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Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease: a randomized controlled trial.

Author(s): Edwards NC, Steeds RP, Stewart PM, Ferro CJ, Townend JN

Affiliation(s): Department of Cardiology, University Hospital Birmingham and University of Birmingham, Birmingham, UK.

Publication date & source: 2009-08-04, J Am Coll Cardiol., 54(6):505-12.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

OBJECTIVES: We sought to determine whether the addition of spironolactone to angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) improves left ventricular mass and arterial stiffness in early-stage chronic kidney disease (CKD). BACKGROUND: Chronic kidney disease is associated with a high risk of cardiovascular disease and a high prevalence of left ventricular hypertrophy and arterial stiffness that confer an adverse prognosis. It is believed that these abnormalities are in part a result of activation of the renin-angiotensin-aldosterone system. METHODS: After an active run-in phase with spironolactone 25 mg once daily, 112 patients with stage 2 and 3 CKD with good blood pressure control (mean daytime ambulatory blood pressure <130/85 mm Hg) on established treatment with ACE inhibitors or ARBs were randomized to continue spironolactone or to receive a matching placebo. Left ventricular mass (cardiac magnetic resonance) and arterial stiffness (pulse wave velocity/analysis, aortic distensibility) were measured before run in and after 40 weeks of treatment. RESULTS: Compared with placebo, the use of spironolactone resulted in significant improvements in left ventricular mass (-14 +/- 13 g vs. +3 +/- 11 g, p < 0.01), pulse wave velocity (-0.8 +/- 1.0 m/s vs. -0.1 +/- 0.9 m/s, p < 0.01), augmentation index (-5.2 +/- 6.1% vs. -1.4 +/- 5.9%, p < 0.05), and aortic distensibility (0.69 +/- 0.86 x 10(-3) mm Hg vs. 0.04 +/- 1.04 x 10(-3) mm Hg, p < 0.01). CONCLUSIONS: The use of spironolactone reduces left ventricular mass and improves arterial stiffness in early-stage CKD. These effects suggest that aldosterone exerts adverse cardiovascular effects in CKD and that spironolactone is worthy of further study as a treatment that could reduce adverse cardiovascular events. (Is Spironolactone Safe and Effective in the Treatment of Cardiovascular Disease in Mild Chronic Renal Failure; NCT00291720).

Page last updated: 2009-10-20

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