Spironolactone – is it still useful in clinical practice? Review article
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Published:
Dec 31, 2015
Keywords:
spironolactone, aldosterone, eplerenone, mineralocorticoid receptor antagonists, hypertension, heart failure, primary aldosteronism
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Abstract
Mineralocorticoid receptor antagonists are commonly used in the treatment of cardiovascular diseases. There are some notable differences between two drugs of this group, spironolactone and eplerenone. Spironolactone is more potent and longer acting but may be less tolerated by some patients due to its antiandrogenic and progestogenic side effects. Both drugs are effective in the treatment of hypertension, primary aldosteronism, and heart failure but comparisons are difficult due to the absence of large comparative outcome trials. In the present paper, evidence regarding the use of spironolactone in patients with cardiovascular disease was summarized, particularly in the context of comparison between spironolactone and its newer competitor – eplerenone, in order to guide clinical decision making regarding the choice of mineralocorticoid receptor antagonist.
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Jędrusik , P. (2015). Spironolactone – is it still useful in clinical practice?. Medycyna Faktow (J EBM), 8(4(29), 33-44. Retrieved from https://journalsmededu.pl/index.php/jebm/article/view/2280
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References
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2. Struthers A., Krum H., Williams G.H.: A comparison of the aldosterone-blocking agents eplerenone and spironolactone. Clin. Cardiol. 2008; 31: 153-158.
3. Maron B.A., Leopold J.A.: Aldosterone antagonists: effective but often forgotten. Circulation 2010; 121: 934-939.
4. Tykarski A., Narkiewicz K., Gaciong Z. et al.: Zasady postępowania w nadciśnieniu tętniczym – 2015 rok. Wytyczne Polskiego Towarzystwa Nadciśnienia Tętniczego. Nadciśnienie Tętnicze 2015 (w druku).
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6. Jeunemaitre X., Chatellier G., Kreft-Jais C. et al.: Efficacy and tolerance of spironolactone in essential hypertension. Am. J. Cardiol. 1987; 60: 820-825.
7. Nishizaka M.K., Zaman M.A., Calhoun D.A.: Efficacy of low-dose spironolactone in subjects with resistant hypertension. Am. J. Hypertens. 2003; 16: 925-930.
8. Adlin E.V., Marks A.D., Channick B.J.: Spironolactone and hydrochlorothiazide in essential hypertension. Arch. Intern. Med. 1972; 130: 855-858.
9. Kreeft J.H., Larochelle P., Ogilive R.I.: Comparison of chlorthalidone and spironolactone in low-renin essential hypertension. Can. Med. Assoc. J. 1983; 128: 31-34.
10. Karlberg B.E., Kagedal B., Tegler L. et al.: Controlled treatment of primary hypertension with propranolol and spironolactone. A crossover study with special reference to initial plasma renin activity. Am. J. Cardiol. 1976; 37: 642-649.
11. Henry M., Wehrlen M., Pelletier B. et al.: Spironolactone versus nifedipine in essential hypertension. Am. J. Cardiol. 1990; 65: 36K-38K.
12. Plouin P.F., Battaglia C., Alhenc-Gélas F. et al.: Are angiotensin converting enzyme inhibition and aldosterone antagonism equivalent in hypertensive patients over fifty? Am. J. Hypertens. 1991; 4: 356-362.
13. Weinberger M.H., Roniker B., Krause S.L. et al.: Eplerenone, a selective aldosterone blocker, in mild-to-moderate hypertension. Am. J. Hypertens. 2002; 15: 709-716.
14. Catena C., Colussi G.L., Lapenna R. et al.: Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism. Hypertension 2007; 50: 911-918.
15. Gaddam K., Corros C., Pimenta E. et al.: Rapid reversal of left ventricular hypertrophy and intracardiac volume overload in patients with resistant hypertension and hyperaldosteronism: a prospective clinical study. Hypertension 2010; 55: 1137-1142.
