SAFETY AND EFFICACY OF EPLERENONE IN PATIENTS AT HIGH RISK FOR HYPERKALEMIA AND/OR WORSENING RENAL FUNCTION. ANALYSES OF THE EMPHASIS-HF STUDY SUBGROUPS (EPLERENONE IN MILD PATIENTS HOSPITALIZATION AND SURVIVAL STUDY IN HEART FAILURE)

Translation articles:

R. Eschalier, J.J.V. McMurray, K. Swedberg, D.J. van Veldhuisen, H. Krum, S.J. Pocock, H. Shi, J. Vincent, P. Rossignol, F. Zannad, B. Pitt, for the EMPHASIS-HF Investigators “Safety and Efficacy of Eplerenone in Patients at High Risk for Hyperkalemia and/or Worsening Renal Function. Analyses of the EMPHASIS-HF Study Subgroups (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure)”  J Am Coll Cardiol 2013;62(17):1585-93; http://dx.doi.org/10.1016/j.jacc.2013.04.086

1. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999;341:709-17.

2. Zannad F, McMurray JJV, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011;364:11-21.

3. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348:1309-21.

4. McMurray JJV, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2012;14:803-69.

5. Albert NM, Yancy CW, Liang L, et al. Use of aldosterone antagonists in heart failure. JAMA 2009;302:1658-65.

6. Zannad F, McMurray JJV, Drexler H, et al. Rationale and design of the Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure (EMPHASIS-HF). Eur J Heart Fail 2010;12:617-22.

7. Weidmann P, De Myttenaere-Bursztein S, Maxwell MH, De Lima J. Effect on aging on plasma renin and aldosterone in normal man. Kidney Int 1975;8:325-33.

8. Henschkowski J, Stuck AE, Frey BM, et al. Age-dependent decrease in 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity in hypertensive patients. Am J Hypertens 2008;21:644-9.

9. Krug AW, Allenhöfer L, Monticone R, et al. Elevated mineralocorticoid receptor activity in aged rat vascular smooth muscle cells promotes a proinflammatory phenotype via extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase and epidermal growth factor receptor-dependent pathways. Hypertension 2010;55:1476-83.

10. Johnson ES, Weinstein JR, Thorp ML, et al. Predicting the risk of hyperkalemia in patients with chronic kidney disease starting lisinopril. Pharmacoepidemiol Drug Saf 2010;19:266-72.

11. Preiss D, Van Veldhuisen DJ, Sattar N, et al. Eplerenone and newonset diabetes in patients with mild heart failure: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF). Eur J Heart Fail 2012;14:909-15.

12. Ma TK-W, Szeto C-C. Mineralocorticoid receptor antagonist for renal protection. Ren Fail 2012;34:810-7.

13. Funder JW. Aldosterone and mineralocorticoid receptors: orphan questions. Kidney Int 2000;57:1358-63.

14. Bianchi S, Bigazzi R, Campese VM. Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int 2006;70:2116-23.

15. Bomback AS, Kshirsagar AV, Amamoo MA, Klemmer PJ. Change in proteinuria after adding aldosterone blockers to ACE inhibitors or angiotensin receptor blockers in CKD: a systematic review. Am J Kidney Dis 2008;51:199-211.

16. Vardeny O, Wu DH, Desai A, et al. Influence of baseline and worsening renal function on efficacy of spironolactone in patients with severe heart failure. J Am Coll Cardiol 2012;60:2082-9.

17. Mak G, Murphy NF, Ali A, et al. Multiple neurohumoral modulating agents in systolic dysfunction heart failure: are we lowering blood pressure too much? J Card Fail 2008;14:555-60.

18. Juurlink DN, Mamdani MM, Lee DS, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 2004;351:543-51.

19. Muzzarelli S, Maeder MT, Toggweiler S, et al. Frequency and predictors of hyperkalemia in patients _60 years of age with heart failure undergoing intense medical therapy. Am J Cardiol 2012;109:693-8.

20. Chamsi-Pasha MAR, Dupont M, Tang WH. Contemporary administration of aldosterone receptor antagonists in patients hospitalized with congestive heart failure after EMPHASIS-HF. J Am Coll Cardiol 2012;59:E890.

21. Pfisterer M, Buser P, Rickli H, et al. BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIMECHF) randomized trial. JAMA 2009;301:383-92.

22. McMurray JJV, O’Meara E. Treatment of heart failure with spironolactonedtrial and tribulations. N Engl J Med 2004;351:526-8.