title: Effect on walking distance and atherosclerosis progression of a nitric oxide-donating agent in intermittent claudication.
abstract: BACKGROUND
  Peripheral arterial disease (PAD) is almost invariably associated with a generalized atherosclerotic involvement of the arterial tree and endothelial dysfunction. Previous short-term studies showed improvement of vascular reactivity and walking capacity in PAD patients by measures aimed at restoring nitric oxide (NO) production. NO is also known to prevent the progression of atherosclerosis. We wished to assess whether the prolonged administration of an NO-donating agent (NCX 4016) improves the functional capacity of PAD patients and affects the progression of atherosclerosis as assessed by carotid intima-media thickness (IMT).
  
  
  METHODS
  This prospective, double-blind, placebo-controlled study enrolled 442 patients with stable intermittent claudication who were randomized to NCX 4016 (800 mg, twice daily) or its placebo for 6 months. The primary study outcome was the absolute claudication distance on a constant treadmill test (10% incline, 3 km/h). The main secondary end point was the change of the mean far-wall right common carotid artery IMT.
  
  
  RESULTS
  The increase of absolute claudication distance at 6 months compared with baseline was 126±140 meters in the placebo-treated group and 117±137 meters in the NCX 4016-treated group, with no significant differences. Carotid IMT increased in the placebo-treated group (+0.01±0.01 mm; P=.55) and decreased in the NCX 4016-treated group (-0.03±0.01 mm; P=.0306). Other secondary end points did not differ between the two treatments.
  
  
  CONCLUSIONS
  Long-term NO donation does not improve the claudication distance but does reduce progression of atherosclerosis in patients with PAD. Further studies aimed at assessing whether long-term NO donation may prevent ischemic cardiovascular events are warranted.
authors.affiliation: Department of Internal Medicine, Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy. grespa@unipg.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Gresele
authors.forename: Rino
authors.initials: R
authors.lastname: Migliacci
authors.forename: Enrico
authors.initials: E
authors.lastname: Arosio
authors.forename: Erminio
authors.initials: E
authors.lastname: Bonizzoni
authors.forename: Pietro
authors.initials: P
authors.lastname: Minuz
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005080:Exercise Test; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D006801:Humans; D007383:Intermittent Claudication / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D011446:Prospective Studies; D016138:Walking / Q000502:physiology*
chemical_list: D005343:Fibrinolytic Agents; D020030:Nitric Oxide Donors; C102148:nitroaspirin; D001241:Aspirin