Ahmed M Shaman1,2, Brendan Smyth1,3, Clare Arnott1,4, Suetonia C Palmer5, Anastasia S Mihailidou6,7, Meg J Jardine1,8, Martin P Gallagher1,9, Vlado Perkovic1, Min Jun10. 1. The George Institute for Global Health, Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia. 2. Medication Safety Research Chair, Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. 3. Sydney School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia. 4. Department of Cardiology, The Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. 5. Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand. 6. Department of Cardiology and Kolling Institute, Northern Sydney Local Health District, St. Leonards, New South Wales, Australia. 7. Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia. 8. Department of Renal Medicine, Concord Repatriation General Hospital, Sydney, New South Wales, Australia. 9. Concord Clinical School, Sydney Medical School, Faculty of Health and Medicine, University of Sydney, Sydney, New South Wales, Australia. 10. The George Institute for Global Health, Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia mjun@georgeinstitute.org.au.
Abstract
BACKGROUND AND OBJECTIVES: Elevated BP is an important risk factor for cardiovascular disease, with a prevalence of over 80% in patients undergoing maintenance dialysis. We assessed the comparative BP-lowering efficacy and the safety of BP-lowering drugs in patients undergoing maintenance dialysis. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: We performed a frequentist random effects network meta-analysis of randomized, controlled trials evaluating BP-lowering agents in adult patients undergoing maintenance dialysis. Electronic databases (CENTRAL, MEDLINE, and Embase) were systematically searched (up to August 2018) for relevant trials. The main outcome was systolic BP reduction. RESULTS: Forty trials (4283 participants) met our inclusion criteria. Angiotensin-converting enzyme inhibitors, β-blockers, calcium-channel blockers, and aldosterone antagonists lowered systolic BP to a greater extent than placebo, with effect sizes ranging from -10.8 mm Hg (95% confidence interval, -14.8 to -6.7 mm Hg) for the aldosterone antagonists to -4.3 mm Hg (95% confidence interval, -7.2 to -1.5 mm Hg) for angiotensin-converting enzyme inhibitors. Aldosterone antagonists and β-blockers were superior to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium-channel blockers, and renin inhibitors at lowering systolic BP. Compared with angiotensin-converting enzyme inhibitors, aldosterone antagonists and β-blockers lowered systolic BP by 6.4 mm Hg (95% confidence interval, -11.4 to -1.4 mm Hg) and 4.4 mm Hg (95% confidence interval, -7.4 to -1.3 mm Hg), respectively. Systolic BP reduction was not different with angiotensin receptor blockers, α-blockers, and calcium-channel blockers compared with angiotensin-converting enzyme inhibitors. Renin inhibitors were less effective. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone antagonists incurred risks of drug discontinuation due to adverse events and hypotension. CONCLUSIONS: BP-lowering agents significantly reduced systolic BP in patients undergoing maintenance dialysis. β-Blockers and aldosterone antagonists may confer larger reductions, although treatment with aldosterone antagonists may be limited by adverse events.
BACKGROUND AND OBJECTIVES: Elevated BP is an important risk factor for cardiovascular disease, with a prevalence of over 80% in patients undergoing maintenance dialysis. We assessed the comparative BP-lowering efficacy and the safety of BP-lowering drugs in patients undergoing maintenance dialysis. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: We performed a frequentist random effects network meta-analysis of randomized, controlled trials evaluating BP-lowering agents in adult patients undergoing maintenance dialysis. Electronic databases (CENTRAL, MEDLINE, and Embase) were systematically searched (up to August 2018) for relevant trials. The main outcome was systolic BP reduction. RESULTS: Forty trials (4283 participants) met our inclusion criteria. Angiotensin-converting enzyme inhibitors, β-blockers, calcium-channel blockers, and aldosterone antagonists lowered systolic BP to a greater extent than placebo, with effect sizes ranging from -10.8 mm Hg (95% confidence interval, -14.8 to -6.7 mm Hg) for the aldosterone antagonists to -4.3 mm Hg (95% confidence interval, -7.2 to -1.5 mm Hg) for angiotensin-converting enzyme inhibitors. Aldosterone antagonists and β-blockers were superior to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium-channel blockers, and renin inhibitors at lowering systolic BP. Compared with angiotensin-converting enzyme inhibitors, aldosterone antagonists and β-blockers lowered systolic BP by 6.4 mm Hg (95% confidence interval, -11.4 to -1.4 mm Hg) and 4.4 mm Hg (95% confidence interval, -7.4 to -1.3 mm Hg), respectively. Systolic BP reduction was not different with angiotensin receptor blockers, α-blockers, and calcium-channel blockers compared with angiotensin-converting enzyme inhibitors. Renin inhibitors were less effective. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone antagonists incurred risks of drug discontinuation due to adverse events and hypotension. CONCLUSIONS: BP-lowering agents significantly reduced systolic BP in patients undergoing maintenance dialysis. β-Blockers and aldosterone antagonists may confer larger reductions, although treatment with aldosterone antagonists may be limited by adverse events.
