Login Register Cart 0
Generic placeholder image

Current Vascular Pharmacology

Editor-in-Chief

ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Antihypertensive Therapy in Patients Receiving Maintenance Hemodialysis: A Narrative Review of the Available Clinical-Trial Evidence

Author(s): Panagiotis I. Georgianos and Rajiv Agarwal*

Volume 19, Issue 1, 2021

Published on: 17 March, 2020

Page: [12 - 20] Pages: 9

DOI: 10.2174/1570161118666200317151000

Price: $65

Abstract

Background: Blood pressure (BP)-lowering with the use of antihypertensive drugs appears to protect the cardiovascular (CV) system in hemodialysis patients. However, the optimal treatment algorithm of hypertension remains elusive; extrapolation of clinical-trial evidence from the general population may not be optimal.

Methods: For this narrative review, we searched the Medline/PubMed database (inception to August 01, 2019) to identify randomized clinical trials evaluating the efficacy of antihypertensive drugs on CV outcomes and mortality in patients on hemodialysis.

Results: Randomized trials with angiotensin-converting-enzyme-inhibitors (ACEIs) or angiotensinreceptor- blockers (ARBs) failed to provide consistent cardioprotection. β-blockers may provide a more consistent CV benefit. Although some early clinical trials have shown that mineralocorticoid-receptorantagonists (MRAs) reduce CV mortality, the associated risk of hyperkalemia raises important safety concerns on the use of MRAs as add-on therapy.

Conclusion: Our first-line therapy of hypertension in hemodialysis is the assessment and management of dry-weight and optimization of dialysis prescription. Based on the available clinical-trial evidence, we prescribe atenolol 3 times/week after dialysis as the first-line pharmacological option of hypertension to our patients without specific indications for other agents. Long-acting dihydropyridines and ACEIs/ARBs are our second-line and third-line choices, respectively. We avoid using MRAs and await results from ongoing trials testing their safety and efficacy. In patients receiving maintenance hemodialysis, randomized trials are clearly warranted in order to define BP targets and the comparative effectiveness of different antihypertensive drugs.

Keywords: Antihypertensive drugs, blood pressure, hemodialysis, hypertension, CCB, CI.

