Cardiovascular actions of mineralocorticoid receptor antagonists in patients with chronic kidney disease: A systematic review and meta-analysis of randomized trials

Abstract

Introduction: The safety and actions of mineralocorticoid receptor antagonists on surrogate markers of cardiovascular disease as well as major patient level cardiovascular end-points in patients with chronic kidney disease are unclear. Methods: MEDLINE, EMBASE, Trip Database, Cochrane Central Register of Controlled Trials, Cochrane Renal Group specialized register, Current Controlled Trials and clinicaltrials.gov were searched for relevant trials. Results: Twenty-nine trials (1581 patients) were included. Overall, mineralocorticoid receptor antagonists lowered both systolic and diastolic blood pressure (–5.24, 95% confidence interval (CI) –8.65, −1.82 mmHg; p=0.003 and −1.96, 95% CI −3.22, –0.69 mmHg; p=0.002 respectively). There were insufficient data to perform a meta-analysis of other cardiovascular effects. However, a systematic review of the studies included suggested a consistent improvement in surrogate markers of cardiovascular disease. Overall, the use of mineralocorticoid receptor antagonists was associated with an increased serum potassium (0.23, 95% CI 0.13, 0.33 mmol/l; p<0.0001) and higher risk ratio (1.76, 95% CI 1.20, 2.57; p=0.001) of hyperkalemia. Data on long-term cardiovascular outcomes and mortality were not available in any of the trials. Conclusions: The long-term effects of mineralocorticoid receptor antagonists on cardiovascular events, mortality and safety need to be established.

Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: a systematic review and meta-analysis

“…These findings are in keeping with previous published meta-analyses [15, 16, 20]. By using additional unpublished summary results from a number of authors, we ensure that our protein/albumin excretion data are more comprehensive and hence more accurate.…”

“…The beneficial effects on outcomes were confounded by increased risk of hyperkalaemia, a factor limiting MRA prescribing in CKD [17–19]. Similar findings were described in a more recent meta-analysis on the cardiovascular actions of MRAs in CKD [20]. However, the conclusions of these analyses are drawn from mainly published proteinuria data only, derived by consolidating disparate urinary protein excretion measures used in different trials (variably reported as protein or albumin excretion in spot samples or 24 h collections).…”

“…We cannot draw conclusions regarding longer-term safety and efficacy of combination MRA and/or ARB, despite postulated CV benefits of reducing protein/albumin excretion [53]. This is in keeping with a meta-analysis published last year [20]. …”

“…1). Full text assessment of 56 articles resulted in selection of 19 eligible trials including 1646 patients [22–31, 34, 36–43], more than were included in the previously published meta-analyses [15, 16, 20]. Authors were contacted for unpublished data; we obtained supplemental summarised results for ten trials [23, 26–30, 39, 40, 42, 43].…”

Safety and cardiovascular effects of mineralocorticoid receptor antagonists for patients receiving hemodialysis: a systematic review and meta-analysis

“…Interestingly, Ng et al found in their meta-analysis of 28 studies that the use of MR antagonists was associated with increased serum potassium and a higher risk ratio of hyperkalemia. 35 A possible explanation is that Ng included patients with chronic kidney disease (CKD) of stage I to stage V, while this review only included patients receiving hemodialysis.…”