The safety of eplerenone in hemodialysis patients: A noninferiority randomized controlled trial

Clinical Journal of the American Society of Nephrology

Volumn 10, Issue 9, 2015, Pages 1602-1608

  Walsh, Michael ^a,b   Manns, Braden ^c,d   Garg, Amit X ^e   Bueti, Joe ^f   Rabbat, Christian ^b   Smyth, Andrew ^a   Tyrwhitt, Jessica ^a   Bosch, Jackie ^a   Gao, Peggy ^a   Devereaux, P J ^a,b   Wald, Ron ^g,h  

^a MCMASTER UNIVERSITY   (Canada)

^b MCMASTER UNIVERSITY   (Canada)

^c UNIVERSITY OF CALGARY   (Canada)

^d UNIVERSITY OF CALGARY   (Canada)

^e UNIVERSITY OF WESTERN ONTARIO   (Canada)

^f UNIVERSITY OF MANITOBA   (Canada)

^g ST MICHAEL'S HOSPITAL   (Canada)

^h ST MICHAEL'S HOSPITAL   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; EPLERENONE; PLACEBO; POTASSIUM; SPIRONOLACTONE; MINERALOCORTICOID ANTAGONIST;

ADULT; AGED; ARTICLE; CONTROLLED STUDY; DIABETES MELLITUS; DRUG WITHDRAWAL; FEMALE; HEMODIALYSIS; HUMAN; HYPERKALEMIA; HYPERTENSION; HYPOTENSION; KIDNEY POLYCYSTIC DISEASE; MAJOR CLINICAL STUDY; MALE; PATIENT SAFETY; RANDOMIZED CONTROLLED TRIAL; SENSITIVITY ANALYSIS; TREATMENT OUTCOME; ANALOGS AND DERIVATIVES; BLOOD; BLOOD PRESSURE; CHEMICALLY INDUCED; CLINICAL TRIAL; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; KIDNEY FAILURE, CHRONIC; MIDDLE AGED; MULTICENTER STUDY; PATHOPHYSIOLOGY; PILOT STUDY; TREATMENT WITHDRAWAL;

AGED; BLOOD PRESSURE; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; HUMANS; HYPERKALEMIA; HYPOTENSION; KIDNEY FAILURE, CHRONIC; MALE; MIDDLE AGED; MINERALOCORTICOID RECEPTOR ANTAGONISTS; PILOT PROJECTS; POTASSIUM; RENAL DIALYSIS; SPIRONOLACTONE; WITHHOLDING TREATMENT;

EID: 84941202657     PISSN: 15559041     EISSN: 1555905X     Source Type: Journal    
DOI: 10.2215/CJN.12371214     Document Type: Article

References (30)

