George C Roush1, Michael E Ernst, John B Kostis, Shamima Yeasmin, Domenic A Sica. 1. aUCONN School of Medicine and St. Vincent's Medical Center, Department of Medicine, Bridgeport, Connecticut, bUniversity of Iowa Hospital and Clinics, Department of Family Medicine, Iowa City, Iowa, cCardiovascular Institute, Rutgers-Robert Wood Johnson Medical School, Chairman, Department of Medicine, New Brunswick, New Jersey, dDepartment of Medicine and Pharmacology, Virginia Commonwealth University, Richmond, Virginia, USA.
Abstract
BACKGROUND: Potassium-sparing diuretics (PSDs) are valuable antihypertensives with additional benefits unrelated to control of systolic blood pressure (SBP). However, their key parameters affecting SBP and serum potassium are poorly defined, fostering underutilization. METHOD: Consequently, we conducted systematic reviews and meta-analyses, yielding 3668 articles and ultimately 84 randomized comparisons. RESULTS: For office SBP, overall placebo-adjusted changes were triamterene -1.9 (low dose only), amiloride -9.9, spironolactone -13.2, and eplerenone -9.2. Differences in antihypertensive effect were due to potency rather than efficacy. Doubling amiloride, eplerenone, and spironolactone doses reduced SBP (95% confidence limits) on average by -2.3 (-3.1, -1.5). Relative antihypertensive potencies were spironolactone>amiloride>eplerenone. Spironolactone had significantly greater antihypertensive potency than amiloride, -4.0 (-7.4, -0.6), and eplerenone, -5.5 (-7.4, -3.6). Dose equivalencies were eplerenone-spironolactone 4.5-to-1 (e.g., eplerenone 125∼spironolactone 25), amiloride-spironolactone 3.3-to-1, and eplerenone-amiloride 1.4-to-1. Increases in serum potassium from amiloride and spironolactone at commonly used doses averaged 0.14-0.29 mEq/l; the dose doubling effect was 0.16 (0.10, 0.22). Spironolactone caused greater hyperkalemia than amiloride across their dose ranges: 0.14, P = 0.043. Seven features make important bias unlikely: a comprehensive literature search, adjustment for covariates, all models explaining 95-100% of the between-study variability, similar dose doubling effects among PSDs, two different methods giving the same potency sequence, similar results from double blind comparisons, and similar results for eplerenone versus spironolactone from analysing direct comparison data (i.e., no meta-regression) for office and 24-h SBP. CONCLUSION: This synthesis accomplishes for PSDs what has already been achieved for thiazide-type diuretics and other antihypertensives and can guide the application of these underutilized medicines.
BACKGROUND:Potassium-sparing diuretics (PSDs) are valuable antihypertensives with additional benefits unrelated to control of systolic blood pressure (SBP). However, their key parameters affecting SBP and serum potassium are poorly defined, fostering underutilization. METHOD: Consequently, we conducted systematic reviews and meta-analyses, yielding 3668 articles and ultimately 84 randomized comparisons. RESULTS: For office SBP, overall placebo-adjusted changes were triamterene -1.9 (low dose only), amiloride -9.9, spironolactone -13.2, and eplerenone -9.2. Differences in antihypertensive effect were due to potency rather than efficacy. Doubling amiloride, eplerenone, and spironolactone doses reduced SBP (95% confidence limits) on average by -2.3 (-3.1, -1.5). Relative antihypertensive potencies were spironolactone>amiloride>eplerenone. Spironolactone had significantly greater antihypertensive potency than amiloride, -4.0 (-7.4, -0.6), and eplerenone, -5.5 (-7.4, -3.6). Dose equivalencies were eplerenone-spironolactone 4.5-to-1 (e.g., eplerenone 125∼spironolactone 25), amiloride-spironolactone 3.3-to-1, and eplerenone-amiloride 1.4-to-1. Increases in serum potassium from amiloride and spironolactone at commonly used doses averaged 0.14-0.29 mEq/l; the dose doubling effect was 0.16 (0.10, 0.22). Spironolactone caused greater hyperkalemia than amiloride across their dose ranges: 0.14, P = 0.043. Seven features make important bias unlikely: a comprehensive literature search, adjustment for covariates, all models explaining 95-100% of the between-study variability, similar dose doubling effects among PSDs, two different methods giving the same potency sequence, similar results from double blind comparisons, and similar results for eplerenone versus spironolactone from analysing direct comparison data (i.e., no meta-regression) for office and 24-h SBP. CONCLUSION: This synthesis accomplishes for PSDs what has already been achieved for thiazide-type diuretics and other antihypertensives and can guide the application of these underutilized medicines.
Authors: Tina Sc Tam; May Hy Wu; Sarah C Masson; Matthew P Tsang; Sarah N Stabler; Angus Kinkade; Anthony Tung; Aaron M Tejani Journal: Cochrane Database Syst Rev Date: 2017-02-28
Authors: Mengyun Lu; Li-Yuan Chen; Salina Gairhe; Adrien J Mazer; Stasia A Anderson; Jasmine N H Nelson; Audrey Noguchi; Mohammad Abdul Hai Siddique; Edward J Dougherty; Yvette Zou; Kathryn A Johnston; Zu-Xi Yu; Honghui Wang; Shuibang Wang; Junfeng Sun; Steven B Solomon; Rebecca R Vanderpool; Michael A Solomon; Robert L Danner; Jason M Elinoff Journal: Am J Physiol Lung Cell Mol Physiol Date: 2022-01-19 Impact factor: 5.464
Authors: George C Roush; Ramy Abdelfattah; Steven Song; Michael E Ernst; Domenic A Sica; John B Kostis Journal: J Clin Hypertens (Greenwich) Date: 2018-09-24 Impact factor: 3.738