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

J Renin Angiotensin Aldosterone Syst. 2015 Sep;16(3):599-613. doi: 10.1177/1470320315575849. Epub 2015 Mar 17.

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.

Keywords: Mineralocorticoid receptor antagonists; aldosterone; cardiovascular actions; chronic kidney disease; meta-analysis; safety; systematic review.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Blood Pressure / drug effects
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / physiopathology
  • Carotid Intima-Media Thickness
  • Creatinine / blood
  • Diastole / drug effects
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology
  • Glomerular Filtration Rate
  • Heart Ventricles / drug effects
  • Heart Ventricles / pathology
  • Heart Ventricles / physiopathology
  • Humans
  • Hyperkalemia / blood
  • Hyperkalemia / complications
  • Mineralocorticoid Receptor Antagonists / adverse effects
  • Mineralocorticoid Receptor Antagonists / pharmacology
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Organ Size / drug effects
  • Oxidative Stress / drug effects
  • Potassium / blood
  • Publication Bias
  • Randomized Controlled Trials as Topic*
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / physiopathology
  • Stroke Volume / drug effects
  • Systole / drug effects
  • Vascular Stiffness / drug effects

Substances

  • Mineralocorticoid Receptor Antagonists
  • Creatinine
  • Potassium