Resistance to Diuretics in Heart Failure: Any Role for Empagliflozin?

Author(s): Niki Katsiki, Filippos Triposkiadis*

Journal Name: Current Vascular Pharmacology

Volume 17 , Issue 4 , 2019

Become EABM
Become Reviewer
Call for Editor

Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: Executive summary: A report of the American college of cardiology foundation/American heart association task force on practice guidelines. Circulation 2013; 128: 1810-52.
Ponikowski P, Voors AA, Anker SD, 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 J Heart Fail 2016; 18: 891-975.
Sarafidis PA, Georgianos PI, Lasaridis AN. Diuretics in clinical practice. Part I: mechanisms of action, pharmacological effects and clinical indications of diuretic compounds. Expert Opin Drug Saf 2010; 9: 243-57.
Papadimitriou L, Hamo CE, Butler J. Heart failure guidelines on pharmacotherapy. Handb Exp Pharmacol 2017; 243: 109-29.
Hoorn EJ, Ellison DH. Diuretic resistance. Am J Kidney Dis 2017; 69: 136-42.
Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999; 341: 709-17.
Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011; 364: 11-21.
Tamargo J, Segura J, Ruilope LM. Diuretics in the treatment of hypertension. Part 2: Loop diuretics and potassium-sparing agents. Expert Opin Pharmacother 2014; 15: 605-21.
Verbrugge FH. Diuretic resistance in acute heart failure. Eur Heart J Acute Cardiovasc Care 2018; 7: 379-89.
De Bruyne LK. Mechanisms and management of diuretic resistance in congestive heart failure. Postgrad Med J 2003; 79: 268-71.
Sica DA. Pharmacotherapy in congestive heart failure: Drug absorption in the management of congestive heart failure: Loop diuretics. Congest Heart Fail 2003; 9: 287-92.
Sica DA, Gehr TWB, Frishman WH. Use of diuretics in the treatment of heart failure in older adults. Heart Fail Clin 2017; 13: 503-12.
Wilcox CS, Mitch WE, Kelly RA, et al. Response of the kidney to furosemide. I. Effects of salt intake and renal compensation. J Lab Clin Med 1983; 102: 450-8.
Stanton BA, Kaissling B. Adaptation of distal tubule and collecting duct to increased Na delivery. II. Na+ and K+ transport. Am J Physiol 1998; 255: 1269-75.
Rao VS, Planavsky N, Hanberg JS, et al. Compensatory distal reabsorption drives diuretic resistance in human heart failure. J Am Soc Nephrol 2017; 28: 3414-24.
Ter Maaten JM, Rao VS, Hanberg JS, et al. Renal tubular resistance is the primary driver for loop diuretic resistance in acute heart failure. Eur J Heart Fail 2017; 19: 1014-22.
Shchekochikhin D, Al Ammary F, Lindenfeld JA, Schrier R. Role of diuretics and ultrafiltration in congestive heart failure. Pharmaceuticals (Basel) 2013; 6: 851-66.
Oh SW, Han SY. Loop diuretics in clinical practice. Electrolyte Blood Press 2015; 13: 17-21.
Qavi AH, Kamal R, Schrier RW. Clinical use of diuretics in heart failure, cirrhosis, and nephrotic syndrome. Int J Nephrol 2015; 2015: 975934.
Packer M. Activation and inhibition of sodium-hydrogen exchanger is a mechanism that links the pathophysiology and treatment of diabetes mellitus with that of heart failure. Circulation 2017; 136: 1548-59.
Ellison DH, Felker GM. Diuretic treatment in heart failure. N Engl J Med 2017; 377: 1964-75.
Thomas MC. Type 2 diabetes and heart failure: Challenges and solutions. Curr Cardiol Rev 2016; 12: 249-55.
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373: 2117-28.
Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 2016; 375: 323-34.
Fitchett D, Zinman B, Wanner C, et al. Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: Results of the EMPA-REG OUTCOME trial. Eur Heart J 2016; 37: 1526-34.