« Previous Next »
Graphical Abstract

[1]
Agarwal R, Nissenson AR, Batlle D, Coyne DW, Trout JR, Warnock DG. Prevalence, treatment, and control of hypertension in chronic he-modialysis patients in the United States. Am J Med 2003; 115(4): 291-7.
[http://dx.doi.org/10.1016/S0002-9343(03)00366-8] [PMID: 12967694]
[2]
Agarwal R. Epidemiology of interdialytic ambulatory hypertension and the role of volume excess. Am J Nephrol 2011; 34(4): 381-90.
[http://dx.doi.org/10.1159/000331067] [PMID: 21893975]
[3]
Georgianos PI, Agarwal R. Epidemiology, diagnosis and management of hypertension among patients on chronic dialysis. Nat Rev Nephrol 2016; 12(10): 636-47.
[http://dx.doi.org/10.1038/nrneph.2016.129] [PMID: 27573731]
[4]
Pappaccogli M, Labriola L, Van der Niepen P, et al. Is blood pressure measured correctly in dialysis centres? Physicians’ and patients’ views. Nephrol Dial Transplant 2019; 34(9): 1612-5.
[http://dx.doi.org/10.1093/ndt/gfz125] [PMID: 31302688]
[5]
Rohrscheib MR, Myers OB, Servilla KS, et al. Age-related blood pressure patterns and blood pressure variability among hemodialysis patients. Clin J Am Soc Nephrol 2008; 3(5): 1407-14.
[http://dx.doi.org/10.2215/CJN.00110108] [PMID: 18701616]
[6]
Agarwal R, Peixoto AJ, Santos SF, Zoccali C. Pre- and postdialysis blood pressures are imprecise estimates of interdialytic ambulatory blood pressure. Clin J Am Soc Nephrol 2006; 1(3): 389-98.
[http://dx.doi.org/10.2215/CJN.01891105] [PMID: 17699236]
[7]
Agarwal R, Andersen MJ, Bishu K, Saha C. Home blood pressure monitoring improves the diagnosis of hypertension in hemodialysis patients. Kidney Int 2006; 69(5): 900-6.
[http://dx.doi.org/10.1038/sj.ki.5000145] [PMID: 16518349]
[8]
Agarwal R, Brim NJ, Mahenthiran J, Andersen MJ, Saha C. Out-of-hemodialysis-unit blood pressure is a superior determinant of left ventricular hypertrophy. Hypertension 2006; 47(1): 62-8.
[http://dx.doi.org/10.1161/01.HYP.0000196279.29758.f4] [PMID: 16344376]
[9]
Georgianos PI, Agarwal R. Blood pressure and mortality in long-term hemodialysis-time to move forward. Am J Hypertens 2017; 30(3): 211-22.
[http://dx.doi.org/10.1093/ajh/hpw114] [PMID: 27661097]
[10]
Kalantar-Zadeh K, Kilpatrick RD, McAllister CJ, Greenland S, Kopple JD. Reverse epidemiology of hypertension and cardiovascular death in the hemodialysis population: the 58th annual fall conference and scientific sessions. Hypertension 2005; 45(4): 811-7.
[http://dx.doi.org/10.1161/01.HYP.0000154895.18269.67] [PMID: 15699452]
[11]
Zager PG, Nikolic J, Brown RH, et al. “U” curve association of blood pressure and mortality in hemodialysis patients. Medical Directors of Dialysis Clinic, Inc. Kidney Int 1998; 54(2): 561-9.
[http://dx.doi.org/10.1046/j.1523-1755.1998.00005.x] [PMID: 9690224]
[12]
Agarwal R. Blood pressure and mortality among hemodialysis patients. Hypertension 2010; 55(3): 762-8.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.144899] [PMID: 20083728]
[13]
Alborzi P, Patel N, Agarwal R. Home blood pressures are of greater prognostic value than hemodialysis unit recordings. Clin J Am Soc Nephrol 2007; 2(6): 1228-34.
[http://dx.doi.org/10.2215/CJN.02250507] [PMID: 17942773]
[14]
Bansal N, McCulloch CE, Rahman M, et al. Blood pressure and risk of all-cause mortality in advanced chronic kidney disease and hemodi-alysis: the chronic renal insufficiency cohort study. Hypertension 2015; 65(1): 93-100.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.04334] [PMID: 25287404]
[15]
Agarwal R, Sinha AD. Cardiovascular protection with antihypertensive drugs in dialysis patients: systematic review and meta-analysis. Hypertension 2009; 53(5): 860-6.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.108.128116] [PMID: 19273737]
[16]
Heerspink HJ, Ninomiya T, Zoungas S, et al. Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systematic review and meta-analysis of randomised controlled trials. Lancet 2009; 373(9668): 1009-15.
[http://dx.doi.org/10.1016/S0140-6736(09)60212-9] [PMID: 19249092]
[17]
Agarwal R, Alborzi P, Satyan S, Light RP. Dry-weight reduction in hypertensive hemodialysis patients (DRIP): a randomized, controlled trial. Hypertension 2009; 53(3): 500-7.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.108.125674] [PMID: 19153263]
[18]
Agarwal R, Bouldin JM, Light RP, Garg A. Probing dry-weight improves left ventricular mass index. Am J Nephrol 2011; 33(4): 373-80.