Authors: Matthew A Weir; Stephanie N Dixon; Jamie L Fleet; Matthew A Roberts; Daniel G Hackam; Matthew J Oliver; Rita S Suri; Robert R Quinn; Sundus Ozair; Michael M Beyea; Abhijat Kitchlu; Amit X Garg Journal: J Am Soc Nephrol Date: 2014-10-30 Impact factor: 10.121
Authors: Romina Brignardello-Petersen; M Hassan Murad; Stephen D Walter; Shelley McLeod; Alonso Carrasco-Labra; Bram Rochwerg; Holger J Schünemann; George Tomlinson; Gordon H Guyatt Journal: J Clin Epidemiol Date: 2018-09-22 Impact factor: 6.437
Authors: Rajiv Agarwal; Arjun D Sinha; Maria K Pappas; Terri N Abraham; Getachew G Tegegne Journal: Nephrol Dial Transplant Date: 2014-01-06 Impact factor: 5.992
Authors: David M Charytan; Jonathan Himmelfarb; T Alp Ikizler; Dominic S Raj; Jesse Y Hsu; J Richard Landis; Amanda H Anderson; Adriana M Hung; Rajnish Mehrotra; Shailendra Sharma; Daniel E Weiner; Mark Williams; Marcelo DiCarli; Hicham Skali; Paul L Kimmel; Alan S Kliger; Laura M Dember Journal: Kidney Int Date: 2018-11-23 Impact factor: 10.612
Authors: Michael V Rocco; Robert S Lockridge; Gerald J Beck; Paul W Eggers; Jennifer J Gassman; Tom Greene; Brett Larive; Christopher T Chan; Glenn M Chertow; Michael Copland; Christopher D Hoy; Robert M Lindsay; Nathan W Levin; Daniel B Ornt; Andreas Pierratos; Mary F Pipkin; Sanjay Rajagopalan; John B Stokes; Mark L Unruh; Robert A Star; Alan S Kliger; A Kliger; P Eggers; J Briggs; T Hostetter; A Narva; R Star; B Augustine; P Mohr; G Beck; Z Fu; J Gassman; T Greene; J Daugirdas; L Hunsicker; B Larive; M Li; J Mackrell; K Wiggins; S Sherer; B Weiss; S Rajagopalan; J Sanz; S Dellagrottaglie; M Kariisa; T Tran; J West; M Unruh; R Keene; J Schlarb; C Chan; M McGrath-Chong; R Frome; H Higgins; S Ke; O Mandaci; C Owens; C Snell; G Eknoyan; L Appel; A Cheung; A Derse; C Kramer; N Geller; R Grimm; L Henderson; S Prichard; E Roecker; M Rocco; B Miller; J Riley; R Schuessler; R Lockridge; M Pipkin; C Peterson; C Hoy; A Fensterer; D Steigerwald; J Stokes; D Somers; A Hilkin; K Lilli; W Wallace; B Franzwa; E Waterman; C Chan; M McGrath-Chong; M Copland; A Levin; L Sioson; E Cabezon; S Kwan; D Roger; R Lindsay; R Suri; J Champagne; R Bullas; A Garg; A Mazzorato; E Spanner; M Rocco; J Burkart; S Moossavi; V Mauck; T Kaufman; A Pierratos; W Chan; K Regozo; S Kwok Journal: Kidney Int Date: 2011-07-20 Impact factor: 10.612
Authors: Rajiv Saran; Bruce Robinson; Kevin C Abbott; Lawrence Y C Agodoa; Nicole Bhave; Jennifer Bragg-Gresham; Rajesh Balkrishnan; Xue Dietrich; Ashley Eckard; Paul W Eggers; Abduzhappar Gaipov; Daniel Gillen; Debbie Gipson; Susan M Hailpern; Yoshio N Hall; Yun Han; Kevin He; William Herman; Michael Heung; Richard A Hirth; David Hutton; Steven J Jacobsen; Yan Jin; Kamyar Kalantar-Zadeh; Alissa Kapke; Csaba P Kovesdy; Danielle Lavallee; Janet Leslie; Keith McCullough; Zubin Modi; Miklos Z Molnar; Maria Montez-Rath; Hamid Moradi; Hal Morgenstern; Purna Mukhopadhyay; Brahmajee Nallamothu; Danh V Nguyen; Keith C Norris; Ann M O'Hare; Yoshitsugu Obi; Christina Park; Jeffrey Pearson; Ronald Pisoni; Praveen K Potukuchi; Panduranga Rao; Kaitlyn Repeck; Connie M Rhee; Jillian Schrager; Douglas E Schaubel; David T Selewski; Sally F Shaw; Jiaxiao M Shi; Monica Shieu; John J Sim; Melissa Soohoo; Diane Steffick; Elani Streja; Keiichi Sumida; Manjula K Tamura; Anca Tilea; Lan Tong; Dongyu Wang; Mia Wang; Kenneth J Woodside; Xin Xin; Maggie Yin; Amy S You; Hui Zhou; Vahakn Shahinian Journal: Am J Kidney Dis Date: 2018-03 Impact factor: 8.860
Authors: Brian Hutton; Georgia Salanti; Deborah M Caldwell; Anna Chaimani; Christopher H Schmid; Chris Cameron; John P A Ioannidis; Sharon Straus; Kristian Thorlund; Jeroen P Jansen; Cynthia Mulrow; Ferrán Catalá-López; Peter C Gøtzsche; Kay Dickersin; Isabelle Boutron; Douglas G Altman; David Moher Journal: Ann Intern Med Date: 2015-06-02 Impact factor: 25.391
Authors: Rebecca M Turner; Jonathan Davey; Mike J Clarke; Simon G Thompson; Julian Pt Higgins Journal: Int J Epidemiol Date: 2012-03-29 Impact factor: 7.196
Authors: Rasheeda K Hall; Sarah Morton; Jonathan Wilson; Patti L Ephraim; L Ebony Boulware; Wendy L St Peter; Cathleen Colón-Emeric; Jane Pendergast; Julia J Scialla Journal: BMC Nephrol Date: 2021-06-19 Impact factor: 2.585