title: Perhexiline improves symptomatic status in elderly patients with severe aortic stenosis.
abstract: BACKGROUND
  The prognosis of severe symptomatic aortic stenosis is poor without aortic valve replacement, with no previous reports of beneficial effects of any medical treatment on either symptoms or outcome. However, this condition is increasingly a disease of the elderly and cardiothoracic surgery is associated with significant mortality and morbidity in this group.
  
  
  OBJECTIVE
  We postulated that perhexiline, a novel anti-ischaemic agent with an oxygen-sparing metabolic effect in the myocardium (via inhibition of carnitine palmitoyltransferase-1) and no adverse haemodynamic effects, may improve symptomatic status in elderly patients with severe aortic stenosis. We report here our initial experience with perhexiline treatment in such patients.
  
  
  METHODS
  Elderly patients with symptomatic severe aortic stenosis, who were deemed unsuitable for aortic valve replacement, were treated with perhexiline, the drug dosage titrated according to steady state plasma perhexiline concentrations. NYHA functional class was determined prior to and three months following commencement of perhexiline, and changes were analysed using McNemar's test.
  
  
  RESULTS
  Fifteen patients, age range 73-87, were followed for up to 30 months (median 18 months). Symptomatic status improved in 13 of the 15 patients over the first three months of perhexiline therapy (p < 0.01), five patients becoming asymptomatic. Twelve month actuarial survival was 80% (95% CI = 57, 100). Perhexiline was well tolerated, with no withdrawals due to toxicity or deteriorating clinical status.
  
  
  CONCLUSIONS
  Therapy with perhexiline was associated with a marked improvement in clinical status in this group of elderly patients with severe aortic stenosis.
authors.affiliation: Cardiology Unit, Queen Elizabeth Hospital, North Western Adelaide Health Service, University of Adelaide, SA.
authors.forename: S A
authors.initials: SA
authors.lastname: Unger
authors.forename: M A
authors.initials: MA
authors.lastname: Robinson
authors.forename: J D
authors.initials: JD
authors.lastname: Horowitz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000188:drug therapy*; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D010480:Perhexiline / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D002317:Cardiovascular Agents; D010480:Perhexiline