Sex differences in the efficacy of diuretics in the treatment of hypertension; a systematic review and meta-analysis
Main Article Content
Abstract
Background: Pharmacological treatment of high blood pressure is considered essential in the prevention of cardiovascular morbidity and mortality, but sex differences may disturb effectiveness. The aim of this systematic review and metaanalysis was to evaluate possible differences in effects for diuretics on blood pressure, heart rate and cardiac function in female compared to male hypertensive individuals.
Methods: We performed a systematic review and meta-analysis on studies on diuretics from 1945 to May 2020. Studies had to present both baseline and follow-up measurements of the interested outcome variables and present data sex-stratified. Mean differences were calculated using a random-effects model.
Results: Eighteen studies investigating diuretics were used in this review. The effect of diuretics on blood pressure was clinically significant in both females and males and more profound in chronic treatment. Heart rate and left ventricular ejection fraction did not change significantly throughout treatment in both sexes, but cardiac output decreased significantly in females. Changes in left ventricular mass were only significant in males.
Conclusion: Diuretics decreased blood pressure in both sexes, especially when used chronically. Nonetheless, sex depending differences on blood pressure, cardiac output and left ventricular mass may suggest diversity in response to diuretics, implying the importance of considering sex-specific treatment strategies.
Keywords:
hypertension, cardiovascular disease, diuretics, sex differences, systematic review, meta-analysis
Article Details
How to Cite
VAES, Esmée W. P. et al.
Sex differences in the efficacy of diuretics in the treatment of hypertension; a systematic review and meta-analysis.
Medical Research Archives, [S.l.], v. 11, n. 11, jan. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4269>. Date accessed: 22 dec. 2024.
doi: https://doi.org/10.18103/mra.v11i11.4269.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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27. Drayer JI, Weber MA, Gardin JM, Lipson JL. Effect of long-term antihypertensive therapy on cardiac anatomy in patients with essential hypertension. Am J Med. Sep 26 1983;75(3a):116-20. doi:10.1016/0002-9343 (83)90128-6
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31. Ferrara LA, de Simone G, Pasanisi F, Mancini M, Mancini M. Left ventricular mass reduction during salt depletion in arterial hypertension. Hypertension. Sep-Oct 1984;6 (5):755-9. doi:10.1161/01.hyp.6.5.755
32. Zamboli P, De Nicola L, Minutolo R, et al. Effect of furosemide on left ventricular mass in non-dialysis chronic kidney disease patients: a randomized controlled trial. Nephrol Dial Transplant. May 2011;26(5):1575-83. doi:10. 1093/ndt/gfq565
33. Lax D, Eicher M, Goldberg SJ. Mild dehydration induces echocardiographic signs of mitral valve prolapse in healthy females with prior normal cardiac findings. Am Heart J. Dec 1992;124(6):1533-40. doi:10.1016/000 2-8703(92)90068-7
34. Verma SP, Silke B, Hussain M, et al. First-line treatment of left ventricular failure complicating acute myocardial infarction: a randomised evaluation of immediate effects of diuretic, venodilator, arteriodilator, and positive inotropic drugs on left ventricular function. J Cardiovasc Pharmacol. Jul 1987;10 (1):38-46. doi:10.1097/00005344-198707000-00006
35. Valette H, Hebert JL, Raffestin B, Lockhart A, Apoil E. Comparison of hemodynamic effects of furosemide and piretanide in normovolemic patients. J Cardiovasc Pharmacol. 1980;2(2):103-11. doi:10.1097/00 005344-198003000-00002
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37. Trippel TD, Van Linthout S, Westermann D, et al. Investigating a biomarker-driven approach to target collagen turnover in diabetic heart failure with preserved ejection fraction patients. Effect of torasemide versus furosemide on serum C-terminal propeptide of procollagen type I (DROP-PIP trial). Eur J Heart Fail. Mar 2018;20(3):460-470. doi:10.1 002/ejhf.960
