title: Dual antiplatelet therapy is associated with prolonged survival after lower extremity revascularization.
abstract: BACKGROUND
  Dual antiplatelet therapy (DAPT) after coronary stenting prolongs survival by preventing both in-stent thrombosis and other cardiovascular atherothrombotic events. Patients with peripheral artery disease (PAD) typically have a heavy burden of unrevascularized coronary artery disease and also stand to benefit from increased atherothrombotic protection with DAPT. The potential benefit of DAPT compared with aspirin alone in patients with PAD is not well described.
  
  
  METHODS
  We identified all patients undergoing an initial elective lower extremity revascularization (bypass or endovascular) from 2003 to 2016 in the Vascular Quality Initiative registry discharged on aspirin or aspirin plus a thienopyridine antiplatelet agent (DAPT). We first estimated models predicting the likelihood of receiving DAPT and then used inverse probability weighting to account for baseline differences in the likelihood of receiving DAPT and compared late survival. For sensitivity analysis, we also performed Cox proportion hazard modeling on the unweighted cohorts and generated adjusted survival curves.
  
  
  RESULTS
  We identified 57,041 patients undergoing lower extremity revascularization (28% bypass). Of 15,985 bypasses (69% for critical limb ischemia [CLI]), 38% were discharged on DAPT. Of 41,056 endovascular interventions (39% for CLI), 69% were discharged on DAPT. Analyses using inverse probability weighting demonstrated a small survival benefit to DAPT at 1 year for bypass (93% vs 92% [P = .001]) and endovascular interventions (93% vs 92% [P = .005]) that was sustained through 5 years of follow-up (bypass, 80% vs 78% [P = .004]; endovascular, 76% vs 73% [P = .002]). When stratified by severity of PAD, DAPT had a survival benefit for patients with CLI undergoing bypass (5 years, 70% vs 66% [P = .04]) and endovascular intervention (5 years, 71% vs 67% [P = .01]) but not for patients with claudication (bypass, 89% vs 88% [P = .36]; endovascular, 87% vs 85% [P = .46]). The protective effect of DAPT was similar when using Cox proportional hazard models after bypass (hazard ratio, 0.81 [95% confidence interval, 0.72-0.90]) and endovascular intervention (hazard ratio, 0.89 [95% confidence interval, 0.83-0.95]).
  
  
  CONCLUSIONS
  DAPT at time of discharge was associated with prolonged survival for patients with CLI undergoing lower extremity revascularization but not for those with claudication. Further research is needed to quantify the risks associated with DAPT and to identify subgroups at increased risk of thrombotic and bleeding complications to guide medical management of patients with PAD.
authors: Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass.
authors: Peter A
authors: PA
authors: Soden
authors: Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass.
authors: Sara L
authors: SL
authors: Zettervall
authors: Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass.
authors: Klaas H J
authors: KH
authors: Ultee
authors: Division of General Medicine and Primary Care, Department of Health Care Policy, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass.
authors: Bruce E
authors: BE
authors: Landon
authors: Department of Biomedical Data Science and the Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine at Dartmouth, Lebanon, NH.
authors: A James
authors: AJ
authors: O'Malley
authors: Section of Vascular Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH.
authors: Philip P
authors: PP
authors: Goodney
authors: Division of Vascular and Endovascular Surgery, Mayo Clinic, Rochester, Minn.
authors: Randall R
authors: RR
authors: DeMartino
authors: Division of Vascular Surgery, Emory University School of Medicine, Atlanta, and Atlanta VA Medical Center, Decatur, Ga.
authors: Shipra
authors: S
authors: Arya
authors: Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass. Electronic address: mscherm@bidmc.harvard.edu.
authors: Marc L
authors: ML
authors: Schermerhorn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D016638:Critical Illness; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007383:Intermittent Claudication / Q000000981:diagnostic imaging / Q000401:mortality / Q000601:surgery*; D007511:Ischemia / Q000000981:diagnostic imaging / Q000401:mortality / Q000601:surgery*; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000000981:diagnostic imaging / Q000401:mortality / Q000601:surgery*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D058924:Thienopyridines / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014656:Vascular Surgical Procedures / Q000009:adverse effects / Q000401:mortality*
chemical_list: D010975:Platelet Aggregation Inhibitors; D058924:Thienopyridines; D001241:Aspirin