title: Polymer-free Drug-Coated Coronary Stents in Patients at High Bleeding Risk.
abstract: BACKGROUND
  Patients at high risk for bleeding who undergo percutaneous coronary intervention (PCI) often receive bare-metal stents followed by 1 month of dual antiplatelet therapy. We studied a polymer-free and carrier-free drug-coated stent that transfers umirolimus (also known as biolimus A9), a highly lipophilic sirolimus analogue, into the vessel wall over a period of 1 month.
  
  
  METHODS
  In a randomized, double-blind trial, we compared the drug-coated stent with a very similar bare-metal stent in patients with a high risk of bleeding who underwent PCI. All patients received 1 month of dual antiplatelet therapy. The primary safety end point, tested for both noninferiority and superiority, was a composite of cardiac death, myocardial infarction, or stent thrombosis. The primary efficacy end point was clinically driven target-lesion revascularization.
  
  
  RESULTS
  We enrolled 2466 patients. At 390 days, the primary safety end point had occurred in 112 patients (9.4%) in the drug-coated-stent group and in 154 patients (12.9%) in the bare-metal-stent group (risk difference, -3.6 percentage points; 95% confidence interval [CI], -6.1 to -1.0; hazard ratio, 0.71; 95% CI, 0.56 to 0.91; P<0.001 for noninferiority and P=0.005 for superiority). During the same time period, clinically driven target-lesion revascularization was needed in 59 patients (5.1%) in the drug-coated-stent group and in 113 patients (9.8%) in the bare-metal-stent group (risk difference, -4.8 percentage points; 95% CI, -6.9 to -2.6; hazard ratio, 0.50; 95% CI, 0.37 to 0.69; P<0.001).
  
  
  CONCLUSIONS
  Among patients at high risk for bleeding who underwent PCI, a polymer-free umirolimus-coated stent was superior to a bare-metal stent with respect to the primary safety and efficacy end points when used with a 1-month course of dual antiplatelet therapy. (Funded by Biosensors Europe; LEADERS FREE ClinicalTrials.gov number, NCT01623180.).
authors.affiliation: From Hôpital de la Tour, Geneva (P.U.), Triemli Hospital, Zurich (F.E.), and Biosensors Europe, Morges (S.G., H.-P.S.) - all in Switzerland; MonashHeart and Monash University, Melbourne, VIC, Australia (I.T.M.); Instituto Dante Pazzanese de Cardiologia, São Paulo (A.A.); London School of Hygiene and Tropical Medicine, London (S.J.P., J.G.), the Dorset Heart Centre Royal Bournemouth Hospital, Bournemouth (S.T.), and West of Scotland Regional Heart and Lung Centre Golden Jubilee National Hospital, Glasgow (K.O.) - all in the United Kingdom; Toulouse Rangueil Hospital, Toulouse (D.C.), Pôle Santé République, Clermont-Ferrand (J.L.), Clinique de la Fontaine, Dijon (P.B.), Hôpital Claude Galien, Institut Cardiovasculaire Paris Sud (ICPS), Générale de Santé, Quincy-sous-Sénart (P.G.), Clinique Saint Hilaire, Rouen (J.B.), Groupe Hospitalier Mutualiste de Grenoble, Grenoble (M.A.), and ICPS, Générale de Santé, Massy (M.-C.M.) - all in France; Contilia Heart and Vascular Center, Elisabeth Krankenhaus, Essen (C.N.), and Herzzentrum Segeberger Kliniken, Bad Segeberg (G.R.) - both in Germany; Complejo Hospital Meixoeiro, Vigo, (A.I.), and Arrixaca University Hospital, Murcia (M.V.-C.) - both in Spain; and the Institute Jantung Negara, Kuala Lumpur, Malaysia (R.Z.).
authors.forename: Philip
authors.initials: P
authors.lastname: Urban
authors.forename: Ian T
authors.initials: IT
authors.lastname: Meredith
authors.forename: Alexandre
authors.initials: A
authors.lastname: Abizaid
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Pocock
authors.forename: Didier
authors.initials: D
authors.lastname: Carrié
authors.forename: Christoph
authors.initials: C
authors.lastname: Naber
authors.forename: Janusz
authors.initials: J
authors.lastname: Lipiecki
authors.forename: Gert
authors.initials: G
authors.lastname: Richardt
authors.forename: Andres
authors.initials: A
authors.lastname: Iñiguez
authors.forename: Philippe
authors.initials: P
authors.lastname: Brunel
authors.forename: Mariano
authors.initials: M
authors.lastname: Valdes-Chavarri
authors.forename: Philippe
authors.initials: P
authors.lastname: Garot
authors.forename: Suneel
authors.initials: S
authors.lastname: Talwar
authors.forename: Jacques
authors.initials: J
authors.lastname: Berland
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdellaoui
authors.forename: Franz
authors.initials: F
authors.lastname: Eberli
authors.forename: Keith
authors.initials: K
authors.lastname: Oldroyd
authors.forename: Robaayah
authors.initials: R
authors.lastname: Zambahari
authors.forename: John
authors.initials: J
authors.lastname: Gregson
authors.forename: Samantha
authors.initials: S
authors.lastname: Greene
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Stoll
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Morice
mesh_terms: D000368:Aged; D003131:Combined Modality Therapy; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000628:therapy*; D004311:Double-Blind Method; D054855:Drug-Eluting Stents / Q000009:adverse effects; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011108:Polymers; D011474:Prosthesis Design; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015607:Stents / Q000009:adverse effects
chemical_list: D007166:Immunosuppressive Agents; D010975:Platelet Aggregation Inhibitors; D011108:Polymers; C518022:umirolimus; D020123:Sirolimus