Rational Pharmacotherapy in Cardiology

Advanced search

Current Clinical and Pharmacological Approaches to the Prescription of Loop Diuretics in Patients with Chronic Heart Failure

Full Text:


Heart failure (HF) is a growing public health problem with an estimated prevalence of 38 million patients worldwide. Congestion and formation of edema – are typical symptoms of heart failure. Diuretics are the mainstay of therapy in heart failure and are used to relieve congestion and improve exercise tolerance. Also, the administration of diuretics should be considered to reduce the risk of HF hospitalization. Loop diuretics are used by nearly 80% of all chronic HF patients and remain the drugs of choice. Although diuretics are one of the most prescribed classes of drugs, recommendations for their titration scheme for long-term use have not yet been finalized, nor have there been major prospective randomized controlled studies on the effect of diuretics on morbidity and mortality. A Cochrane meta-analysis has shown that in patients with chronic HF, loop and thiazide diuretics might reduce the risk of death and worsening of HF in comparison to placebo and could lead to improved exercise capacity. Guideline recommends the use lowest possible dose of diuretics due to probable electrolyte disturbances, further neurohormonal activation, accelerated kidney function decline, and symptomatic hypotension. Diuretic resistance is associated with an unfavorable prognosis and an increased risk of readmission. There are significant pharmacokinetic differences between the loop diuretics. Compared with furosemide, torasemide has a high bioavailability irrespective of food intake, and carries a longer half‐life and duration of effect; also, the benefits of torasemide are its additional anti-fibrotic and neurohormonal effects. Optimization of diuretic therapy in patients with HF remains a challenge and requires further research, as well as an individual approach to patients, since there is no convincing evidence base.

About the Authors

N. M. Gafurova
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Nupaysat M. Gafurova – MD, Postgraduate Student, Chair of Clinical Pharmacology and Propaedeutics of Internal Medicine

Trubetskaya ul. 8-2, Moscow, 119991

E. V. Shikh
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Evgenia V. Shikh – MD, PhD, Professor, Head of Chair of Clinical Pharmacology and Propaedeutics of Internal Medicine, Director of Institute of Professional Education

Trubetskaya ul. 8-2, Moscow, 119991

O. D. Ostroumova
I.M. Sechenov First Moscow State Medical University (Sechenov University);
Russian Federation

Olga D. Ostroumova – MD, PhD, Professor, Head of Chair of Therapy and Polymorbid Pathology, Russian Medical Academy of Continuous Professional Education; Professor, Chair of Clinical Pharmacology and Propaedeutics of Internal Medicine, Sechenov University

Trubetskaya ul. 8-2, Moscow, 119991, 

Barrikadnaya ul. 2/1, Moscow, 123995


1. Braunwald E. The war against heart failure: the Lancet lecture. Lancet. 2015; 385(9970):812-24. DOI:10.1016/S0140-6736(14)61889-4.

2. Roger V.L. Epidemiology of heart failure. Circ Res. 2013;113(6):646-59. DOI:10.1161/CIRCRESAHA.113.300268.

3. Fomin I.V. Chronic heart failure in Russian Federation: what do we know and what to do. Russian Journal of Cardiology. 2016;(8):7-13 (In Russ.) DOI:10.15829/1560-4071-2016-8-7-13.

4. Mareev V.Y., Fomin I.V., Ageev F.T., et al. Russian Heart Failure Society, Russian Society of Cardiology. Russian Scientific Medical Society of Internal Medicine Guidelines for Heart failure: chronic (CHF) and acute decompensated (ADHF). Diagnosis, prevention and treatment. Kardiologiia. 2018;58(6S):8- 158 (In Russ.) DOI:10.18087/cardio.2475.

5. Packer M. The Future Treatment of Heart Failure? Eur Heart J. 2018;39(1):5-7. DOI:10.1093/eurheartj/ehx745.

6. Ponikowski P., Voors A.A., Anker S.D., et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37(27):2129-200. DOI:10.1093/eurheartj/ehw128.