38. Kurrelmeyer KM, Ashton Y, Xu J, Nagueh SF, Torre-Amione G, Deswal A. Effects of spironolactone treatment in elderly women with heart failure and preserved left ventricular ejection fraction. J Card Fail. Aug 2014;20(8):560-8. doi:10.1016/j.cardfail.2014.05.010
39. Harris SK, Petrella RJ, Overend TJ, Paterson DH, Cunningham DA. Short-term training effects on left ventricular diastolic function and oxygen uptake in older and younger men. Clin J Sport Med. Jul 2003;13(4):245-51. doi:10.1097/00042752-20 0307000-00009
40. Musini VM, Nazer M, Bassett K, Wright JM. Blood pressure‐lowering efficacy of monotherapy with thiazide diuretics for primary hypertension. Cochrane Database of Systematic Reviews. 2014;(5)
41. Puschett J. The hemodynamic effects of diuretics. Nefrologia. 1990;X(1)
42. Ray EC, Boyd-Shiwarski CR, Kleyman TR. Why Diuretics Fail Failing Hearts. Journal of the American Society of Nephrology. 2017;2 8(11):3137-3138. doi:10.1681/asn.2017070797
43. Klungel OH, de Boer A, Paes AH, Seidell JC, Bakker A. Sex differences in the pharmacological treatment of hypertension: a review of population-based studies. J Hypertens. Jun 1997;15(6):591-600. doi:10.10 97/00004872-199715060-00004
44. Thoenes M, Neuberger H, Volpe M, Khan B, Kirch W, Böhm M. Antihypertensive drug therapy and blood pressure control in men and women: an international perspective. Journal of human hypertension. 2010;24(5):3 36-344.
45. Schwartz GL, Turner ST, Chapman AB, Boerwinkle E. Interacting effects of gender and genotype on blood pressure response to hydrochlorothiazide. Kidney international. 2002;62(5):1718-1723.
46. Werner D, Werner U, Meybaum A, et al. Determinants of steady-state torasemide pharmacokinetics: impact of pharmacogenetic factors, gender and angiotensin II receptor blockers. Clin Pharmacokinet. 2008;47(5):323-32. doi:10.21 65/00003088-200847050-00003
47. Werner U, Werner D, Heinbüchner S, et al. Gender is an important determinant of the disposition of the loop diuretic torasemide. J Clin Pharmacol. Feb 2010;50(2):160-8. doi:10. 1177/0091270009337514
48. Cerrutti JA, Quaglia NB, Brandoni A, Torres AM. Effects of gender on the pharmacokinetics of drugs secreted by the renal organic anions transport systems in the rat. Pharmacol Res. Feb 2002;45(2):107-12. doi:10.1006/phrs.2001.0912
49. Sex and Gender Differences in Pharmacology. 1 ed. Handbook of Experimental Pharmacology. Springer Berlin, Heidelberg; 602.
50. Chen Z, Vaughn DA, Fanestil DD. Influence of gender on renal thiazide diuretic receptor density and response. Journal of the American Society of Nephrology. 1994;5(4):1 112-1119. doi:10.1681/asn.V541112
51. Mohseni-Alsalhi Z, Vesseur MAM, Wilmes N, et al. The Representation of Females in Studies on Antihypertensive Medication over the Years: A Scoping Review. Biomedicines. May 12 2023;11(5)doi:10.3390/biomedicines11051435
52. Wilmes N, van Luik EM, Vaes EWP, et al. Exploring Sex Differences of Beta-Blockers in the Treatment of Hypertension: A Systematic Review and Meta-Analysis. Biomedicines. May 22 2023;11(5)doi:10.3390/biomedicines11051494
53. van Luik EM, Vaes EWP, Vesseur MAM, et al. Sex Differences in the Anti-Hypertensive Effect of Calcium-Channel Blockers: A Systematic Review and Meta-Analysis. Biomedicines. Jun 2 2023;11(6)doi:10.3390/biomedicines11061622
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3. MayoClinic. Heart disease in women: Understand symptoms and risk factors. Webpage. 20 September, 2020. Updated 4 October 2019. https://www.mayoclinic.org/diseases-conditions/heart-disease/in-depth/heart-disease/art-20046167
4. Appelman Y, van Rijn BB, ten Haaf ME, Boersma E, Peters SAE. Sex differences in cardiovascular risk factors and disease prevention. Atherosclerosis. 2015/07/01/ 2015;241(1):211-218. doi:https://doi.org/10.1016/j.atherosclerosis.2015.01.027
5. Gao Z, Chen Z, Sun A, Deng X. Gender differences in cardiovascular disease. Medicine in Novel Technology and Devices. 2019/12/0 1/ 2019;4:100025. doi:https://doi.org/10.1016/j.medntd.2019.100025
6. Saklayen MG, Deshpande NV. Timeline of History of Hypertension Treatment. Front Cardiovasc Med. 2016;3:3. doi:10.3389/fcvm. 2016.00003
