title: Variability and persistence of aspirin response in lower extremity peripheral arterial disease patients.
abstract: OBJECTIVE
  To determine the prevalence of poor response to aspirin (ASA) therapy over 12-month follow-up in patients with lower extremity peripheral arterial disease (PAD), and to compare the classification agreement among different ASA response assays.
  
  
  METHODS
  Patients with PAD on ASA therapy at baseline were included from the ongoing Effect of Lipid Modification on Peripheral Arterial Disease after Endovascular Intervention Trial (ELIMIT), which is a randomized trial testing whether combination treatment with ezetimibe, niacin, and a statin will halt/regress atherosclerosis compared with statin monotherapy. Patients who had baseline platelet testing and repeat testing at 6-month or 12-month follow-up were included. ASA responsiveness was tested using three different assays: Optical aggregation with 0.5 mg/mL of arachidonic acid (AA), optical aggregation with 10 μM of adenosine diphosphate (ADP), and platelet function analyzer-100 (PFA-100) testing with collagen/epinephrine (Epi) loaded cartridges. ASA response was defined as AA aggregation <30%, ADP aggregation <70%, or PFA-100 Epi >164 seconds. Patients who showed response to ASA at baseline were classified as Responders. Poor response to ASA was defined as AA aggregation ≥ 30%, ADP aggregation ≥ 70%, or PFA-100 Epi ≤ 164 seconds. Patients who showed poor response (PR) to an assay at baseline, but then were responsive at follow-up visits were classified as Initial PRs. Patients who showed poor response at baseline and all follow-up visits were classified as Persistent PRs. The classification agreement between assays was tested using the kappa statistic.
  
  
  RESULTS
  Of 102 patients randomized in ELIMIT, 80 patients satisfied inclusion criteria. There were no significant baseline demographic differences between Responders, Initial PRs, and Persistent PRs. The prevalence of persistent poor response varied by the assay used; 5% of subjects (4/80) were Persistent PRs by AA aggregation, compared with 27.5% (22/80) of subjects by ADP aggregation and 9.9% (7/71) of patients by PFA-100 Epi. Regarding the agreement of the assays, only AA aggregation and PFA-100 Epi agreed significantly (K = 0.3223; 95% confidence interval [CI] 0.15-0.493; P = .0001), and though statistically significant, the magnitude of this agreement is small. AA aggregation and ADP aggregation did not agree (K = 0.1161; 95% CI -0.004-0.236; P = .029), nor did ADP aggregation and PFA-100 Epi (K = 0.0044; 95% CI -0.151-0.160; P = .48).
  
  
  CONCLUSIONS
  Between 5% and 27.5% of PAD patients were Persistent PRs to ASA over 6- to 12-month follow-up using different platelet assays. Further, these commonly used platelet assays show weak agreement in determining poor response to aspirin.
authors.affiliation: Section of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, Tex, USA. jsaunde@med.umich.edu
authors.forename: Justin
authors.initials: J
authors.lastname: Saunders
authors.forename: Vijay
authors.initials: V
authors.lastname: Nambi
authors.forename: Kay T
authors.initials: KT
authors.lastname: Kimball
authors.forename: Salim S
authors.initials: SS
authors.lastname: Virani
authors.forename: Joel D
authors.initials: JD
authors.lastname: Morrisett
authors.forename: Alan B
authors.initials: AB
authors.lastname: Lumsden
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.forename: Jing-Fei
authors.initials: JF
authors.lastname: Dong
mesh_terms: D000244:Adenosine Diphosphate; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000800:Angioplasty, Balloon / Q000295:instrumentation; D016718:Arachidonic Acid; D001241:Aspirin / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use; D004311:Double-Blind Method; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000627:therapeutic use; D058729:Peripheral Arterial Disease / Q000097:blood / Q000188:drug therapy*; D015990:Placebo Effect; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011237:Predictive Value of Tests; D015607:Stents; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001384:Azetidines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D010975:Platelet Aggregation Inhibitors; D009525:Niacin; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D000069438:Ezetimibe; D001241:Aspirin