Effects of Spironolactone and Chlorthalidone on Cardiovascular Structure and Function in Chronic Kidney Disease.

Abstract

Background and objectives: In a randomized double blind, placebo controlled trial, treatment with spironolactone in early-stage chronic kidney disease, reduced left ventricular mass and arterial stiffness compared to placebo. It is not known if these effects were due to blood pressure reduction or specific vascular and myocardial effects of spironolactone. Design, setting, participants and measurements: A prospective, randomized, open-label, blinded endpoint (PROBE) study conducted in four UK centers (Birmingham, Cambridge, Edinburgh & London) comparing spironolactone 25mg to chlorthalidone 25mg once daily for 40 weeks in 154 participants with non diabetic stage 2 and 3 chronic kidney disease (eGFR 30-89ml/min/1.73m2). The primary endpoint was change in left ventricle mass on cardiac magnetic resonance. Participants were on treatment with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker and had controlled blood pressure (target ≤130/80mmHg). Results: There was no significant difference in left ventricular mass regression; at week 40 the adjusted mean difference for spironolactone compared to chlorthalidone was -3.8g (95% CI - 8.1g, 0.5g), p=0.08. Office and 24-hour ambulatory blood pressures 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 to chlorthalidone was 0.04m/s (-0.4m/s, 0.5m/s), p=0.9. Hyperkalemia (defined ≥5.4mEq/L) occurred more frequently with spironolactone (12 vs. 2 participants, adjusted relative risk was 5.5 (1.4, 22.1), p=0.02), but there were no cases of severe hyperkalemia (defined ≥6.5mEq/L). A decline in eGFR >30% occurred in 8 participants treated with chlorthalidone compared with 2 participants with spironolactone (adjusted relative risk was 0.2 (0.05, 1.1), p=0.07). Conclusion: Spironolactone was not superior to chlorthalidone in reducing left ventricular mass, blood pressure or arterial stiffness in non-diabetic CKD.