Evolving role for mineralocorticoid receptor antagonists in heart failure with preserved ejection fraction

Current Opinion in Cardiology

Volumn 30, Issue 2, 2015, Pages 168-172

  Miller, Robert J H ^a   Howlett, Jonathan G ^a  

^a UNIVERSITY OF CALGARY   (Canada)

Author keywords

Heart failure; Heart failure with preserved ejection fraction; Mineralocorticoid receptor antagonist; Spironolactone

Indexed keywords

ALDOSTERONE ANTAGONIST; MINERALOCORTICOID ANTAGONIST;

CARDIAC PATIENT; CARDIOVASCULAR MORTALITY; CARDIOVASCULAR RISK; DIASTOLIC BLOOD PRESSURE; DRUG EFFECT; ECHOCARDIOGRAPHY; EXERCISE; HEART DEATH; HEART FAILURE WITH PRESERVED EJECTION FRACTION; HEART LEFT VENTRICLE EJECTION FRACTION; HEART LEFT VENTRICLE FILLING PRESSURE; HOSPITALIZATION; HUMAN; HYPERKALEMIA; OUTCOME ASSESSMENT; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW;

EID: 84927749556     PISSN: 02684705     EISSN: 15317080     Source Type: Journal    
DOI: 10.1097/HCO.0000000000000147     Document Type: Review

References (34)

1. Go AS, Mozaffarian D, Roger VL, et al. Heart Disease and Stroke Statistics - 2013 Update: A report from the American Heart Association. Circulation 2013; 127:e6-e245.
2. McMurray JJ, Petrie MC, Murdoch DR, Davie AP. Clinical epidemiology of heart failure: public and private health burden. Eur Heart J 1998; 19 (Suppl P): 9-16.
3. Lindenfeld J, Albert NM, Boehmer JP, et al. HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail 2010; 16:e1-e194.
4. Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 2006; 355:251- 259.
5. Tribouilloy C, Rusinaru D, Mahjoub H, et al. Prognosis of heart failure with preserved ejection fraction: A 5 year prospective population-based study. Eur Heart J 2008; 29:339-347.
6. Bhatia RS, Tu JV, Lee DS, et al. Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med 2006; 355:260- 269.
7. Brilla CG, Janicki JS, Weber KT. Impaired diastolic function and coronary reserve in genetic hypertension. Role of interstitial fibrosis and medial thickening of intramyocardial coronary arteries. Circ Res 1991; 69:107-115.
8. Douglas PS, Tallant B. Hypertrophy, fibrosis and diastolic dysfunction in early canine experimental hypertension. J Am Coll Cardiol 1991; 17:530-536.
9. Cleland JG, Tendera M, Adamus J, et al. The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J 2006; 27:2338-2345.
10. Flather MD, Shibata MC, Coats AJ, et al. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 2005; 26:215-225.
11. Massie BM, Carson PE, McMurray JJ, et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 2008; 359:2456-2467.
12. How to diagnose diastolic heart failure. European Study Group on Diastolic Heart Failure. Eur Heart J 1998; 19:990-1003.
13. Packer M. Can brain natriuretic peptide be used to guide the management of patients with heart failure and a preserved ejection fraction? The wrong way to identify new treatments for a nonexistent disease. Circ Heart Fail 2011; 4:538-540.
14. Carlsen CM, Bay M, Kirk V, et al. Prevalence and prognosis of heart failure with preserved ejection fraction and elevated N-terminal pro brain natriuretic peptide: A 10-year analysis from the Copenhagen Hospital Heart Failure Study. Eur J Heart Fail 2012; 14:240-247.
15. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999; 341:709-717.
16. 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; 348:1309-1321.
17. 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.
18. Edelmann F, Wachter R, Schmidt AG, et al. Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: The Aldo-DHF randomized controlled trial. JAMA 2013; 309:781-791. This trial showed improvements in echocardiographic measures of diastolic function in patients treated with spironolactone compared with placebo. Although it failed to show an improvement in heart failure symptoms, this may be related to relatively fit individuals being included in the study.
19. Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 2014; 370:1383-1392. This randomized controlled trial demonstrated a reduction in heart failure hospitalizations with the use of spironolactone. In addition, in patients with high risk, it showed a potential reduction in cardiovascular mortality.
20. Masoudi FA, Gross CP, Wang Y, et al. Adoption of spironolactone therapy for older patients with heart failure and left ventricular systolic dysfunction in the United States. Circulation 2005; 112:39-47.
21. Juurlink DN, Mamdani MM, Lee DS, et al. Rates of hyper kalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 2004; 351:543-551.
22. Zannad F, Alla F, Dousset B, et al. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: Insights from the randomized aldactone evaluation study (RALES). Rales Investigators. Circulation 2000; 102:2700- 2706.
23. Sato A, Hayashi M, Saruta T. Relative long-term effects of spironolactone in conjunction with an angiotensin-converting enzyme inhibitor on left ventricular mass and diastolic function in patients with essential hypertension. Hypertens Res 2002; 25:837-842.
24. Zhao J, Li J, Li W, et al. Effects of spironolactone on atrial structural remodelling in a canine model of atrial fibrillation produced by prolonged atrial pacing. Brit J Pharmacol 2010; 159:1584-1594.
25. Ohtani T, Ohta M, Yamamoto K, et al. Elevated cardiac tissue level of aldosterone and mineralocorticoid receptor in diastolic heart failure: beneficial effects of mineralocorticoid receptor blocker. Am J Physiol Regul Integr Comp Physiol 2007; 292:R946-R954.
26. Mottram PM, Haluska B, Leano R, et al. Effect of aldosterone antagonism on myocardial dysfunction in hypertensive patients with diastolic heart failure. Circulation 2004; 110:558-565.
27. Williams RS, deLemos JA, Dimas V, et al. Effect of spironolactone on patients with atrial fibrillation and structural heart disease. Clin Cardiol 2011; 34:415- 419.
28. Patel K, Fonarow GC, Kitzman DW, et al. Aldosterone antagonists and outcomes in real-world older patients with heart failure and preserved ejection fraction. JACC Heart Fail 2013; 1:40-47.
29. Lund LH, Benson L, Dahlstrom U, Edner M. Association between use of renin-angiotensin system antagonists and mortality in patients with heart failure and preserved ejection fraction. JAMA 2012; 308:2108- 2117.
30. Shah AM, Shah SJ, Anand IS, et al. Cardiac structure and function in heart failure with preserved ejection fraction: baseline findings from the Echocardiographic Study of the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial. Circ Heart Fail 2014; 7:104-115.
31. Shah AM, Claggett B, Sweitzer NK, et al. Cardiac structure and function and prognosis in heart failure with preserved ejection fraction: Findings from the Echocardiographic Study of the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) Trial. Circ Heart Fail 2014; 7:740-751.
32. Bettencourt P, Ferreira A, Sousa T, et al. Brain natriuretic peptide as a marker of cardiac involvement in hypertension. Int J Cardiol 1999; 69:169- 177.
33. Kolkhof P, Delbeck M, Kretschmer A, et al. Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury. J Cardiovasc Pharmacol 2014; 64:69-78.
34. Pitt B, Kober L, Ponikowski P, et al. Safety and tolerability of the novel nonsteroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: A randomized, double-blind trial. Eur Heart J 2013; 34:2453-2463. Phase II trial showing similar effects on BNP levels between spironolactone and finerenone, but with a lower incidence of hyperkalemia with finerenone.