Journal article
Dose doubling, relative potency, and dose equivalence of potassium-sparing diuretics affecting blood pressure and serumpotassium: systematic review and meta-analyses
Journal of hypertension, Vol.34(1), pp.11-19
01/01/2016
DOI: 10.1097/HJH.0000000000000762
PMID: 26556568
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 similar to 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.
Details
- Title: Subtitle
- Dose doubling, relative potency, and dose equivalence of potassium-sparing diuretics affecting blood pressure and serumpotassium: systematic review and meta-analyses
- Creators
- George C. Roush - Rutgers, The State University of New JerseyMichael E. Ernst - Univ Iowa Hosp & Clin, Dept Family Med, Iowa City, IA 52242 USAJohn B. Kostis - Rutgers, The State University of New JerseyShamima Yeasmin - University of Iowa Hospitals and ClinicsDomenic A. Sica - Virginia Commonwealth University
- Resource Type
- Journal article
- Publication Details
- Journal of hypertension, Vol.34(1), pp.11-19
- DOI
- 10.1097/HJH.0000000000000762
- PMID
- 26556568
- NLM abbreviation
- J Hypertens
- ISSN
- 0263-6352
- eISSN
- 1473-5598
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 9
- Language
- English
- Date published
- 01/01/2016
- Academic Unit
- Family and Community Medicine; Pharmacy Practice and Science
- Record Identifier
- 9984297347002771
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