7. Klabunde R. Cardiovascular physiology concepts. Lippincott Williams & Wilkins; 2011.
8. Kompas F. Diuretica. Web page. 1 December, 2020. Accessed 30 January, 2013. https://nvkfb.nl/wp-content/uploads/2019/03/FK-Inleidende-tekst-Diuretica.pdf
9. Ernst ME, Mann SJ. Diuretics in the treatment of hypertension. Semin Nephrol. Nov 2011;31(6):495-502. doi:10.1016/j.semnephrol.2011.09.004
10. Franson KL, Kuk JM, Lam NP, Lau AH. Gender effect on diuretic response to hydrochlorothiazide and furosemide. Int J Clin Pharmacol Ther. Mar 1996;34(3):101-5.
11. Tamargo J, Rosano G, Walther T, et al. Gender differences in the effects of cardiovascular drugs. Eur Heart J Cardiovasc Pharmacother. Jul 1 2017;3(3):163-182. doi:10.1093/ehjcvp/pvw042
12. Hendriksen LC, van der Linden PD, Lagro-Janssen ALM, et al. Sex differences associated with adverse drug reactions resulting in hospital admissions. Biol Sex Differ. May 3 2021;12(1) :34. doi:10.1186/s13293-021-00377-0
13. Brandoni A, Villar SR, Torres AM. Gender-related differences in the pharmacodynamics of furosemide in rats. Pharmacology. Feb 2004;70(2):107-12. doi:10.1159/000074675
14. Chen JM, Heran BS, Wright JM. Blood pressure lowering efficacy of diuretics as second-line therapy for primary hypertension. Cochrane Database Syst Rev. Oct 7 2009;(4):Cd007187. doi:10.1002/14651858.CD007187.pub2
15. Musini VM, Nazer M, Bassett K, Wright JM. Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension. Cochrane Database Syst Rev. May 29 2014;(5):Cd003824. doi:10.1 002/14651858.CD003824.pub2
16. RoB 2: A revised Cochrane risk-of-bias tool for randomized trials. Webpage. Cochrane Methods Bias. 16 December, 2020. https://methods.cochrane.org/bias/resources/rob-2-revised-cochrane-risk-bias-tool-randomized-trials
17. Higgins JT, J. Cochrane Handbook for Systematic Reviews of Interventions. 2020:chap 6.
18. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. Sep 1986;7(3) :177-88. doi:10.1016/0197-2456(86)90046-2
19. Deeks JJ, Higgins JPT, DG. A. Chapter 10: Analysing data and untertaking meta-analyses. In: Higgins JPT, Thomas J, Chandler J, et al, eds. Cochrane Handbook for Systematic Reviews of Interventions. Cochrane; 2020:chap Chapter 10.
