Nicola C Edwards1,2, Anna M Price3,4, Samir Mehta5, Thomas F Hiemstra6,7, Amreen Kaur3, Peter J Greasley8, David J Webb9, Neeraj Dhaun9,10, Iain M MacIntyre9,10, Tariq Farrah9,10, Vanessa Melville9, Anna S Herrey11, Gemma Slinn5, Rebekah Wale5, Natalie Ives5, David C Wheeler12,13, Ian Wilkinson6,7, Richard P Steeds3,14, Charles J Ferro3,4, Jonathan N Townend3,14. 1. Institute of Cardiovascular Sciences, University of Birmingham, United Kingdom Nicolaed@adhb.govt.co.nz. 2. Department of Cardiology, Green Lane Cardiovascular Unit, Auckland, New Zealand. 3. Institute of Cardiovascular Sciences, University of Birmingham, United Kingdom. 4. Department of Nephrology, Queen Elizabeth Hospital, Birmingham, United Kingdom. 5. Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom. 6. Cambridge Clinical Trials Unit, Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom. 7. GlaxoSmithKline, England, United Kingdom. 8. Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. 9. Center for Cardiovascular Science and Clinical Research Center, University of Edinburgh, United Kingdom. 10. Department of Nephrology, National Health Services Lothian, Edinburgh, United Kingdom. 11. UCL Institute of Cardiovascular Science and Department of Cardiology, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom. 12. Department of Renal Medicine, University College London, United Kingdom. 13. George Institute for Global Health, Sydney, Australia. 14. Department of Cardiology, Queen Elizabeth Hospital Birmingham, United Kingdom.
Abstract
BACKGROUND AND OBJECTIVES: In a randomized double-blind, placebo-controlled trial, treatment with spironolactone in early-stage CKD reduced left ventricular mass and arterial stiffness compared with placebo. It is not known if these effects were due to BP reduction or specific vascular and myocardial effects of spironolactone. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A prospective, randomized, open-label, blinded end point study conducted in four UK centers (Birmingham, Cambridge, Edinburgh, and London) comparing spironolactone 25 mg to chlorthalidone 25 mg once daily for 40 weeks in 154 participants with nondiabetic stage 2 and 3 CKD (eGFR 30-89 ml/min per 1.73 m2). The primary end point was change in left ventricular mass on cardiac magnetic resonance imaging. Participants were on treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and had controlled BP (target ≤130/80 mm Hg). RESULTS: There was no significant difference in left ventricular mass regression; at week 40, the adjusted mean difference for spironolactone compared with chlorthalidone was -3.8 g (95% confidence interval, -8.1 to 0.5 g, P=0.08). Office and 24-hour ambulatory BPs fell in response to both drugs with no significant differences between treatment. Pulse wave velocity was not significantly different between groups; at week 40, the adjusted mean difference for spironolactone compared with chlorthalidone was 0.04 m/s (-0.4 m/s, 0.5 m/s, P=0.90). Hyperkalemia (defined ≥5.4 mEq/L) occurred more frequently with spironolactone (12 versus two participants, adjusted relative risk was 5.5, 95% confidence interval, 1.4 to 22.1, P=0.02), but there were no patients with severe hyperkalemia (defined ≥6.5 mEq/L). A decline in eGFR >30% occurred in eight participants treated with chlorthalidone compared with two participants with spironolactone (adjusted relative risk was 0.2, 95% confidence interval, 0.05 to 1.1, P=0.07). CONCLUSIONS: Spironolactone was not superior to chlorthalidone in reducing left ventricular mass, BP, or arterial stiffness in nondiabetic CKD.
BACKGROUND AND OBJECTIVES: In a randomized double-blind, placebo-controlled trial, treatment with spironolactone in early-stage CKD reduced left ventricular mass and arterial stiffness compared with placebo. It is not known if these effects were due to BP reduction or specific vascular and myocardial effects of spironolactone. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A prospective, randomized, open-label, blinded end point study conducted in four UK centers (Birmingham, Cambridge, Edinburgh, and London) comparing spironolactone 25 mg to chlorthalidone 25 mg once daily for 40 weeks in 154 participants with nondiabetic stage 2 and 3 CKD (eGFR 30-89 ml/min per 1.73 m2). The primary end point was change in left ventricular mass on cardiac magnetic resonance imaging. Participants were on treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and had controlled BP (target ≤130/80 mm Hg). RESULTS: There was no significant difference in left ventricular mass regression; at week 40, the adjusted mean difference for spironolactone compared with chlorthalidone was -3.8 g (95% confidence interval, -8.1 to 0.5 g, P=0.08). Office and 24-hour ambulatory BPs fell in response to both drugs with no significant differences between treatment. Pulse wave velocity was not significantly different between groups; at week 40, the adjusted mean difference for spironolactone compared with chlorthalidone was 0.04 m/s (-0.4 m/s, 0.5 m/s, P=0.90). Hyperkalemia (defined ≥5.4 mEq/L) occurred more frequently with spironolactone (12 versus two participants, adjusted relative risk was 5.5, 95% confidence interval, 1.4 to 22.1, P=0.02), but there were no patients with severe hyperkalemia (defined ≥6.5 mEq/L). A decline in eGFR >30% occurred in eight participants treated with chlorthalidone compared with two participants with spironolactone (adjusted relative risk was 0.2, 95% confidence interval, 0.05 to 1.1, P=0.07). CONCLUSIONS: Spironolactone was not superior to chlorthalidone in reducing left ventricular mass, BP, or arterial stiffness in nondiabetic CKD.
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Authors: Manvir K Hayer; Nicola C Edwards; Gemma Slinn; William E Moody; Rick P Steeds; Charles J Ferro; Anna M Price; Cecilio Andujar; Mary Dutton; Rachel Webster; David J Webb; Scott Semple; Iain MacIntyre; Vanessa Melville; Ian B Wilkinson; Thomas F Hiemstra; David C Wheeler; Anna Herrey; Margaret Grant; Samir Mehta; Natalie Ives; Jonathan N Townend Journal: Am Heart J Date: 2017-05-24 Impact factor: 4.749
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