title: Impact of renal impairment on platelet reactivity and clinical outcomes during chronic dual antiplatelet therapy following coronary stenting.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Cardiology, Dong-A University Hospital, Busan, South Korea Clinical Trial Center, Dong-A University Hospital, Busan, South Korea Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Long Zhe
authors.initials: LZ
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Dong-A University Hospital, Busan, South Korea Clinical Trial Center, Dong-A University Hospital, Busan, South Korea kimmh@dau.ac.kr.
authors.forename: Moo Hyun
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Clinical Trial Center, Dong-A University Hospital, Busan, South Korea.
authors.forename: Chang Heon
authors.initials: CH
authors.lastname: Shim
authors.affiliation: Clinical Trial Center, Dong-A University Hospital, Busan, South Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: HeartDrug Research Laboratories™, Johns Hopkins University, Osler Medical Building, 7600 Osler Drive, Suite 307, Baltimore, MD 21204, USA.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Serebruany
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000187:drug effects*; D003327:Coronary Disease / Q000601:surgery*; D003328:Coronary Thrombosis / Q000517:prevention & control; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000097:blood* / Q000150:complications*; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000517:prevention & control; D011446:Prospective Studies; D015607:Stents
chemical_list: D010975:Platelet Aggregation Inhibitors
keywords: Antiplatelet therapy; Clinical outcomes; Glomerular filtration; Renal function