20. Schwarzer G. meta: An R package for meta-analysis. R news. 2007;7(3):40-45.
21. Team RC. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing. Vienna, 2016;
22. Dorsch MP, Gillespie BW, Erickson SR, Bleske BE, Weder AB. Chlorthalidone reduces cardiovascular events compared with hydrochlorothiazide: a retrospective cohort analysis. Hypertension. Apr 2011;57(4):689-94. doi:10.1161/hypertensionaha.110.161505
23. Okada Y, Shibata S, Fujimoto N, Best SA, Levine BD, Fu Q. Long-term effects of a renin inhibitor versus a thiazide diuretic on arterial stiffness and left ventricular diastolic function in elderly hypertensive patients. Am J Physiol Regul Integr Comp Physiol. Oct 1 2017;3 13(4):R400-r409. doi:10.1152/ajpregu.00125.2017
24. Spoelstra-de Man AM, van Ittersum FJ, Schram MT, et al. Aggressive antihypertensive strategies based on hydrochlorothiazide, candesartan or lisinopril decrease left ventricular mass and improve arterial compliance in patients with type II diabetes mellitus and hypertension. J Hum Hypertens. Aug 2006;20(8):599-611. doi:10.1038/sj.jhh.1002025
25. Gottdiener JS, Reda DJ, Williams DW, Materson BJ, Cushman W, Anderson RJ. Effect of single-drug therapy on reduction of left atrial size in mild to moderate hypertension: comparison of six antihypertensive agents. Circulation. Jul 14 1998;98(2):140-8. doi:10.1161/01.cir.98.2.140
26. Giles TD, Sander GE, Roffidal LC, Thomas MG, Given MB, Quiroz AC. Comparison of nitrendipine and hydrochlorothiazide for systemic hypertension. Am J Cardiol. Jul 1 1987;60(1):103-6. doi:10.1016/0002-9149(87)90994-5
27. Drayer JI, Weber MA, Gardin JM, Lipson JL. Effect of long-term antihypertensive therapy on cardiac anatomy in patients with essential hypertension. Am J Med. Sep 26 1983;75(3a):116-20. doi:10.1016/0002-9343 (83)90128-6
28. Drayer JI, Gardin JM, Weber MA, Aronow WS. Changes in ventricular septal thickness during diuretic therapy. Clin Pharmacol Ther. Sep 1982;32(3):283-8. doi:10.1038/clpt.1982.161
29. Materson BJ, Michael UF, Oster JR, Perez-Stable EC. Antihypertensive effects of oxprenolol and propranolol. Clin Pharmacol Ther. Aug 1976;20(2):142-51. doi:10.1002/cpt 1976202142
30. Solini A, Seghieri M, Giannini L, et al. The Effects of Dapagliflozin on Systemic and Renal Vascular Function Display an Epigenetic Signature. J Clin Endocrinol Metab. Oct 1 2019;104(10):4253-4263. doi:10.1210/jc.2019-00706
31. Ferrara LA, de Simone G, Pasanisi F, Mancini M, Mancini M. Left ventricular mass reduction during salt depletion in arterial hypertension. Hypertension. Sep-Oct 1984;6 (5):755-9. doi:10.1161/01.hyp.6.5.755
32. Zamboli P, De Nicola L, Minutolo R, et al. Effect of furosemide on left ventricular mass in non-dialysis chronic kidney disease patients: a randomized controlled trial. Nephrol Dial Transplant. May 2011;26(5):1575-83. doi:10. 1093/ndt/gfq565
33. Lax D, Eicher M, Goldberg SJ. Mild dehydration induces echocardiographic signs of mitral valve prolapse in healthy females with prior normal cardiac findings. Am Heart J. Dec 1992;124(6):1533-40. doi:10.1016/000 2-8703(92)90068-7
34. Verma SP, Silke B, Hussain M, et al. First-line treatment of left ventricular failure complicating acute myocardial infarction: a randomised evaluation of immediate effects of diuretic, venodilator, arteriodilator, and positive inotropic drugs on left ventricular function. J Cardiovasc Pharmacol. Jul 1987;10 (1):38-46. doi:10.1097/00005344-198707000-00006
35. Valette H, Hebert JL, Raffestin B, Lockhart A, Apoil E. Comparison of hemodynamic effects of furosemide and piretanide in normovolemic patients. J Cardiovasc Pharmacol. 1980;2(2):103-11. doi:10.1097/00 005344-198003000-00002
36. Goldsmith SR, Gilbertson DT, Mackedanz SA, Swan SK. Renal effects of conivaptan, furosemide, and the combination in patients with chronic heart failure. J Card Fail. Dec 2011;17(12):982-9. doi:10.1016/j.cardfail.2011.08.012