Wanner C, Lachin JM, Inzucchi SE, et al. Empagliflozin and clinical outcomes in patients with type 2 diabetes mellitus, established cardiovascular disease, and chronic kidney disease. Circulation 2018; 137: 119-29.
Weir MR. The kidney and type 2 diabetes mellitus: therapeutic implications of SGLT2 inhibitors. Postgrad Med 2016; 128: 290-8.
Katsiki N, Papanas N, Mikhailidis DP. Dapagliflozin: More than just another oral glucose-lowering agent? Expert Opin Investig Drugs 2010; 19: 1581-9.
Katsiki N, Mikhailidis DP, Theodorakis MJ. Sodium-glucose Cotransporter 2 Inhibitors (SGLT2i): Their role in cardiometabolic risk management. Curr Pharm Des 2017; 23: 1522-32.
Katsiki N, Athyros VG, Mikhailidis DP. Cardiovascular effects of sodium-glucose cotransporter 2 inhibitors: Multiple actions. Curr Med Res Opin 2016; 32: 1513-4.
American Diabetes Association Pharmacologic approaches to glycemic treatment: Standards of medical care in diabetes-2018. Diabetes Care 2018; 41(Suppl. 1): 73-85.
Piepoli MF, Hoes AW, Agewall S, et al. 2016 European guidelines on cardiovascular disease prevention in clinical practice: The sixth joint task force of the European society of cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of 10 societies and by invited experts) developed with the special contribution of the European association for cardiovascular prevention & rehabilitation (EACPR). Eur Heart J 2016; 20161(37): 2315-81.
FDA News Release FDA approves Jardiance to reduce cardiovascular death in adults with type 2 diabetes Available from. Accessed on July 23, 2018.
Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377: 644-57.
Frampton JE. Empagliflozin: A review in type 2 diabetes. Drugs 2018; 78: 1037-48.
Packer M, Anker SD, Butler J, Filippatos G, Zannad F. Effects of sodium-glucose cotransporter 2 inhibitors for the treatment of patients with heart failure: Proposal of a novel mechanism of action. JAMA Cardiol 2017; 2: 1025-9.
Mordi NA, Mordi IR, Singh JS, et al. Renal and cardiovascular effects of sodium-glucose cotransporter 2 (SGLT2) inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure (RECEDE-CHF): Protocol for a randomised controlled double-blind cross-over trial. BMJ Open 2017; 7: e018097.
Tubular Reabsorption Article. Available from on July 23, 2018.
Horita S, Nakamura M, Suzuki M, et al. The role of renal proximal tubule transport in the regulation of blood pressure. Kidney Res Clin Pract 2017; 36: 12-21.
Sairaku A, Nakano Y, Kihara Y. Increased urine output by ipragliflozin in a non-diabetic patient with a diuretic-resistant heart failure. Int J Cardiol 2015; 180: 42-3.
Wilcox CS, Shen W, Boulton DW, Leslie BR, Griffen SC. Interaction between the sodium-glucose-linked transporter 2 inhibitor dapagliflozin and the loop diuretic bumetanide in normal human subjects. J Am Heart Assoc 2018; 7: e007046.
US National Library of Medicine. SGLT2 inhibition in combination with diuretics in heart failure (RECEDE-CHF). Available from ( Accessed on August 31, 2018
US National Library of Medicine. EMPagliflozin outcome trial in patients with chronic heart failure with reduced ejection fraction (EMPEROR-Reduced). Available from Accessed on August 31, 2018.
US National Library of Medicine. EMPagliflozin outcome trial in patients with chronic heart failure with preserved ejection fraction (EMPEROR-Preserved)Available from; Accessed on August 31, 2018..

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 31 August, 2018
Page: [421 - 424]
Pages: 4
DOI: 10.2174/1570161116666180831124717

Article Metrics

PDF: 38