7. Faris R., Flather M., Purcell H., et al. Current evidence supporting the role of diuretics in heart failure: a meta-analysis of randomised controlled trials. Int J Cardiol. 2002;82(2):149-58. DOI:10.1016/s0167-5273(01)00600-3.

8. Faris R., Flather M.D, Purcell H., et al. Diuretics for heart failure. Cochrane Database Syst Rev. 2006;25(1):CD003838. DOI:10.1002/14651858.CD003838.pub2.

9. Damman K., Kjekshus J., Wikstrand J., et al. Loop diuretics, renal function and clinical outcome in patients with heart failure and reduced ejection fraction. Eur J Heart Fail. 2016;18(3):328-36. DOI:10.1002/ejhf.462.

10. Mullens W., Damman K., Harjola V.P., et al. The use of diuretics in heart failure with congestion - a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2019;21(2):137-155. DOI:10.1002/ejhf.1369.

11. Ferreira J.P., Girerd N., Bettencourt M.P., et al. Lack of diuretic efficiency (but not low diuresis) early in an acutely decompensated heart failure episode is associated with increased 180-day mortality. Cardiorenal Med. 2017;7(2):137-49. DOI:10.1159/000455903.

12. Testani J.M., Hanberg J.S., Cheng S., et al. Rapid and Highly Accurate Prediction of Poor Loop Diuretic Natriuretic Response in Patients with Heart Failure. Circ Heart Fail. 2016;9(1):e002370. DOI:10.1161/CIRCHEARTFAILURE.115.002370.

13. Brinkley D.M., Burpee L.J., Chaudhry S.P. et al. Spot urine sodium as triage for effective diuretic infusion in an ambulatory heart failure unit. J Card Fail. 2018;24(6):349-54. DOI:10.1016/j.cardfail.2018.01.009.

14. Vasko M.R., Cartwright D.B., Knochel J.P., et al. Furosemide absorption altered in decompensated congestive heart failure. Ann Intern Med. 1985;102(3):314-8. DOI:10.7326/0003-4819-102-3-314.

15. Kaissling B., Stanton B.A. Adaptation of distal tubule and collecting duct to increased sodium delivery. Am J Physiol. 1988;255(6 Pt 2):F1256-68. DOI:10.1152/ajprenal.1988.255.6.F1256.

16. Maaten J.M., Dunning A.M., Valente M.A., et al. Diuretic response in acute heart failure - an analysis from ASCEND-HF. Am Heart J. 2015;170(2):313-21. DOI:10.1016/j.ahj.2015.05.003.

17. Huerta C., Varas-Lorenzo C., Castellsague J., Garcia Rodriguez L.A. Non-steroidal anti-inflammatory drugs and risk of first hospital admission for heart failure in the general population. Heart. 2006;92(11):1610-5. DOI:10.1136/hrt.2005.082388.

18. Galve E., Mallol A., Catalan R. et al. Clinical and neurohumoral consequences of diuretic withdrawal in patients with chronic, stabilized heart failure and systolic dysfunction. Eur J Heart Fail. 2005;7(5):892-8. DOI:10.1016/j.ejheart.2004.09.006.

19. Neuberg G.W., Miller A.B., O’Connor C.M., et al. Diuretic resistance predicts mortality in patients with advanced heart failure. Am Heart J. 2002;144(1):31-8. DOI:10.1067/mhj.2002.123144.

20. Greene S.J., Mentz R.J. Potential advantages of torsemide in patients with heart failure: more than just a “water pill”? Eur J Heart Fail. 2018;20(3):471-473. DOI:10.1002/ejhf.1024.

21. Wilcox C.S. New insights into diuretic use in patients with chronic renal disease. J Am Soc Nephrol. 2002;13(3):798-805.

