Serum concentration of potassium in chronic heart failure patients administered spironolactone plus furosemide and either enalapril maleate, losartan potassium or candesartan cilexetil

J Clin Pharm Ther. 2005 Dec;30(6):603-10. doi: 10.1111/j.1365-2710.2005.00694.x.


Objective: To retrospectively investigate elevation of serum potassium when spironolactone (25 or 50 mg/day) and furosemide were administered concomitantly with an angiotensin II converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB) to patients with chronic heart failure for 12 months and occurrence of hyperkalemia and hypokalemia because of concomitant administration of spironolactone plus an ACE-I or ARB and furosemide.

Methods: Patients with chronic heart failure, who visited departments of cardiovascular internal medicine and cardiovascular surgery at the National Hospital Organization Osaka Medical Center, were enrolled for this study. Serum potassium, blood urea nitrogen (BUN), serum creatinine, uric acid, and serum sodium were determined in every patient at the time of start of treatment and at 3 and 12 months of treatment. Data from patients in Groups A (25 mg/day spironolactone + 40 mg/day furosemide + an ACE-I or ARB) and B (50 mg/day spironolactone + 40 mg/day furosemide + an ACE-I or ARB) were analysed for differences with respect to the ACE-I and ARB used.

Results: When 50 mg/day spironolactone plus 5 mg/day enalapril maleate (enalapril) or 50 mg/day losartan potassium (losartan) or 8 mg/day candesartan cilexetil (candesartan) plus 40 mg/day furosemide were concomitantly used, the mean value of serum potassium was significantly elevated only in the group treated with 50 mg/day spironolactone regardless of the concomitant drug. The number of patients with hyperkalemia (>5.5 mEq/L) at 12 months of treatment was 12 (8.8%), while the number of patients with hypokalemia (<or=3.5 mEq/L) was 7 (5.1%). However, the occurrence of hyperkalemia was almost the same regardless of the dose of spironolactone or the ACE-I or ARB concomitantly administered. Therefore, if enalapril, losartan, or candesartan is concomitantly used, it is necessary to monitor the serum concentration of potassium, even if spironolactone is administered at a dose of 25 mg/day.

Conclusion: The occurrence of hyperkalemia in patients administered spironolactone is influenced by the dose, but when it is used concomitantly with enalapril, losartan or candesartan, the occurrence of hyperkalemia exceeding 5.5 mEq/L may increase even if the dose of spironolactone is as low as 25 mg. Thus it is essential to always monitor serum potassium.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antihypertensive Agents / therapeutic use
  • Diuretics / adverse effects*
  • Diuretics / therapeutic use
  • Drug Therapy, Combination
  • Enalapril / therapeutic use
  • Female
  • Furosemide / therapeutic use
  • Heart Failure / drug therapy
  • Heart Failure / metabolism*
  • Humans
  • Hyperkalemia / chemically induced*
  • Losartan / therapeutic use
  • Male
  • Middle Aged
  • Potassium / blood*
  • Sodium Potassium Chloride Symporter Inhibitors / therapeutic use
  • Spironolactone / adverse effects*
  • Spironolactone / therapeutic use


  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Diuretics
  • Sodium Potassium Chloride Symporter Inhibitors
  • Spironolactone
  • Enalapril
  • Furosemide
  • Losartan
  • Potassium