after maintenance DAPT. Patients with RI exhibited a gradual significant increase of residual platelet reactivity during DAPT, dependent on eGFR deterioration [191 ± 72 PRU (RI1) vs. 216 ± 78 PRU (RI2) vs. 248 ± 80 PRU (RI3) vs. 264 ± 70 PRU (RI4) vs. 317 ± 96 PRU (RI5), P < 0.001] being the highest in the dialyses group. Declined eGFR has been gradually associated with advancing age (OR = 1.03, 95% CI = 1.00-1.05; P = 0.032), female gender (OR = 1.7, 95% CI = 1.1-2.5; P = 0.01), diminished smoking rates (OR = 0.6, 95% CI = 0.37-1.00; P = 0.05), hypertension (OR = 1.8, 95% CI = 1.3-2.5; P < 0.001); diabetes (OR = 1.5, 95% CI = 1.1-2.1; P = 0.007), and MACE (HR = 13.9; 95% CI = 1.6-124.3; P = 0.02 for RI4; and HR = 31.9; 95% CI = 2.9-351.9; P = 0.005 for dialysis), but not for bleeding (P = 0.143). Major adverse clinical event risks still remained significant for RI4 (P = 0.027) and RI5 (P = 0.002) by multivariate Cox hazard regression estimates. CONCLUSION: Renal impairment is associated with gradual elevation of residual platelet reactivity while on DAPT, enhancing MACE risks, but not bleeding events. These data should be confirmed in a large randomized outcome-driven trial, and may justify future maintenance-phase DAPT regimen/dose adjustment in RI patients.