[http://dx.doi.org/10.1159/000326235] [PMID: 21447945]
[19]
Kayikcioglu M, Tumuklu M, Ozkahya M, et al. The benefit of salt restriction in the treatment of end-stage renal disease by haemodialysis. Nephrol Dial Transplant 2009; 24(3): 956-62.
[http://dx.doi.org/10.1093/ndt/gfn599] [PMID: 19004849]
[20]
Munoz Mendoza J, Bayes LY, Sun S, Doss S, Schiller B. Effect of lowering dialysate sodium concentration on interdialytic weight gain and blood pressure in patients undergoing thrice-weekly in-center nocturnal hemodialysis: a quality improvement study. Am J Kidney Dis 2011; 58(6): 956-63.
[http://dx.doi.org/10.1053/j.ajkd.2011.06.030] [PMID: 21875769]
[21]
Tandon T, Sinha AD, Agarwal R. Shorter delivered dialysis times associate with a higher and more difficult to treat blood pressure. Nephrol Dial Transplant 2013; 28(6): 1562-8.
[http://dx.doi.org/10.1093/ndt/gfs597] [PMID: 23348881]
[22]
Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European society of cardiology and the European society of hypertension: the task force for the management of arterial hypertension of the European Society of Cardiology and the European society of hypertension. J Hypertens 2018; 36(10): 1953-2041.
[http://dx.doi.org/10.1097/HJH.0000000000001940] [PMID: 30234752]
[23]
Converse RL Jr, Jacobsen TN, Toto RD, et al. Sympathetic overactivity in patients with chronic renal failure. N Engl J Med 1992; 327(27): 1912-8.
[http://dx.doi.org/10.1056/NEJM199212313272704] [PMID: 1454086]
[24]
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 2014; 29(3): 672-81.
[http://dx.doi.org/10.1093/ndt/gft515] [PMID: 24398888]
[25]
Zannad F, Kessler M, Lehert P, et al. Prevention of cardiovascular events in end-stage renal disease: results of a randomized trial of fosinopril and implications for future studies. Kidney Int 2006; 70(7): 1318-24.
[http://dx.doi.org/10.1038/sj.ki.5001657] [PMID: 16871247]
[26]
Takahashi A, Takase H, Toriyama T, et al. Candesartan, an angiotensin II type-1 receptor blocker, reduces cardiovascular events in patients on chronic haemodialysis--a randomized study. Nephrol Dial Transplant 2006; 21(9): 2507-12.
[http://dx.doi.org/10.1093/ndt/gfl293] [PMID: 16766543]
[27]
Suzuki H, Kanno Y, Sugahara S, et al. Effect of angiotensin receptor blockers on cardiovascular events in patients undergoing hemodialysis: an open-label randomized controlled trial. Am J Kidney Dis 2008; 52(3): 501-6.
[http://dx.doi.org/10.1053/j.ajkd.2008.04.031] [PMID: 18653268]
[28]
Tai DJ, Lim TW, James MT, Manns BJ, Tonelli M, Hemmelgarn BR. Cardiovascular effects of angiotensin converting enzyme inhibition or angiotensin receptor blockade in hemodialysis: a meta-analysis. Clin J Am Soc Nephrol 2010; 5(4): 623-30.
[http://dx.doi.org/10.2215/CJN.07831109] [PMID: 20133488]
[29]
Iseki K, Arima H, Kohagura K, et al. Effects of angiotensin receptor blockade (ARB) on mortality and cardiovascular outcomes in patients with long-term haemodialysis: a randomized controlled trial. Nephrol Dial Transplant 2013; 28(6): 1579-89.
[http://dx.doi.org/10.1093/ndt/gfs590] [PMID: 23355629]
[30]
Cice G, Di Benedetto A, D’Isa S, et al. Effects of telmisartan added to Angiotensin-converting enzyme inhibitors on mortality and morbidity in hemodialysis patients with chronic heart failure a double-blind, placebo-controlled trial. J Am Coll Cardiol 2010; 56(21): 1701-8.
[http://dx.doi.org/10.1016/j.jacc.2010.03.105] [PMID: 21070920]
[31]
Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the american college of cardiology/american heart association task force on clinical practice guidelines. J Am Coll Cardiol 2018; 71(19): e127-248.
[http://dx.doi.org/10.1016/j.jacc.2017.11.006] [PMID: 29146535]
[32]
Rossignol P, Lamiral Z, Frimat L, et al. Hyperkalaemia prevalence, recurrence and management in chronic haemodialysis: a prospective multicentre French regional registry 2-year survey. Nephrol Dial Transplant 2017; 32(12): 2112-8.
[http://dx.doi.org/10.1093/ndt/gfx053] [PMID: 28460113]
[33]
Yusuf AA, Hu Y, Singh B, Menoyo JA, Wetmore JB. Serum potassium levels and mortality in hemodialysis patients: a retrospective cohort study. Am J Nephrol 2016; 44(3): 179-86.
[http://dx.doi.org/10.1159/000448341] [PMID: 27592170]
[34]
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 2002; 112(2): 110-4.
[http://dx.doi.org/10.1016/S0002-9343(01)01068-3] [PMID: 11835948]
[35]
