Author + information
- 1Department of Cardiology, Dong-A University Hospital, Busan, South Korea
- 2Clinical Trial Center, Dong-A University Hospital, Busan, South Korea
- 3Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
- 4HeartDrug Research Laboratories, Johns Hopkins University, Baltimore, MD
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. Lack of any large randomized trials specifically in RI patients, and 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.
701 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 5 groups according to RI: estimated glomerular filtration rate (eGFR)> 90 mL/min/1.73m2 (RI1), 60 - 89 mL/min/1.73m2 (RI2), 30 - 59 mL/min/1.73m2 (RI3), < 30 mL/min/1.73m2 (RI4), and undergoing dialysis (RI5). Major adverse clinical event (MACE) (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 gradual significant increase of residual platelet reactivity during DAPT, dependent on eGFR deterioration [191± 72PRU (RI1) vs. 216± 78PRU (RI2) vs. 248± 80PRU (RI3) vs. 264±70PRU (RI4) vs. 317± 96PRU (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; CI=1.6-124.3;p=0.02 for RI4; and (HR=31.9; CI=2.9-351.9;p=0.005 for dialysis), but not for bleeding (p=0.143). MACE risks still remained significant for RI4 (p=0.027), and RI5 (0.002) by multivariate Cox hazard regression estimates.
RI is strongly associated with gradual elevation of residual platelet reactivity while on DAPT, enhanced 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.