16. Sato A., Suzuki Y., Saruta T.: Effects of spironolactone and angiotensin-converting enzyme inhibitor on left ventricular hypertrophy in patients with essential hypertension. Hypertens. Res. 1999; 22: 17-22.
17. Taniguchi I., Kawai M., Date T. et al.: Effects of spironolactone during an angiotensin II receptor blocker treatment on the left ventricular mass reduction in hypertensive patients with concentric left ventricular hypertrophy. Circ. J. 2006; 70: 995-1000.
18. Chapman N., Dobson J., Wilson S. et al.: Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension 2007; 49: 1-7.
19. Vaclavik J., Sedlak R., Plachy M. et al.: Addition of spironolactone in patients with resistant arterial hypertension (ASPIRANT): a randomized, double-blind, placebo-controlled trial. Hypertension 2011; 57: 1069-1075.
20. Rodilla E., Costa J.A., Perez-Lahiguera F. et al.: Spironolactone and doxazosin treatment in patients with resistant hypertension. Rev. Esp. Cardiol. 2009; 62: 158-166.
21. Viera A.J.: Resistant hypertension. J. Am. Board Fam. Med. 2012; 25: 487-495.
22. Parthasarathy K.H., Menard J., White W.B.: A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism. J. Hypertens. 2011; 29: 980-990.
23. Karagiannis A., Tziomalos K., Papageorgiou A. et al.: Spironolactone versus eplerenone for the treatment of idiopathic hyperaldosteronism. Expert Opin. Pharmacother. 2008; 9: 509-515.
24. Fourkiotis V., Vonend O., Diederich S. et al.: Effectiveness of eplerenone or spironolactone treatment in preserving renal function in primary aldosteronism. Eur. J. Endocrinol. 2013; 168: 75-81.
25. Pitt B., Zannad F., Remme W.J. et al.: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N. Engl. J. Med. 1999; 341: 709-717.
26. Hamaguchi S., Kinugawa S., Tsuchihashi-Makaya M. et al.: Spironolactone use at discharge was associated with improved survival in hospitalized patients with systolic heart failure. Am. Heart J. 2010; 160: 1156-1162.
27. Vizzardi E., Nodari S., Caretta G. et al.: Effects of spironolactone on long-term mortality and morbidity in patients with heart failure and mild or no symptoms. Am. J. Med. Sci. 2014; 347: 271-276.
28. Hayashi M., Tsutamoto T., Wada A. et al.: Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents postinfarct left ventricular remodeling associated with suppression of a marker of myocardial collagen synthesis in patients with first anterior acute myocardial infarction. Circulation 2003; 107: 2559-2565.
29. 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.
30. Zannad F., McMurray J.J.V., Krum H. et al.: Eplerenone in patients with systolic heart failure and mild symptoms. N. Engl. J. Med. 2011; 364: 11-21.
31. McMurray J.J.V., Adamopoulos S., Anker S.D. et al.: ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012. Eur. Heart J. 2012; 33: 1787-1847.
32. Yancy C.W., Jessup M., Bozkurt B. et al.: 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013; 128: e240-e327.
33. Chatterjee S., Moeller C., Shah N. et al.: Eplerenone is not superior to older and less expensive aldosterone antagonists. Am. J. Med. 2012; 125: 817-825.
34. Yamaji M., Tsutamoto T., Kawahara C. et al.: Effect of eplerenone versus spironolactone on cortisol and hemoglobin A1c levels in patients with chronic heart failure. Am. Heart J. 2010; 160: 915-921.
35. Roongsritong C., Sutthiwan P., Bradley J. et al.: Spironolactone improves diastolic function in the elderly. Clin. Cardiol. 2005; 28: 484-487.
36. Sato A., Hayashi M., Saruta T.: Relative long-term effects of spironolactone in conjunction with angiotensin-converting enzyme inhibitors on left ventricular mass and diastolic function in patients with essential hypertension. Hypertens. Res. 2002; 25: 837-842.
37. Gupta A., Schiros C.G., Gaddam K.K. et al.: Effect of spironolactone on diastolic function in hypertensive left ventricular hypertrophy. J. Hum. Hypertens. 2015; 29: 241-246.
38. Edelmann F., Wachter R., Schmidt A.G. 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.
39. Pitt B., Pfeffer M.A., Assmann S.F. et al.: Spironolactone for heart failure with preserved ejection fraction. N. Engl. J. Med. 2014; 370: 1383-1392.
40. Pfeffer M.A., Claggett B., Assmann S.F.et al.: Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. Circulation 2015; 131: 34-42.
41. Zile M.R., Gaasch W.H.: UpToDate: Treatment and prognosis of diastolic heart failure, 2014.
42. Williams R.S., deLemos J.A., Dimas V. et al.: Effect of spironolactone on patients with atrial fibrillation and structural heart disease. Clin. Cardiol. 2011; 34: 415-419.
43. Gaddam K., Pimenta E., Thomas S.J. et al.: Spironolactone reduces severity of obstructive sleep apnoea in patients with resistant hypertension: a preliminary report. J. Hum. Hypertens. 2010; 24: 532-537.
44. Bianchi S., Bigazzi R., Campese V.M.: Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int. 2006; 70: 2116-2123.
45. Navaneethan S.D., Nigwekar S.U., Sehgal A.R. et al.: Aldosterone antagonists for preventing the progression of chronic kidney disease: a systematic review and meta-analysis. Clin. J. Am. Soc. Nephrol. 2009; 4: 542-551.
46. Schjoedt K.J., Rossing K., Juhl T.R. et al.: Beneficial impact of spironolactone on nephrotic range albuminuria in diabetic nephropathy. Kidney Int. 2006; 70: 536-542.
47. Oxlund C., Henriksen J., Tarnow L. et al.: Low dose spironolactone reduces blood pressure in patients with resistant hypertension and type 2 diabetes mellitus: a double blind randomised clinical trial. J. Hypertens. 2013; 31: 2094-2102.
48. Bomback A.S., Muskala P., Bald E. et al:. Low-dose spironolactone, added to long-term ACE inhibitor therapy, reduces blood pressure and urinary albumin excretion in obese patients with hypertensive target organ damage. Clin. Nephrol. 2009; 72: 449-456.
49. Unger T., Paulis L., Sica D.A.: Therapeutic perspectives in hypertension: novel means for renin-angiotensin-aldosterone system modulation and emerging device-based approaches. Eur. Heart J. 2011; 32: 2739-2747.
2. Struthers A., Krum H., Williams G.H.: A comparison of the aldosterone-blocking agents eplerenone and spironolactone. Clin. Cardiol. 2008; 31: 153-158.
3. Maron B.A., Leopold J.A.: Aldosterone antagonists: effective but often forgotten. Circulation 2010; 121: 934-939.
4. Tykarski A., Narkiewicz K., Gaciong Z. et al.: Zasady postępowania w nadciśnieniu tętniczym – 2015 rok. Wytyczne Polskiego Towarzystwa Nadciśnienia Tętniczego. Nadciśnienie Tętnicze 2015 (w druku).
5. Batterink J., Stabler S.N., Tejani A.M., Fowkes C.T.: Spironolactone for hypertension. Cochrane Database of Systematic Reviews 2010, Issue 8. Art. No.: CD008169 [doi: 10.1002/14651858.CD008169.pub2].
6. Jeunemaitre X., Chatellier G., Kreft-Jais C. et al.: Efficacy and tolerance of spironolactone in essential hypertension. Am. J. Cardiol. 1987; 60: 820-825.
7. Nishizaka M.K., Zaman M.A., Calhoun D.A.: Efficacy of low-dose spironolactone in subjects with resistant hypertension. Am. J. Hypertens. 2003; 16: 925-930.
8. Adlin E.V., Marks A.D., Channick B.J.: Spironolactone and hydrochlorothiazide in essential hypertension. Arch. Intern. Med. 1972; 130: 855-858.
9. Kreeft J.H., Larochelle P., Ogilive R.I.: Comparison of chlorthalidone and spironolactone in low-renin essential hypertension. Can. Med. Assoc. J. 1983; 128: 31-34.
10. Karlberg B.E., Kagedal B., Tegler L. et al.: Controlled treatment of primary hypertension with propranolol and spironolactone. A crossover study with special reference to initial plasma renin activity. Am. J. Cardiol. 1976; 37: 642-649.
11. Henry M., Wehrlen M., Pelletier B. et al.: Spironolactone versus nifedipine in essential hypertension. Am. J. Cardiol. 1990; 65: 36K-38K.
12. Plouin P.F., Battaglia C., Alhenc-Gélas F. et al.: Are angiotensin converting enzyme inhibition and aldosterone antagonism equivalent in hypertensive patients over fifty? Am. J. Hypertens. 1991; 4: 356-362.
13. Weinberger M.H., Roniker B., Krause S.L. et al.: Eplerenone, a selective aldosterone blocker, in mild-to-moderate hypertension. Am. J. Hypertens. 2002; 15: 709-716.
14. Catena C., Colussi G.L., Lapenna R. et al.: Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism. Hypertension 2007; 50: 911-918.
15. Gaddam K., Corros C., Pimenta E. et al.: Rapid reversal of left ventricular hypertrophy and intracardiac volume overload in patients with resistant hypertension and hyperaldosteronism: a prospective clinical study. Hypertension 2010; 55: 1137-1142.
16. Sato A., Suzuki Y., Saruta T.: Effects of spironolactone and angiotensin-converting enzyme inhibitor on left ventricular hypertrophy in patients with essential hypertension. Hypertens. Res. 1999; 22: 17-22.
17. Taniguchi I., Kawai M., Date T. et al.: Effects of spironolactone during an angiotensin II receptor blocker treatment on the left ventricular mass reduction in hypertensive patients with concentric left ventricular hypertrophy. Circ. J. 2006; 70: 995-1000.
18. Chapman N., Dobson J., Wilson S. et al.: Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension 2007; 49: 1-7.
19. Vaclavik J., Sedlak R., Plachy M. et al.: Addition of spironolactone in patients with resistant arterial hypertension (ASPIRANT): a randomized, double-blind, placebo-controlled trial. Hypertension 2011; 57: 1069-1075.
20. Rodilla E., Costa J.A., Perez-Lahiguera F. et al.: Spironolactone and doxazosin treatment in patients with resistant hypertension. Rev. Esp. Cardiol. 2009; 62: 158-166.
21. Viera A.J.: Resistant hypertension. J. Am. Board Fam. Med. 2012; 25: 487-495.
22. Parthasarathy K.H., Menard J., White W.B.: A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism. J. Hypertens. 2011; 29: 980-990.
23. Karagiannis A., Tziomalos K., Papageorgiou A. et al.: Spironolactone versus eplerenone for the treatment of idiopathic hyperaldosteronism. Expert Opin. Pharmacother. 2008; 9: 509-515.
24. Fourkiotis V., Vonend O., Diederich S. et al.: Effectiveness of eplerenone or spironolactone treatment in preserving renal function in primary aldosteronism. Eur. J. Endocrinol. 2013; 168: 75-81.
25. Pitt B., Zannad F., Remme W.J. et al.: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N. Engl. J. Med. 1999; 341: 709-717.
26. Hamaguchi S., Kinugawa S., Tsuchihashi-Makaya M. et al.: Spironolactone use at discharge was associated with improved survival in hospitalized patients with systolic heart failure. Am. Heart J. 2010; 160: 1156-1162.
27. Vizzardi E., Nodari S., Caretta G. et al.: Effects of spironolactone on long-term mortality and morbidity in patients with heart failure and mild or no symptoms. Am. J. Med. Sci. 2014; 347: 271-276.
28. Hayashi M., Tsutamoto T., Wada A. et al.: Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents postinfarct left ventricular remodeling associated with suppression of a marker of myocardial collagen synthesis in patients with first anterior acute myocardial infarction. Circulation 2003; 107: 2559-2565.
29. 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.
30. Zannad F., McMurray J.J.V., Krum H. et al.: Eplerenone in patients with systolic heart failure and mild symptoms. N. Engl. J. Med. 2011; 364: 11-21.
31. McMurray J.J.V., Adamopoulos S., Anker S.D. et al.: ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012. Eur. Heart J. 2012; 33: 1787-1847.
32. Yancy C.W., Jessup M., Bozkurt B. et al.: 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013; 128: e240-e327.
33. Chatterjee S., Moeller C., Shah N. et al.: Eplerenone is not superior to older and less expensive aldosterone antagonists. Am. J. Med. 2012; 125: 817-825.
34. Yamaji M., Tsutamoto T., Kawahara C. et al.: Effect of eplerenone versus spironolactone on cortisol and hemoglobin A1c levels in patients with chronic heart failure. Am. Heart J. 2010; 160: 915-921.
35. Roongsritong C., Sutthiwan P., Bradley J. et al.: Spironolactone improves diastolic function in the elderly. Clin. Cardiol. 2005; 28: 484-487.
36. Sato A., Hayashi M., Saruta T.: Relative long-term effects of spironolactone in conjunction with angiotensin-converting enzyme inhibitors on left ventricular mass and diastolic function in patients with essential hypertension. Hypertens. Res. 2002; 25: 837-842.
37. Gupta A., Schiros C.G., Gaddam K.K. et al.: Effect of spironolactone on diastolic function in hypertensive left ventricular hypertrophy. J. Hum. Hypertens. 2015; 29: 241-246.
38. Edelmann F., Wachter R., Schmidt A.G. 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.
39. Pitt B., Pfeffer M.A., Assmann S.F. et al.: Spironolactone for heart failure with preserved ejection fraction. N. Engl. J. Med. 2014; 370: 1383-1392.
40. Pfeffer M.A., Claggett B., Assmann S.F.et al.: Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. Circulation 2015; 131: 34-42.
41. Zile M.R., Gaasch W.H.: UpToDate: Treatment and prognosis of diastolic heart failure, 2014.
42. Williams R.S., deLemos J.A., Dimas V. et al.: Effect of spironolactone on patients with atrial fibrillation and structural heart disease. Clin. Cardiol. 2011; 34: 415-419.
43. Gaddam K., Pimenta E., Thomas S.J. et al.: Spironolactone reduces severity of obstructive sleep apnoea in patients with resistant hypertension: a preliminary report. J. Hum. Hypertens. 2010; 24: 532-537.
44. Bianchi S., Bigazzi R., Campese V.M.: Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int. 2006; 70: 2116-2123.
45. Navaneethan S.D., Nigwekar S.U., Sehgal A.R. et al.: Aldosterone antagonists for preventing the progression of chronic kidney disease: a systematic review and meta-analysis. Clin. J. Am. Soc. Nephrol. 2009; 4: 542-551.
46. Schjoedt K.J., Rossing K., Juhl T.R. et al.: Beneficial impact of spironolactone on nephrotic range albuminuria in diabetic nephropathy. Kidney Int. 2006; 70: 536-542.
47. Oxlund C., Henriksen J., Tarnow L. et al.: Low dose spironolactone reduces blood pressure in patients with resistant hypertension and type 2 diabetes mellitus: a double blind randomised clinical trial. J. Hypertens. 2013; 31: 2094-2102.
48. Bomback A.S., Muskala P., Bald E. et al:. Low-dose spironolactone, added to long-term ACE inhibitor therapy, reduces blood pressure and urinary albumin excretion in obese patients with hypertensive target organ damage. Clin. Nephrol. 2009; 72: 449-456.
49. Unger T., Paulis L., Sica D.A.: Therapeutic perspectives in hypertension: novel means for renin-angiotensin-aldosterone system modulation and emerging device-based approaches. Eur. Heart J. 2011; 32: 2739-2747.