Spironolactone in congestive heart failure refractory to high-dose loop diuretic and low-dose angiotensin-converting enzyme inhibitor

Am J Cardiol. 1993 Jan 21;71(3):21A-28A. doi: 10.1016/0002-9149(93)90241-4.


Patients with severe congestive heart failure (New York Heart Association [NYHA] functional classes III-IV) often can tolerate only low doses of angiotensin-converting enzyme (ACE) inhibitors because pronounced hypotension caused by additional ACE inhibitor increments may decrease renal perfusion. The use of high-dose loop diuretics is currently advised to overcome diuretic resistance in refractory congestive heart failure (CHF). In a baseline controlled study, we evaluated 21 patients with diuretic resistance and evident fluid retention for the responses to 5 days of double drug therapy consisting of high-dose loop diuretic (10 mg oral bumetanide) in combination with the maximum tolerable dose of an ACE inhibitor (individualized to blood pressure and kidney function). Five patients (24%) showed a gross natriuresis and reduction in excess weight > 25% in response to this therapy. The remaining 16 patients (76%) with insufficient responses (i.e., < 25% reduction in excess weight) subsequently received 100 mg spironolactone once a day for 7 days in addition to the double therapy. Spironolactone coadministration was highly effective in 13 of 16 patients (81%). Marked natriuresis and diuresis were achieved within the next week of treatment, and CHF symptoms regressed or disappeared. The clinical course was similar in the bumetanide-ACE inhibitor and the bumetanide-ACE inhibitor-spironolactone treatment (triple therapy) groups. Plasma aldosterone was significantly higher (p < 0.05) in the patients who needed spironolactone. The 3 patients who were considered refractory to triple therapy exhibited the highest baseline plasma aldosterone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Bumetanide / administration & dosage
  • Bumetanide / therapeutic use*
  • Drug Resistance
  • Drug Therapy, Combination
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Renin-Angiotensin System / drug effects
  • Spironolactone / therapeutic use*
  • Water-Electrolyte Balance / drug effects


  • Angiotensin-Converting Enzyme Inhibitors
  • Bumetanide
  • Spironolactone