22. Felker G.M., Mentz R.J. Diuretics and ultrafiltration in acute decompensated heart failure. J Am Coll Cardiol. 2012;59(24):2145-53. DOI:10.1016/j.jacc.2011.10.910.

23. Bard R.L., Bleske B.E., Nicklas J.M. Food: an unrecognized source of loop diuretic resistance. Pharmacotherapy. 2004;24(5):630-7. DOI:10.1592/phco.24.6.630.34736.

24. Vargo D.L., Kramer W.G., Black P.K., et al. Bioavailability, pharmacokinetics, and pharmacodynamics of torsemide and furosemide in patients with congestive heart failure. Clin Pharmacol Ther. 1995;57(6):601-9. DOI:10.1016/0009-9236(95)90222-8.

25. Brater D.C. Pharmacokinetics of loop diuretics in congestive heart failure. Br Heart J. 1994;72(2 Suppl):S40-3. DOI: 10.1136/hrt.72.2_suppl.s40.

26. Pham D., Grodin J.L. Dilemmas in the Dosing of Heart Failure Drugs: Titrating Diuretics in Chronic Heart Failure. Card Fail Rev. 2017;3(2):108-12. DOI:10.15420/cfr.2017:10:1.

27. Barroso M.B., Alonso R.M., Jimenez R.M. Simultaneous determination of torasemide and its major metabolite M5 in human urine by high-performance liquid chromatography-electrochemical detection. J Chromatogr Sci. 2001;39(11):491-6. DOI:10.1093/chromsci/39.11.491.

28. Knauf H., Mutschler E. Clinical pharmacokinetics and pharmacodynamics of torasemide. Clin Pharmacokinet. 1998;34(1):1-24. DOI:10.2165/00003088-199834010-00001.

29. Neugebauer G., Besenfelder E., von Möllendorff E. Pharmacokinetics and metabolism of torasemide in man. Arzneimittelforschung. 1988;38(1A):164-6.

30. Schwartz S., Brater D.C., Pound D., et al. Bioavailability, pharmacokinetics, and pharmacodynamics of torsemide in patients with cirrhosis. Clin Pharmacol Ther. 1993;54(1):90-7. DOI:10.1038/clpt.1993.116.

31. Buggey J., Mentz R.J., Pitt B., et al. A reappraisal of loop diuretic choice in heart failure patients. Am Heart J. 2015;169(3):323-33. DOI:10.1016/j.ahj.2014.12.009.

32. Kasama S., Toyama T., Hatori T., et al. Effects of torasemide on cardiac sympathetic nerve activity and left ventricular remodelling in patients with congestive heart failure. Heart. 2006;92(10):1434-40. DOI:10.1136/hrt.2005.079764.

33. Müller K., Gamba G., Jaquet F., Hess B. Torasemide vs. furosemide in primary care patients with chronic heart failure NYHA II to IV-efficacy and quality of life. Eur J Heart Fail. 2003;5(6):793-801. DOI:10.1016/s1388-9842(03)00150-8.

34. Stroupe K.T., Forthofer M.M., Brater D.C., Murray M.D. Healthcare Costs of Patients with Heart Failure Treated with Torasemide or Furosemide. Pharmacoeconomics. 2000;17(5):429-40. DOI:10.2165/00019053-200017050-00002.

35. Miles J.A., Hanumanthu B.K., Patel K., et al. Torsemide versus furosemide and intermediate-term outcomes in patients with heart failure: an updated meta-analysis. J Cardiovasc Med (Hagerstown). 2019;20(6):379-388. DOI:10.2459/JCM.0000000000000794.

36. Instructions for the medical use of the drug Diuver [cited by Feb 02, 2020]. Available from: (In Russ.)


For citations:

Gafurova N.M., Shikh E.V., Ostroumova O.D. Current Clinical and Pharmacological Approaches to the Prescription of Loop Diuretics in Patients with Chronic Heart Failure. Rational Pharmacotherapy in Cardiology. 2020;16(4):595-600. (In Russ.)

Views: 545

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)