title: Safety and efficacy of angiotensin-converting enzyme inhibitors in symptomatic severe aortic stenosis: Symptomatic Cardiac Obstruction-Pilot Study of Enalapril in Aortic Stenosis (SCOPE-AS).
abstract: BACKGROUND
  Animal models have demonstrated a benefit of angiotensin-converting enzyme inhibitors (ACEI) in experimental aortic stenosis (AS), and intravenous nitroprusside has shown hemodynamic improvements in AS with left ventricular (LV) dysfunction. Although routinely used in most heart failure situations, ACEI are avoided in AS because of the risk of hypotension. We aimed to determine the clinical tolerance and efficacy of the ACEI enalapril in the setting of symptomatic severe AS.
  
  
  METHODS
  Patients with symptomatic severe AS were enrolled in a randomized, double-blinded, controlled trial to enalapril or placebo arms after initial stabilization. Standard antifailure medications were continued. Enalapril was started at 2.5 mg bid and increased to 10 mg bid. The primary end points were development of hypotension and improvements in Borg dyspnea index and 6-minute walk distance at 1 month. Secondary end points were minor ACEI intolerance, cough, presyncope, improvement in New York Heart Association class, and echocardiographic parameters.
  
  
  RESULTS
  Fifty-six patients were enrolled (37 in the enalapril arm and 19 in the placebo arm). Enalapril was tolerated without hypotension or syncope when LV systolic function was preserved. Three of 5 patients with LV dysfunction and congestive heart failure had hypotension and were withdrawn. Patients who tolerated enalapril (n = 34) demonstrated significant improvement in NYHA class, Borg index (5.4 +/- 1.2 vs 5.6 +/- 1.7, P =.03), and 6-minute walk distance (402 +/- 150 vs 376 +/- 174, P =.003) compared with control subjects. Within the enalapril group, patients with associated regurgitant lesions improved the most.
  
  
  CONCLUSIONS
  ACEI are well tolerated in symptomatic patients with severe AS. Patients with congestive heart failure with LV dysfunction and low normal blood pressure are prone to have hypotension. Enalapril significantly improves effort tolerance and reduces dyspnea in symptomatic AS.
authors.affiliation: Department of Cardiology, Madras Medical College and Research Institute, Chennai, India. drcanands@yahoo.co.in
authors.forename: Anand
authors.initials: A
authors.lastname: Chockalingam
authors.forename: S
authors.initials: S
authors.lastname: Venkatesan
authors.forename: T
authors.initials: T
authors.lastname: Subramaniam
authors.forename: V
authors.initials: V
authors.lastname: Jagannathan
authors.forename: S
authors.initials: S
authors.lastname: Elangovan
authors.forename: R
authors.initials: R
authors.lastname: Alagesan
authors.forename: G
authors.initials: G
authors.lastname: Gnanavelu
authors.forename: Smrita
authors.initials: S
authors.lastname: Dorairajan
authors.forename: B P
authors.initials: BP
authors.lastname: Krishna
authors.forename: V
authors.initials: V
authors.lastname: Chockalingam
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001024:Aortic Valve Stenosis / Q000145:classification / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004656:Enalapril / Q000009:adverse effects / Q000627:therapeutic use*; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril