From a clinician’s point of view. Knowledge in a nutshell. Spironolactone – why is it worth using and in whom? Review article
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Published:
Sep 30, 2015
Keywords:
spironolactone, hypertension, heart failure, resistant hypertension, atrial fibrillation
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Abstract
In the last two decades, a lot of attention has focused on the role of spironolactone in therapy of hypertension and cardiovascular disease. It is commonly used in the treatment of hypertension, with or without aldosteronism, and of various forms of heart failure. The Randomized Aldactone Evaluation Studies demonstrated that adding spironolactone to a standard therapy significantly reduced morbidity and mortality in patients with moderate to severe heart failure. Cardiac benefits of spironolactone are now sufficiently well established to warrant routine use of these compounds for treatment of patients in moderate to advanced stages of heart failure. Moreover, it is used in the treatment of resistant forms of hypertension. Spironolactone is a commonly used add-on diuretic that provides incremental benefit for salt-and-water excretion. Although spironolactone is highly effective in patients with heart failure and hypertension, the risk of hyperkalaemia should not be overlooked. These risks can be mitigated through appropriate patient selection and education, dose selection and monitoring potassium concentration.
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Olszewski , R. (2015). From a clinician’s point of view. Knowledge in a nutshell. Spironolactone – why is it worth using and in whom?. Cardiology in Practice, 9(3), 23-30. Retrieved from https://journalsmededu.pl/index.php/kwp/article/view/1335
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Copyright: © Medical Education sp. z o.o. This is an Open Access article distributed under the terms of the Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). License (https://creativecommons.org/licenses/by-nc/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
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References
1. Struthers A.D.: Why does spironolactone improve mortality over and above an ACE-inhibitor in chronic heart failure? Br. J. Clin. Pharmacol. 1999; 47: 479-482.
2. McMurray J.J., Adamopoulos S., Anker S.D. 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: 803-869.
3. 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(16): e240-327.
4. Pitt B., Zannad F., Remme W.J. 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: 709-717.
5. 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(4): 271-276.
6. Miura R., Nakamura K., Miura D. et al.: Anti-inflammatory effect of spironolactone on human peripheral blood mononuclear cells. J. Pharmacol. Sci. 2006; 101: 2569.
7. Tsutamoto T., Wada A., Maeda K. et al.: Effect of Spironolactone on Plasma Brain Natriuretic Peptide and Left Ventricular Remodelling in Patients With Congestive Heart Failure. J. Am. Coll. Cardiol. 2001; 37: 1228-1233.
8. Owan T.E., Hodge D.O., Herges R.M. et al.: Trends in prevalence and outcome of heart failure with preserved ejection fraction. N. Engl. J. Med. 2006; 355: 251-259.
9. Tsutsui H., Tsuchihashi M., Takeshita A.: Mortality and readmission of hospitalized patients with congestive heart failure and preserved versus depressed systolic function. Am. J. Cardiol. 200; 88: 530-533.
10. Smith G.L., Masoudi F.A., VaccarinoV. et al.: Outcomes in heart failure patients with preserved ejection fraction: mortality, readmission, and functional decline. J. Am. Coll. Cardiol. 2003; 41: 1510-1518.
11. Pitt B., Pfeffer M.A., Assmann S.F. et al.; TOPCAT Investigators: Spironolactone for heart failure with preserved ejection fraction. N. Engl. J. Med. 2014; 370: 1383-1392.
12. McMurray J.J., O’Connor C.M.: Lessons from the TOPCAT Trial. N. Engl. J. Med. 2014; 370(15): 1453-1454.
13. Rossignol P., Zannad F.: Regional Differences in Heart Failure With Preserved Ejection Fraction Trials: When Nephrology Meets Cardiology but East Does Not Meet West. Circulation 2015; 131: 7-10.
14. Kristensen S.L., Kober L., Jhund P.S. et al: International Geographic Variation in Event Rates in Trials of Heart Failure With Preserved and Reduced Ejection Fraction. Circulation 2015; 131: 43-53.
15. Shah A.M., Clagget B., Sweitzer N.K. et al.: The prognostic importance of impaired systolic function in heart failure with preserved ejection fraction and the impact of spironolactone. Circulation 2015; 132: 402-414.
16. Olszewski R.: Zastosowanie techniki śledzenia markerów akustycznych w ocenie funkcji lewej komory serca. Badania in vivo i in vitro. IPPT Reports on Fundamental Technological Research 2/2012. Warszawa 2012.
17. Cho G.Y., Marwick T.H., Kim H.S. et al.: Global 2-dimensional strain as a new prognosticator in patients with heart failure. J. Am. Coll. Cardiol. 2009; 54: 618-624.
18. Nahum J., Bensaid A., Dussault C. et al.: Impact of longitudinal myocardial deformation on the prognosis of chronic heart failure patients. Circ. Cardiovasc. Imaging 2010; 3: 249-256.
19. Kalam K., Otahal P., Marwick T.H.: Prognostic implications of global LV dysfunction: a systematic review and meta-analysis of global longitudinal strain and ejection fraction. Heart 2014; 100: 1673-1680.
20. Lang R.M., Badano L.P., Victor Mor-Avi J.F. et al.: Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J. Am. Soc. Echocardiogr. 2015; 28: 1-39.
21. Farquharson C.A., Struthers A.D.: Spironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin i/angiotensin ii conversion in patients with chronic heart failure. Circulation 2000; 101: 594-597.
22. Rrossi R., Crupi N., Coppi F. et al.: Importance of the time of initiation of mineralocorticoid receptor antagonists on risk of mortality in patients with heart failure. Journal of Renin-Angiotensin-Aldosterone System 2015; 16: 119-125.
23. Zdrojewski T., Rutkowski M., Bandosz P. et al.: Prevalence and control of cardiovascular risk factors in Poland. Assumptions and objectives of the NATPOL 2011 Survey. Kardiol. Pol. 2013; 71(4): 381-392.
24. Walker W.G., Neaton J.D., Cutler J.A. et al.: Renal function change in hypertensive members of the Multiple Risk Factor Intervention Trial. Racial and treatment effects. The MRFIT Research Group. JAMA 1992; 268(21): 3085-3091.
25. MacMahon S., Peto R., Cutler J. et al.: Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 1990; 335(8692): 765-774.
26. Lewington S., Clarke R., Quizilbash N. et al.: Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360(9349): 1903-1913.
27. Neal B., MacMahon S., Chapman N.; Blood Pressure Lowering Treatment Trialists’ Collaboration Collaboration: Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Lancet 2000; 356(9246): 1955-1964.
28. Kaplan N.M.: Clinical Hypertension. Lippincott Williams& Wilkins 2006.
29. 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.
30. 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.
31. Calhoun D.A., Jones D., Textor S. et al.: Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension 2008; 51: 1403-1419.
32. Mancia G., Fagard R., Narkiewicz K. et al.: 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur. Heart J. 2013; 34: 2159-2219.
33. Shibata H., Itoh H.: Mineralocorticoid receptor-associated hypertension and its organ damage: clinical relevance for resistant hypertension. Am. J. Hypertens. 2010; 25: 514-523.
34. Chapman N., Dobson J., Wilson S. et al.: Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension 2007; 49: 839-845.
35. Václavík J., Sedlák R.J., Jarkovsky J. et al.: Effect of spironolactone in resistant arterial hypertension: a randomized, double-blind, placebo-controlled trial (ASPIRANT-EXT). Medicine (Baltimore) 2014; 93(27): e162.
36. Oxlund C.S., Henriksen J.H., Tranow L. et al.: Low dose spironolactone reduces blood pressure in patients with resistant hypertension and type 2 diabetes mellitus: a double blind randomized clinical trial. J. Hypertens. 2013; 31: 2094-2102.
37. Abolghasmi R., Taziki O.: Efficacy of low dose spironolactone in chronic kidney disease with resistant hypertension. Saudi J. Kidney Dis. Transpl. 2011; 22: 75-78.
38. Guo H., Xiao Q.: Clinical efficacy of spironolactone for resistant hypertension: a meta analysis from randomized controlled clinical trials. Int. J. Clin. Exp. Med. 2015; 8(5): 7270-7278.
39. http://congress365.escardio.org/Search-Results?vgnextkeyword=The+PATHWAY+2+%28The+principal+results+of+the+Prevention+And+Treatment+of+Hypertension+With+Algorithm+based+therapY-+Optimal+treatment+of+drug+resistant+hypertension%29#.Ve6G6KPxE3k.
40. 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; 347: 415-419.
41. Lin C., Zhang Q., Zhang H., Lin A.: Long-Term Effects of Low-Dose Spironolactone on Chronic Dialysis Patients: A Randomized Placebo-Controlled Study. J. Clin. Hypertens. (Greenwich). 2015 Jul. 30 [online: doi: 10.1111/jch.12628].
42. Craft J.: Eplerenone (Inspra), a new aldosterone antagonist for the treatment of systemic hypertension and heart failure. Proc. (Bayl. Univ. Med. Cent.) 2004; 17(2): 217-220.
2. McMurray J.J., Adamopoulos S., Anker S.D. 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: 803-869.
3. 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(16): e240-327.
4. Pitt B., Zannad F., Remme W.J. 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: 709-717.
5. 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(4): 271-276.
6. Miura R., Nakamura K., Miura D. et al.: Anti-inflammatory effect of spironolactone on human peripheral blood mononuclear cells. J. Pharmacol. Sci. 2006; 101: 2569.
7. Tsutamoto T., Wada A., Maeda K. et al.: Effect of Spironolactone on Plasma Brain Natriuretic Peptide and Left Ventricular Remodelling in Patients With Congestive Heart Failure. J. Am. Coll. Cardiol. 2001; 37: 1228-1233.
8. Owan T.E., Hodge D.O., Herges R.M. et al.: Trends in prevalence and outcome of heart failure with preserved ejection fraction. N. Engl. J. Med. 2006; 355: 251-259.
9. Tsutsui H., Tsuchihashi M., Takeshita A.: Mortality and readmission of hospitalized patients with congestive heart failure and preserved versus depressed systolic function. Am. J. Cardiol. 200; 88: 530-533.
10. Smith G.L., Masoudi F.A., VaccarinoV. et al.: Outcomes in heart failure patients with preserved ejection fraction: mortality, readmission, and functional decline. J. Am. Coll. Cardiol. 2003; 41: 1510-1518.
11. Pitt B., Pfeffer M.A., Assmann S.F. et al.; TOPCAT Investigators: Spironolactone for heart failure with preserved ejection fraction. N. Engl. J. Med. 2014; 370: 1383-1392.
12. McMurray J.J., O’Connor C.M.: Lessons from the TOPCAT Trial. N. Engl. J. Med. 2014; 370(15): 1453-1454.
13. Rossignol P., Zannad F.: Regional Differences in Heart Failure With Preserved Ejection Fraction Trials: When Nephrology Meets Cardiology but East Does Not Meet West. Circulation 2015; 131: 7-10.
14. Kristensen S.L., Kober L., Jhund P.S. et al: International Geographic Variation in Event Rates in Trials of Heart Failure With Preserved and Reduced Ejection Fraction. Circulation 2015; 131: 43-53.
15. Shah A.M., Clagget B., Sweitzer N.K. et al.: The prognostic importance of impaired systolic function in heart failure with preserved ejection fraction and the impact of spironolactone. Circulation 2015; 132: 402-414.
16. Olszewski R.: Zastosowanie techniki śledzenia markerów akustycznych w ocenie funkcji lewej komory serca. Badania in vivo i in vitro. IPPT Reports on Fundamental Technological Research 2/2012. Warszawa 2012.
17. Cho G.Y., Marwick T.H., Kim H.S. et al.: Global 2-dimensional strain as a new prognosticator in patients with heart failure. J. Am. Coll. Cardiol. 2009; 54: 618-624.
18. Nahum J., Bensaid A., Dussault C. et al.: Impact of longitudinal myocardial deformation on the prognosis of chronic heart failure patients. Circ. Cardiovasc. Imaging 2010; 3: 249-256.
19. Kalam K., Otahal P., Marwick T.H.: Prognostic implications of global LV dysfunction: a systematic review and meta-analysis of global longitudinal strain and ejection fraction. Heart 2014; 100: 1673-1680.
20. Lang R.M., Badano L.P., Victor Mor-Avi J.F. et al.: Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J. Am. Soc. Echocardiogr. 2015; 28: 1-39.
21. Farquharson C.A., Struthers A.D.: Spironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin i/angiotensin ii conversion in patients with chronic heart failure. Circulation 2000; 101: 594-597.
22. Rrossi R., Crupi N., Coppi F. et al.: Importance of the time of initiation of mineralocorticoid receptor antagonists on risk of mortality in patients with heart failure. Journal of Renin-Angiotensin-Aldosterone System 2015; 16: 119-125.
23. Zdrojewski T., Rutkowski M., Bandosz P. et al.: Prevalence and control of cardiovascular risk factors in Poland. Assumptions and objectives of the NATPOL 2011 Survey. Kardiol. Pol. 2013; 71(4): 381-392.
24. Walker W.G., Neaton J.D., Cutler J.A. et al.: Renal function change in hypertensive members of the Multiple Risk Factor Intervention Trial. Racial and treatment effects. The MRFIT Research Group. JAMA 1992; 268(21): 3085-3091.
25. MacMahon S., Peto R., Cutler J. et al.: Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 1990; 335(8692): 765-774.
26. Lewington S., Clarke R., Quizilbash N. et al.: Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360(9349): 1903-1913.
27. Neal B., MacMahon S., Chapman N.; Blood Pressure Lowering Treatment Trialists’ Collaboration Collaboration: Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Lancet 2000; 356(9246): 1955-1964.
28. Kaplan N.M.: Clinical Hypertension. Lippincott Williams& Wilkins 2006.
29. 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.
30. 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.
31. Calhoun D.A., Jones D., Textor S. et al.: Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension 2008; 51: 1403-1419.
32. Mancia G., Fagard R., Narkiewicz K. et al.: 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur. Heart J. 2013; 34: 2159-2219.
33. Shibata H., Itoh H.: Mineralocorticoid receptor-associated hypertension and its organ damage: clinical relevance for resistant hypertension. Am. J. Hypertens. 2010; 25: 514-523.
34. Chapman N., Dobson J., Wilson S. et al.: Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension 2007; 49: 839-845.
35. Václavík J., Sedlák R.J., Jarkovsky J. et al.: Effect of spironolactone in resistant arterial hypertension: a randomized, double-blind, placebo-controlled trial (ASPIRANT-EXT). Medicine (Baltimore) 2014; 93(27): e162.
36. Oxlund C.S., Henriksen J.H., Tranow L. et al.: Low dose spironolactone reduces blood pressure in patients with resistant hypertension and type 2 diabetes mellitus: a double blind randomized clinical trial. J. Hypertens. 2013; 31: 2094-2102.
37. Abolghasmi R., Taziki O.: Efficacy of low dose spironolactone in chronic kidney disease with resistant hypertension. Saudi J. Kidney Dis. Transpl. 2011; 22: 75-78.
38. Guo H., Xiao Q.: Clinical efficacy of spironolactone for resistant hypertension: a meta analysis from randomized controlled clinical trials. Int. J. Clin. Exp. Med. 2015; 8(5): 7270-7278.
39. http://congress365.escardio.org/Search-Results?vgnextkeyword=The+PATHWAY+2+%28The+principal+results+of+the+Prevention+And+Treatment+of+Hypertension+With+Algorithm+based+therapY-+Optimal+treatment+of+drug+resistant+hypertension%29#.Ve6G6KPxE3k.
40. 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; 347: 415-419.
41. Lin C., Zhang Q., Zhang H., Lin A.: Long-Term Effects of Low-Dose Spironolactone on Chronic Dialysis Patients: A Randomized Placebo-Controlled Study. J. Clin. Hypertens. (Greenwich). 2015 Jul. 30 [online: doi: 10.1111/jch.12628].
42. Craft J.: Eplerenone (Inspra), a new aldosterone antagonist for the treatment of systemic hypertension and heart failure. Proc. (Bayl. Univ. Med. Cent.) 2004; 17(2): 217-220.