Management of resistant hypertension: aldosterone antagonists or intensification of diuretic therapy?

Nephrology (Carlton). 2015 Aug;20(8):567-71. doi: 10.1111/nep.12475.

Abstract

Objective: No consensus has been established as to which is the best fourth-line agent in patients with resistant hypertension (RHT). The aim of the present study was to assess the effect of intensifying diuretic treatment with loop diuretic (furosemide) or aldosterone antagonist (spironolactone) on blood pressure (BP) control in RHT.

Methods: The study population comprised 30 patients with RHT who were divided into two treatment arms. Fifteen patients received furosemide 40 mg/day and 15 patients received spironolactone 25 mg/day. Ambulatory BP monitoring was performed baseline, 3 and 6 months.

Results: Baseline BP was 162 ± 8/90 ± 6 mmHg, 70% men, mean age 63.3 ± 9.1 years 56.1% diabetic and estimated glomerular filtration rate (eGFR) 55.8 ± 16.5 mL/min per 1.73 m(2) . There were no significant differences between groups at baseline in age, gender, percentage diabetics, eGFR, BP, number of antihypertensive drugs, or aldosterone levels. At 6 months, systolic BP decreased by 24 ± 9.2 mmHg (from 163.6 ± 8.6 to 139.6 ± 8.1 mmHg) in the spironolactone group, compared with 13.8 ± 2.8 mmHg (from 162 ± 7.9 to 148 ± 6.4 mmHg) in the furosemide group (P < 0.01). Diastolic BP fell 11 ± 8.1 mmHg in the spironolactone group compared with 5.2 ± 2.2 mmHg in the furosemide group (P < 0.01). Significant reduction in urinary albumin creatinine ratio (from 173 ± 268 to 14 ± 24 mg/g, P < 0.01) was observed in the spironolactone group at 6 months. Multiple regression analysis showed that only treatment with spironolactone was associated with control of BP < 140/90 mmHg at 6 months. No severe adverse events were recorded.

Conclusion: Spironolactone is more effective than furosemide for control of BP in RHT patients, with a positive added effect on albuminuria. Spironolactone is safe in patients with mild kidney impairment, although serum potassium should be closely monitored, especially in diabetics.

Keywords: diuretics; furosemide; resistant hypertension; spironolactone.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Aged
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects*
  • Blood Pressure Monitoring, Ambulatory
  • Drug Resistance*
  • Drug Therapy, Combination
  • Female
  • Furosemide / adverse effects
  • Furosemide / therapeutic use*
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Kidney / drug effects
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / adverse effects
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Prospective Studies
  • Sodium Potassium Chloride Symporter Inhibitors / adverse effects
  • Sodium Potassium Chloride Symporter Inhibitors / therapeutic use*
  • Spironolactone / adverse effects
  • Spironolactone / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Mineralocorticoid Receptor Antagonists
  • Sodium Potassium Chloride Symporter Inhibitors
  • Spironolactone
  • Furosemide