Is Spironolactone Safe and Effective in the Treatment of Cardiovascular Disease in Mild Chronic Renal Failure - Is Spironolactone Safe and Effective in the Treatment of Cardiovascular Disease in Mild Chronic Renal Failure

Jul 27, 2009
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
British Heart Foundation
Date Published:
01/01/2009
Date Updated:
07/27/2009
Original Posted Date:
07/27/2009
References

Description:

The goal of the trial was to evaluate treatment with spironolactone in addition to an angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin-receptor blocker (ARB) among patients with chronic renal disease.

Hypothesis:

The addition of spironolactone to an ACE-I or ARB would improve left ventricular (LV) mass and arterial stiffness.

Study Design

  • Randomized
  • Parallel

Patients Screened: 2,196
Patients Enrolled: 112
Mean Follow Up: 40 weeks
Mean Patient Age: 54 years
Female: 42%

Patient Populations:

  • 18-80 years of age
  • Stage 2 or 3 chronic kidney disease
  • Treatment with an ACE-I or ARB for at least 6 months
  • Blood pressure <130/85 mm Hg

Exclusions:

  • History of angina
  • Cerebral or peripheral vascular disease
  • Diabetes mellitus
  • Previous hyperkalemia
  • Valvular heart disease
  • Atrial fibrillation
  • Renovascular disease
  • Anemia

Primary Endpoints:

  • LV mass
  • Arterial stiffness measured by PW velocity

Secondary Endpoints:

  • Aortic distensibility
  • Central aortic augmentation pressure and index
  • Blood pressure
  • Albuminuria

Drug/Procedures Used:

After a 4-week run-in phase, patients with chronic renal disease were randomized to spironolactone (n = 56) versus placebo (n = 56) for 36 weeks.

Concomitant Medications:

At baseline, the use of ACE-I was 38%, ARB was 19%, beta-blocker was 15%, calcium antagonist was 13%, and statins were 27%.

Principal Findings:

Overall, 112 patients were randomized. There was no difference in baseline characteristics between the groups. The mean age was 54 years, 43% were women, 72% had hypertension, systolic blood pressure was 130 mm Hg, serum creatinine was 1.5 mg/dl, and the estimated glomerular filtration rate was 49 ml/min/1.73 m2.

At 40 weeks of follow-up, LV mass was improved with spironolactone versus placebo: -14 g versus 3 g (p < 0.01). Pulse-wave (PW) velocity: -0.8 m/s versus -0.1 m/s (p < 0.01), augmentation index: -5.2% versus -1.4% (p < 0.05), and aortic distensibility: 0.69 x 10-3 mm Hg versus 0.04 x 10-3 mm Hg (p < 0.01), systolic blood pressure: -11 mm Hg versus -5 mm Hg (p < 0.05), and albuminuria: -21 mg/mmol versus -8 mg/mmol (p < 0.05), respectively.

Interpretation:

Among patients with stage 2 or 3 chronic renal disease, the addition of spironolactone to an ACE-I or ARB is beneficial. At 40 weeks of follow-up, this therapy reduced LV mass, improved arterial stiffness, reduced blood pressure, and reduced albuminuria. This effect was seen among patients with good blood pressure control and low prevalence of LV hypertrophy. Larger-scale clinical trials are warranted.

References:

Edwards NC, Steeds RP, Stewart PM, Ferro CJ, Townend JN. Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease: a randomized controlled trial. J Am Coll Cardiol 2009;54:505-12.

Keywords: Angiotensin Receptor Antagonists, Follow-Up Studies, Diuretics, Creatinine, Spironolactone, Vascular Stiffness, Angiotensin II Type 1 Receptor Blockers, Glomerular Filtration Rate, Hypertrophy, Renal Insufficiency, Chronic, Hypertension


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