1. Harnett JD, Kent GM, Barre PE, Taylor R, Parfrey PS: Risk factors for the development of left ventricular hypertrophy in a prospectively followed cohort of dialysis patients. J AmSocNephrol 4: 1486–1490, 1994
2. Foley RN, Curtis BM, Randell EW, Parfrey PS: Left ventricular hypertrophy in new hemodialysis patients without symptomatic cardiac disease. Clin J Am Soc Nephrol 5: 805–813, 2010
3. Foley RN: Clinical epidemiology of cardiac disease in dialysis patients: Left ventricular hypertrophy, ischemic heart disease, and cardiac failure. Semin Dial 16: 111–117, 2003
4. Foley RN, Collins AJ: End-stage renal disease in the United States: An update from the United States Renal Data System. J AmSoc Nephrol 18: 2644–2648, 2007
5. Sato A, Funder JW, Saruta T: Involvement of aldosterone in left ventricular hypertrophy of patients with end-stage renal failure treated with hemodialysis. Am J Hypertens 12: 867–873, 1999
6. Brilla CG, Maisch B: Regulation of the structural remodelling of the myocardium: fromhypertrophy to heart failure. Eur Heart J 15 [Suppl D]: 45–52, 1994
7. Brilla CG, Matsubara LS, Weber KT: Antifibrotic effects of spironolactone in preventing myocardial fibrosis in systemic arterial hypertension. Am J Cardiol 71: 12A–16A, 1993
8. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J; Randomized Aldactone Evaluation Study Investigators: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 341: 709–717, 1999
9. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M; Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators: Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 348: 1309–1321, 2003
10. Pitt B, Reichek N, Willenbrock R, Zannad F, Phillips RA, Roniker B, Kleiman J, Krause S, Burns D, Williams GH: Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: The 4E-left ventricular hypertrophy study. Circulation 108: 1831–1838, 2003
11. Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Harty B, Heitner JF, Kenwood CT, Lewis EF, O’Meara E, Probstfield JL, Shaburishvili T, Shah SJ, Solomon SD, Sweitzer NK, Yang S, McKinlay SM; TOPCAT Investigators: Spironolactone for heart failurewith preserved ejection fraction. NEngl J Med 370: 1383–1392, 2014
12. Frankenfield DL, Weinhandl ED, Powers CA, Howell BL, Herzog CA, St Peter WL: Utilization and costs of cardiovascular disease medications in dialysis patients in Medicare Part D. Am J Kidney Dis 59: 670–681, 2012
13. Berry C, McMurray JJV: Serious adverse events experienced by patients with chronic heart failure taking spironolactone. Heart 85: E8, 2001
14. Teo KK, Pfeffer M, Mancia G, O’Donnell M, Dagenais G, Diaz R, Dans A, Liu L, Bosch J, Joseph P, Copland I, Jung H, Pogue J, Yusuf S; Aliskiren Prevention of Later Life Outcomes trial Investigators: Aliskiren alone or with other antihypertensives in the elderly with borderline and stage 1 hypertension: The APOLLO trial. Eur Heart J 35: 1743–1751, 2014
15. Jones B, Jarvis P, Lewis JA, Ebbutt AF: Trials to assess equivalence: The importance of rigorous methods. BMJ 313: 36–39, 1996
16. Gross E, Rothstein M, Dombek S, Juknis HI: Effect of spironolactone on blood pressure and the renin-angiotensin-aldosterone system in oligo-anuric hemodialysis patients. Am J Kidney Dis 46: 94–101, 2005
17. Hussain S, Dreyfus DE, Marcus RJ, BiedermanRWW, McGill RL: Is spironolactone safe for dialysis patients? Nephrol Dial Transplant 18: 2364–2368, 2003
18. Ito Y, Mizuno M, Suzuki Y, Tamai H, Hiramatsu T, Ohashi H, Ito I, Kasuga H, Horie M, Maruyama S, Yuzawa Y, Matsubara T, Matsuo S; Nagoya Spiro Study Group: Long-term effects of spironolactone in peritoneal dialysis patients. J AmSoc Nephrol 25: 1094–1102, 2014
19. Matsumoto Y, Kageyama S, Yakushigawa T, Arihara K, Sugiyama T, Mori Y, Sugiyama H, Ohmura H, Shio N: Long-term low-dose spironolactone therapy is safe in oligoanuric hemodialysis patients. Cardiology 114: 32–38, 2009
20. Matsumoto Y, Mori Y, Kageyama S, Arihara K, Sugiyama T, Ohmura H, Yakushigawa T, Sugiyama H, Shimada Y, Nojima Y, Shio N: Spironolactone reduces cardiovascular and cerebrovascularmorbidity and mortality in hemodialysis patients. J AmColl Cardiol 63: 528–536, 2014
21. Saudan P, Mach F, Perneger T, Schnetzler B, Stoermann C, Fumeaux Z, Rossier M, Martin PY: Safety of low-dose spironolactone administration in chronic haemodialysis patients. Nephrol Dial Transplant 18: 2359–2363, 2003
22. Taheri S, Mortazavi M, Shahidi S, Pourmoghadas A, Garakyaraghi M, Seirafian S, Eshaghian A, Ghassami M: Spironolactone in chronic hemodialysis patients improves cardiac function. Saudi J Kidney Dis Transpl 20: 392–397, 2009
23. Vukusich A, Kunstmann S, Varela C, Gainza D, Bravo S, Sepulveda D, Cavada G, Michea L, Marusic ET: A randomized, double-blind, placebo-controlled trial of spironolactone on carotid intima-media thickness in nondiabetic hemodialysis patients. Clin J Am Soc Nephrol 5: 1380–1387, 2010
24. Shavit L, Neykin D, Lifschitz M, Slotki I: Effect of eplerenone on blood pressure and the renin-angiotensin-aldosterone system in oligo-anuric chronic hemodialysis patients—a pilot study. Clin Nephrol 76: 388–395, 2011
25. Agarwal R, Sinha AD, Pappas MK, Abraham TN, Tegegne GG: Hypertension in hemodialysis patients treated with atenolol or lisinopril: A randomized controlled trial. Nephrol Dial Transplant 29: 672–681, 2014
26. Knoll GA, Sahgal A, Nair RC, Graham J, van Walraven C, Burns KD: Renin-angiotensin system blockade and the risk of hyperkalemia in chronic hemodialysis patients. Am J Med 112: 110–114, 2002
27. Iitake K, Kimura T, Matsui K, Ota K, Shoji M, Inoue M, Yoshinaga K: Effect of haemodialysis on plasma ADH levels, plasma renin activity and plasma aldosterone levels in patients with end-stage renal disease. Acta Endocrinol (Copenh) 110: 207–213, 1985
28. Kohagura K, Higashiuesato Y, Ishiki T, Yoshi S, Ohya Y, Iseki K, Takishita S: Plasma aldosterone in hypertensive patients on chronic hemodialysis: Distribution, determinants and impact on survival. Hypertens Res 29: 597–604, 2006
29. Vasan RS, Evans JC, Benjamin EJ, Levy D, Larson MG, Sundstrom J, Murabito JM, Sam F, Colucci WS, Wilson PW: Relations of serum aldosterone to cardiac structure: Gender-related differences in the Framingham Heart Study. Hypertension 43: 957–962, 2004
30. Yasuda G, Shibata K, Takizawa T, Ikeda Y, Tokita Y, Umemura S, Tochikubo O: Prevalence of constipation in continuous ambulatory peritoneal dialysis patients and comparison with hemodialysis patients. Am J Kidney Dis 39: 1292–1299, 2002