37. Trippel TD, Van Linthout S, Westermann D, et al. Investigating a biomarker-driven approach to target collagen turnover in diabetic heart failure with preserved ejection fraction patients. Effect of torasemide versus furosemide on serum C-terminal propeptide of procollagen type I (DROP-PIP trial). Eur J Heart Fail. Mar 2018;20(3):460-470. doi:10.1 002/ejhf.960
38. Kurrelmeyer KM, Ashton Y, Xu J, Nagueh SF, Torre-Amione G, Deswal A. Effects of spironolactone treatment in elderly women with heart failure and preserved left ventricular ejection fraction. J Card Fail. Aug 2014;20(8):560-8. doi:10.1016/j.cardfail.2014.05.010
39. Harris SK, Petrella RJ, Overend TJ, Paterson DH, Cunningham DA. Short-term training effects on left ventricular diastolic function and oxygen uptake in older and younger men. Clin J Sport Med. Jul 2003;13(4):245-51. doi:10.1097/00042752-20 0307000-00009
40. Musini VM, Nazer M, Bassett K, Wright JM. Blood pressure‐lowering efficacy of monotherapy with thiazide diuretics for primary hypertension. Cochrane Database of Systematic Reviews. 2014;(5)
41. Puschett J. The hemodynamic effects of diuretics. Nefrologia. 1990;X(1)
42. Ray EC, Boyd-Shiwarski CR, Kleyman TR. Why Diuretics Fail Failing Hearts. Journal of the American Society of Nephrology. 2017;2 8(11):3137-3138. doi:10.1681/asn.2017070797
43. Klungel OH, de Boer A, Paes AH, Seidell JC, Bakker A. Sex differences in the pharmacological treatment of hypertension: a review of population-based studies. J Hypertens. Jun 1997;15(6):591-600. doi:10.10 97/00004872-199715060-00004
44. Thoenes M, Neuberger H, Volpe M, Khan B, Kirch W, Böhm M. Antihypertensive drug therapy and blood pressure control in men and women: an international perspective. Journal of human hypertension. 2010;24(5):3 36-344.
45. Schwartz GL, Turner ST, Chapman AB, Boerwinkle E. Interacting effects of gender and genotype on blood pressure response to hydrochlorothiazide. Kidney international. 2002;62(5):1718-1723.
46. Werner D, Werner U, Meybaum A, et al. Determinants of steady-state torasemide pharmacokinetics: impact of pharmacogenetic factors, gender and angiotensin II receptor blockers. Clin Pharmacokinet. 2008;47(5):323-32. doi:10.21 65/00003088-200847050-00003
47. Werner U, Werner D, Heinbüchner S, et al. Gender is an important determinant of the disposition of the loop diuretic torasemide. J Clin Pharmacol. Feb 2010;50(2):160-8. doi:10. 1177/0091270009337514
48. Cerrutti JA, Quaglia NB, Brandoni A, Torres AM. Effects of gender on the pharmacokinetics of drugs secreted by the renal organic anions transport systems in the rat. Pharmacol Res. Feb 2002;45(2):107-12. doi:10.1006/phrs.2001.0912
49. Sex and Gender Differences in Pharmacology. 1 ed. Handbook of Experimental Pharmacology. Springer Berlin, Heidelberg; 602.
50. Chen Z, Vaughn DA, Fanestil DD. Influence of gender on renal thiazide diuretic receptor density and response. Journal of the American Society of Nephrology. 1994;5(4):1 112-1119. doi:10.1681/asn.V541112
51. Mohseni-Alsalhi Z, Vesseur MAM, Wilmes N, et al. The Representation of Females in Studies on Antihypertensive Medication over the Years: A Scoping Review. Biomedicines. May 12 2023;11(5)doi:10.3390/biomedicines11051435
52. Wilmes N, van Luik EM, Vaes EWP, et al. Exploring Sex Differences of Beta-Blockers in the Treatment of Hypertension: A Systematic Review and Meta-Analysis. Biomedicines. May 22 2023;11(5)doi:10.3390/biomedicines11051494
53. van Luik EM, Vaes EWP, Vesseur MAM, et al. Sex Differences in the Anti-Hypertensive Effect of Calcium-Channel Blockers: A Systematic Review and Meta-Analysis. Biomedicines. Jun 2 2023;11(6)doi:10.3390/biomedicines11061622
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