Denker MG, Cohen DL. Antihypertensive medications in end-stage renal disease. Semin Dial 2015; 28(4): 330-6.
[http://dx.doi.org/10.1111/sdi.12369] [PMID: 25877881]
[36]
Georgianos PI, Agarwal R. Pharmacotherapy of hypertension in chronic dialysis patients. Clin J Am Soc Nephrol 2016; 11(11): 2062-75.
[http://dx.doi.org/10.2215/CJN.00870116] [PMID: 27797886]
[37]
Cice G, Ferrara L, D’Andrea A, et al. Carvedilol increases two-year survivalin dialysis patients with dilated cardiomyopathy: a prospective, placebo-controlled trial. J Am Coll Cardiol 2003; 41(9): 1438-44.
[http://dx.doi.org/10.1016/S0735-1097(03)00241-9] [PMID: 12742278]
[38]
Georgianos PI, Agarwal R. Effect of lisinopril and atenolol on aortic stiffness in patients on hemodialysis. Clin J Am Soc Nephrol 2015; 10(4): 639-45.
[http://dx.doi.org/10.2215/CJN.09981014] [PMID: 25784174]
[39]
Georgianos PI, Agarwal R. Aortic stiffness, ambulatory blood pressure, and predictors of response to antihypertensive therapy in hemo-dialysis. Am J Kidney Dis 2015; 66(2): 305-12.
[http://dx.doi.org/10.1053/j.ajkd.2015.01.018] [PMID: 25818679]
[40]
Agarwal R, Lewis R, Davis JL, Becker B. Lisinopril therapy for hemodialysis hypertension: hemodynamic and endocrine responses. Am J Kidney Dis 2001; 38(6): 1245-50.
[http://dx.doi.org/10.1053/ajkd.2001.29221] [PMID: 11728957]
[41]
Agarwal R. Supervised atenolol therapy in the management of hemodialysis hypertension. Kidney Int 1999; 55(4): 1528-35.
[http://dx.doi.org/10.1046/j.1523-1755.1999.00359.x] [PMID: 10201019]
[42]
Tepel M, Hopfenmueller W, Scholze A, Maier A, Zidek W. Effect of amlodipine on cardiovascular events in hypertensive haemodialysis patients. Nephrol Dial Transplant 2008; 23(11): 3605-12.
[http://dx.doi.org/10.1093/ndt/gfn304] [PMID: 18511605]
[43]
London GM, Marchais SJ, Guerin AP, et al. Salt and water retention and calcium blockade in uremia. Circulation 1990; 82(1): 105-13.
[http://dx.doi.org/10.1161/01.CIR.82.1.105] [PMID: 2364508]
[44]
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(10): 709-17.
[http://dx.doi.org/10.1056/NEJM199909023411001] [PMID: 10471456]
[45]
Williams B, MacDonald TM, Morant S, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet 2015; 386(10008): 2059-68.
[http://dx.doi.org/10.1016/S0140-6736(15)00257-3] [PMID: 26414968]
[46]
Matsumoto Y, Mori Y, Kageyama S, et al. Spironolactone reduces cardiovascular and cerebrovascular morbidity and mortality in hemo-dialysis patients. J Am Coll Cardiol 2014; 63(6): 528-36.
[http://dx.doi.org/10.1016/j.jacc.2013.09.056] [PMID: 24184249]
[47]
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) 2016; 18(2): 121-8.
[http://dx.doi.org/10.1111/jch.12628] [PMID: 26224543]
[48]
Quach K, Lvtvyn L, Baigent C, et al. The safety and efficacy of mineralocorticoid receptor antagonists in patients who require dialysis: a systematic review and meta-analysis. Am J Kidney Dis 2016; 68(4): 591-8.
[http://dx.doi.org/10.1053/j.ajkd.2016.04.011] [PMID: 27265777]
[49]
Hammer F, Malzahn U, Donhauser J, et al. A randomized controlled trial of the effect of spironolactone on left ventricular mass in hemodi-alysis patients. Kidney Int 2019; 95(4): 983-91.
[http://dx.doi.org/10.1016/j.kint.2018.11.025] [PMID: 30712923]
[50]
Charytan DM, Himmelfarb J, Ikizler TA, et al. Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): a randomized, placebo-controlled, multiple dosage trial. Kidney Int 2019; 95(4): 973-82.
[http://dx.doi.org/10.1016/j.kint.2018.08.034] [PMID: 30473139]
[51]
Hayashi SY, Seeberger A, Lind B, et al. Acute effects of low and high intravenous doses of furosemide on myocardial function in anuric haemodialysis patients: a tissue doppler study. Nephrol Dial Transplant 2008; 23(4): 1355-61.
[http://dx.doi.org/10.1093/ndt/gfm805] [PMID: 18048421]
[52]
Bragg-Gresham JL, Fissell RB, Mason NA, et al. Diuretic use, residual renal function, and mortality among hemodialysis patients in the Dialysis outcomes and practice pattern study (DOPPS). Am J Kidney Dis 2007; 49(3): 426-31.
[http://dx.doi.org/10.1053/j.ajkd.2006.12.012] [PMID: 17336704]
[53]
Sibbel S, Walker AG, Colson C, Tentori F, Brunelli SM, Flythe J. Association of continuation of loop diuretics at hemodialysis initiation with clinical outcomes. Clin J Am Soc Nephrol 2019; 14(1): 95-102.
[http://dx.doi.org/10.2215/CJN.05080418] [PMID: 30567905]

Rights & Permissions Print Cite
Article Metrics
68
2
© 2024 Bentham Science Publishers | Privacy Policy