A Cochrane review included 27 studies with a total of 1 549 subjects. Compared to angiotensin converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARB) plus placebo, non-selective aldosterone antagonists (spirololactone) combined with ACEi and/or ARB (or both) significantly reduced 24 hour proteinuria (MD -0.61 g, 95% CI -1.08 to -0.13;11 studies, n=596; significant heterogeneity, I²= 76%). There was a significant reduction in both systolic (MD -3.44 mm Hg, 95% CI -5.05 to -1.83; 10 studies, n=556) and diastolic (MD -1.73 mm Hg, 95% CI -2.83 to -0.62; 9 studies, n=520) blood pressure with the addition of non-selective aldosterone antagonists to ACEi and/or ARB. This did not translate into a clear improvement in glomerular filtration rate (MD -2.55 mL/min/1.73 m², 95% CI -5.67 to 0.51; 9 studies, n=528). There was a significant increase in the risk of hyperkalaemia with the addition of non-selective aldosterone antagonists to ACEi and/or ARB (RR 2.00, 95% CI 1.25 to 3.20; 11 studies, n=632; number needed to treat for an additional harmful outcome (NNH): 7.2, 95% CI 3.4 to ∞) and increased the risk of gynaecomastia compared to ACEi or ARB (or both) (RR 5.14, 95% CI 1.14 to 23.23; 4 studies, n=281;NNH: 14.1, 95% CI 8.7 to 37.3).
Comment: The quality of evidence is downgraded by study quality (lack of blinding and inadequate intention-to-treat adherence), by indirectness (short follow-up time and only surrogate outcomes), and by imprecise results (limited study size for each comparison).