title: Comparison of Three Tests to Distinguish Platelet Reactivity in Patients with Renal Impairment during Dual Antiplatelet Therapy.
abstract: BACKGROUND
  Clopidogrel and aspirin combination remains a cornerstone for modern dual antiplatelet therapy (DAPT) following coronary stenting. Although monitoring is not currently recommended, certain high-risk cohorts may benefit from tailoring antiplatelet options to reduce thrombotic or/and hemorrhagic risks. Patients with diminished estimated glomerular filtration rate (eGFR) are prone to both vascular occlusions and bleeding events in whom monitoring may be especially advantageous. We compared the residual platelet reactivity assessed by 3 conventional tests during the maintenance antiplatelet therapy dependent on eGFR.
  
  
  METHODS
  Post-stenting patients (n = 701) receiving aspirin 100 mg/daily and clopidogrel 75 mg/daily were prospectively enrolled in the cross-sectional single-center study. Patients were dichotomized into 5 groups: eGFR >90, 60-89, 30-59, <30 ml/min/1.73 m2, and dialysis. Platelet reactivity by VerifyNow™, light transmittance aggregometry (LTA), and Multiplate analyzer by multiple electrode platelet aggregometry (MEA) assays together with eGFR calculations were done simultaneously at 1 month after coronary stenting.
  
  
  RESULTS
  VerifyNow assay distinguished residual platelet reactivity dependent on eGFR deterioration (191 ± 72 vs. 216 ± 78 vs. 248 ± 80 vs. 264 ± 70 vs. 317 ± 96 PRU; p < 0.001). In contrast, LTA (34.3 ± 18.1 vs. 34.7 ± 18.1 vs. 38.0 ± 16.6 vs. 33.0 ± 17.3 vs. 34.1 ± 29.3%; p = 0.242), or MEA (37.2 ± 19.6 vs. 33.8 ± 18.4 vs. 38.6 ± 21.4 vs. 36.5 ± 20.5 vs. 38.3 ± 28.3 AU/min; p = 0.086) failed to triage platelet reactivity in renal patients. Agreement among assays to identify patients with impaired platelet reactivity and eGFR during antiplatelet therapy was low. The multivariable regression analyses confirmed the VerifyNow advantage, since the differences in the platelet reactivity were highly significant for all renal impairment (RI) groups. In contrast, LTA did not distinguish RI patients, and for the MEA, only RI5 (dialysis) cohort exhibit borderline significant decline of residual platelet reactivity.
  
  
  CONCLUSIONS
  Among 3 assays, VerifyNow was capable to reliably triage residual platelet reactivity in post-stenting DAPT patients dependent on the gradual decline of eGFR during therapy with clopidogrel and aspirin. These data should be confirmed in a large validation longitudinal trial, and may justify future platelet activity monitoring for potential regimen/dose adjustment in high-risk patients. The clinical implications of these data are still unclear, but may give an indication as to whether or when DAPT dose adjustment will become a reality.
authors.affiliation: Department of Cardiology, Dong-A University Hospital, Busan, South Korea.
authors.forename: Long Zhe
authors.initials: LZ
authors.lastname: Guo
authors.forename: Moo Hyun
authors.initials: MH
authors.lastname: Kim
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Kim
authors.forename: Jong Seong
authors.initials: JS
authors.lastname: Park
authors.forename: Enze
authors.initials: E
authors.lastname: Jin
authors.forename: Chang Heon
authors.initials: CH
authors.lastname: Shim
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Victor L
authors.initials: VL
authors.lastname: Serebruany
mesh_terms: D000368:Aged; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use; D000077144:Clopidogrel; D003430:Cross-Sectional Studies; D005260:Female; D005919:Glomerular Filtration Rate; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011446:Prospective Studies; D013927:Thrombosis / Q000517:prevention & control; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin