title: Platelet Reactivity and Clinical Outcomes After Coronary Artery Implantation of Drug-Eluting Stents in Subjects With Peripheral Arterial Disease: Analysis From the ADAPT-DES Study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents).
abstract: BACKGROUND
  Patients with peripheral arterial disease (PAD) have high rates of adverse cardiovascular events after percutaneous coronary intervention and may additionally have heightened platelet reactivity. This study assessed the relationship between platelet reactivity and clinical outcomes after percutaneous coronary interventions among subjects with and without PAD.
  
  
  RESULTS
  ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective, multicenter registry of patients treated with coronary drug-eluting stents. Platelet reactivity was assessed by the VerifyNow point-of-care assay; high on-treatment platelet reactivity (HPR) was defined as P2Y12 reaction units >208. A propensity-adjusted multivariable analysis was performed to determine the relationship between PAD, platelet reactivity, and subsequent adverse events (definite or probable stent thrombosis, all-cause mortality, myocardial infarction, and clinically relevant bleeding). Among 8582 patients, 10.2% had a history of PAD. Patients with PAD were older and more likely to have comorbid conditions; however, mean P2Y12 reaction units and HPR were not significantly different between PAD and no PAD groups. Patients with PAD had higher 2-year rates of all-cause mortality, myocardial infarction, stent thrombosis, and clinically relevant bleeding. Associations between HPR and adverse events were similar in PAD and no PAD groups, without evidence of interaction; however, adverse event rates were highest among subjects with both PAD and HPR. In a propensity-adjusted multivariable model, both PAD and HPR were independent predictors of myocardial infarction at 2 years.
  
  
  CONCLUSIONS
  A history of PAD was associated with ischemic and bleeding outcomes 2 years after successful coronary drug-eluting stent implantation; however, these associations did not seem to be directly mediated by heightened platelet reactivity.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.
authors.affiliation: From the University of Toledo Medical Center, OH (R.G.); Cardiovascular Research Foundation, New York, NY (A.J.K., M.O.O., G.W., R.M., O.B.-Y., G.W.S.); NewYork-Presbyterian Hospital/Columbia University Medical Center, NY (A.J.K., G.W., O.B.-Y., G.W.S.); Helios Amper-Klinikum, Dachau, Germany (B.W.); Sanger Heart & Vascular Institute/Carolinas HealthCare System, Charlotte, NC (M.J.R.); Wellmont CVA Heart Institute, Kingsport, TN (D.C.M.); Shaare Zedek Medical Center, Jerusalem, Israel (G.W.); LeBauer-Brodie Center for Cardiovascular Research and Education/Cone Health, Greensboro, NC (T.D.S., B.R.B.); and Icahn School of Medicine at Mount Sinai, New York, NY (R.M.).
authors.forename: Rajesh
authors.initials: R
authors.lastname: Gupta
authors.affiliation: From the University of Toledo Medical Center, OH (R.G.); Cardiovascular Research Foundation, New York, NY (A.J.K., M.O.O., G.W., R.M., O.B.-Y., G.W.S.); NewYork-Presbyterian Hospital/Columbia University Medical Center, NY (A.J.K., G.W., O.B.-Y., G.W.S.); Helios Amper-Klinikum, Dachau, Germany (B.W.); Sanger Heart & Vascular Institute/Carolinas HealthCare System, Charlotte, NC (M.J.R.); Wellmont CVA Heart Institute, Kingsport, TN (D.C.M.); Shaare Zedek Medical Center, Jerusalem, Israel (G.W.); LeBauer-Brodie Center for Cardiovascular Research and Education/Cone Health, Greensboro, NC (T.D.S., B.R.B.); and Icahn School of Medicine at Mount Sinai, New York, NY (R.M.). akirtane@columbia.edu.
authors.forename: Ajay J
authors.initials: AJ
authors.lastname: Kirtane
authors.affiliation: From the University of Toledo Medical Center, OH (R.G.); Cardiovascular Research Foundation, New York, NY (A.J.K., M.O.O., G.W., R.M., O.B.-Y., G.W.S.); NewYork-Presbyterian Hospital/Columbia University Medical Center, NY (A.J.K., G.W., O.B.-Y., G.W.S.); Helios Amper-Klinikum, Dachau, Germany (B.W.); Sanger Heart & Vascular Institute/Carolinas HealthCare System, Charlotte, NC (M.J.R.); Wellmont CVA Heart Institute, Kingsport, TN (D.C.M.); Shaare Zedek Medical Center, Jerusalem, Israel (G.W.); LeBauer-Brodie Center for Cardiovascular Research and Education/Cone Health, Greensboro, NC (T.D.S., B.R.B.); and Icahn School of Medicine at Mount Sinai, New York, NY (R.M.).
authors.forename: M Ozgu
authors.initials: MO
authors.lastname: Ozan
authors.affiliation: From the University of Toledo Medical Center, OH (R.G.); Cardiovascular Research Foundation, New York, NY (A.J.K., M.O.O., G.W., R.M., O.B.-Y., G.W.S.); NewYork-Presbyterian Hospital/Columbia University Medical Center, NY (A.J.K., G.W., O.B.-Y., G.W.S.); Helios Amper-Klinikum, Dachau, Germany (B.W.); Sanger Heart & Vascular Institute/Carolinas HealthCare System, Charlotte, NC (M.J.R.); Wellmont CVA Heart Institute, Kingsport, TN (D.C.M.); Shaare Zedek Medical Center, Jerusalem, Israel (G.W.); LeBauer-Brodie Center for Cardiovascular Research and Education/Cone Health, Greensboro, NC (T.D.S., B.R.B.); and Icahn School of Medicine at Mount Sinai, New York, NY (R.M.).
authors.forename: Bernhard
authors.initials: B
authors.lastname: Witzenbichler
authors.affiliation: From the University of Toledo Medical Center, OH (R.G.); Cardiovascular Research Foundation, New York, NY (A.J.K., M.O.O., G.W., R.M., O.B.-Y., G.W.S.); NewYork-Presbyterian Hospital/Columbia University Medical Center, NY (A.J.K., G.W., O.B.-Y., G.W.S.); Helios Amper-Klinikum, Dachau, Germany (B.W.); Sanger Heart & Vascular Institute/Carolinas HealthCare System, Charlotte, NC (M.J.R.); Wellmont CVA Heart Institute, Kingsport, TN (D.C.M.); Shaare Zedek Medical Center, Jerusalem, Israel (G.W.); LeBauer-Brodie Center for Cardiovascular Research and Education/Cone Health, Greensboro, NC (T.D.S., B.R.B.); and Icahn School of Medicine at Mount Sinai, New York, NY (R.M.).
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rinaldi
authors.affiliation: From the University of Toledo Medical Center, OH (R.G.); Cardiovascular Research Foundation, New York, NY (A.J.K., M.O.O., G.W., R.M., O.B.-Y., G.W.S.); NewYork-Presbyterian Hospital/Columbia University Medical Center, NY (A.J.K., G.W., O.B.-Y., G.W.S.); Helios Amper-Klinikum, Dachau, Germany (B.W.); Sanger Heart & Vascular Institute/Carolinas HealthCare System, Charlotte, NC (M.J.R.); Wellmont CVA Heart Institute, Kingsport, TN (D.C.M.); Shaare Zedek Medical Center, Jerusalem, Israel (G.W.); LeBauer-Brodie Center for Cardiovascular Research and Education/Cone Health, Greensboro, NC (T.D.S., B.R.B.); and Icahn School of Medicine at Mount Sinai, New York, NY (R.M.).
authors.forename: D Christopher
authors.initials: DC
authors.lastname: Metzger
authors.affiliation: From the University of Toledo Medical Center, OH (R.G.); Cardiovascular Research Foundation, New York, NY (A.J.K., M.O.O., G.W., R.M., O.B.-Y., G.W.S.); NewYork-Presbyterian Hospital/Columbia University Medical Center, NY (A.J.K., G.W., O.B.-Y., G.W.S.); Helios Amper-Klinikum, Dachau, Germany (B.W.); Sanger Heart & Vascular Institute/Carolinas HealthCare System, Charlotte, NC (M.J.R.); Wellmont CVA Heart Institute, Kingsport, TN (D.C.M.); Shaare Zedek Medical Center, Jerusalem, Israel (G.W.); LeBauer-Brodie Center for Cardiovascular Research and Education/Cone Health, Greensboro, NC (T.D.S., B.R.B.); and Icahn School of Medicine at Mount Sinai, New York, NY (R.M.).
authors.forename: Giora
authors.initials: G
authors.lastname: Weisz
authors.affiliation: From the University of Toledo Medical Center, OH (R.G.); Cardiovascular Research Foundation, New York, NY (A.J.K., M.O.O., G.W., R.M., O.B.-Y., G.W.S.); NewYork-Presbyterian Hospital/Columbia University Medical Center, NY (A.J.K., G.W., O.B.-Y., G.W.S.); Helios Amper-Klinikum, Dachau, Germany (B.W.); Sanger Heart & Vascular Institute/Carolinas HealthCare System, Charlotte, NC (M.J.R.); Wellmont CVA Heart Institute, Kingsport, TN (D.C.M.); Shaare Zedek Medical Center, Jerusalem, Israel (G.W.); LeBauer-Brodie Center for Cardiovascular Research and Education/Cone Health, Greensboro, NC (T.D.S., B.R.B.); and Icahn School of Medicine at Mount Sinai, New York, NY (R.M.).
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Stuckey
authors.affiliation: From the University of Toledo Medical Center, OH (R.G.); Cardiovascular Research Foundation, New York, NY (A.J.K., M.O.O., G.W., R.M., O.B.-Y., G.W.S.); NewYork-Presbyterian Hospital/Columbia University Medical Center, NY (A.J.K., G.W., O.B.-Y., G.W.S.); Helios Amper-Klinikum, Dachau, Germany (B.W.); Sanger Heart & Vascular Institute/Carolinas HealthCare System, Charlotte, NC (M.J.R.); Wellmont CVA Heart Institute, Kingsport, TN (D.C.M.); Shaare Zedek Medical Center, Jerusalem, Israel (G.W.); LeBauer-Brodie Center for Cardiovascular Research and Education/Cone Health, Greensboro, NC (T.D.S., B.R.B.); and Icahn School of Medicine at Mount Sinai, New York, NY (R.M.).
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Brodie
authors.affiliation: From the University of Toledo Medical Center, OH (R.G.); Cardiovascular Research Foundation, New York, NY (A.J.K., M.O.O., G.W., R.M., O.B.-Y., G.W.S.); NewYork-Presbyterian Hospital/Columbia University Medical Center, NY (A.J.K., G.W., O.B.-Y., G.W.S.); Helios Amper-Klinikum, Dachau, Germany (B.W.); Sanger Heart & Vascular Institute/Carolinas HealthCare System, Charlotte, NC (M.J.R.); Wellmont CVA Heart Institute, Kingsport, TN (D.C.M.); Shaare Zedek Medical Center, Jerusalem, Israel (G.W.); LeBauer-Brodie Center for Cardiovascular Research and Education/Cone Health, Greensboro, NC (T.D.S., B.R.B.); and Icahn School of Medicine at Mount Sinai, New York, NY (R.M.).
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.affiliation: From the University of Toledo Medical Center, OH (R.G.); Cardiovascular Research Foundation, New York, NY (A.J.K., M.O.O., G.W., R.M., O.B.-Y., G.W.S.); NewYork-Presbyterian Hospital/Columbia University Medical Center, NY (A.J.K., G.W., O.B.-Y., G.W.S.); Helios Amper-Klinikum, Dachau, Germany (B.W.); Sanger Heart & Vascular Institute/Carolinas HealthCare System, Charlotte, NC (M.J.R.); Wellmont CVA Heart Institute, Kingsport, TN (D.C.M.); Shaare Zedek Medical Center, Jerusalem, Israel (G.W.); LeBauer-Brodie Center for Cardiovascular Research and Education/Cone Health, Greensboro, NC (T.D.S., B.R.B.); and Icahn School of Medicine at Mount Sinai, New York, NY (R.M.).
authors.forename: Ori
authors.initials: O
authors.lastname: Ben-Yehuda
authors.affiliation: From the University of Toledo Medical Center, OH (R.G.); Cardiovascular Research Foundation, New York, NY (A.J.K., M.O.O., G.W., R.M., O.B.-Y., G.W.S.); NewYork-Presbyterian Hospital/Columbia University Medical Center, NY (A.J.K., G.W., O.B.-Y., G.W.S.); Helios Amper-Klinikum, Dachau, Germany (B.W.); Sanger Heart & Vascular Institute/Carolinas HealthCare System, Charlotte, NC (M.J.R.); Wellmont CVA Heart Institute, Kingsport, TN (D.C.M.); Shaare Zedek Medical Center, Jerusalem, Israel (G.W.); LeBauer-Brodie Center for Cardiovascular Research and Education/Cone Health, Greensboro, NC (T.D.S., B.R.B.); and Icahn School of Medicine at Mount Sinai, New York, NY (R.M.).
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
mesh_terms: D000368:Aged; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D003328:Coronary Thrombosis / Q000097:blood / Q000209:etiology; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000295:instrumentation* / Q000401:mortality; D058729:Peripheral Arterial Disease / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000401:mortality; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011237:Predictive Value of Tests; D057216:Propensity Score; D016016:Proportional Hazards Models; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D012042:Registries; D012307:Risk Factors; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: coronary artery disease; percutaneous coronary intervention; peripheral arterial disease; stent; thrombosis