Diuretic Treatment in Patients with Heart Failure: Current Evidence and Future Directions - Part I: Loop Diuretics

Abstract

Purpose of review: Fluid retention or congestion is a major cause of symptoms, poor quality of life, and adverse outcome in patients with heart failure (HF). Despite advances in disease-modifying therapy, the mainstay of treatment for congestion-loop diuretics-has remained largely unchanged for 50 years. In these two articles (part I: loop diuretics and part II: combination therapy), we will review the history of diuretic treatment and the current trial evidence for different diuretic strategies and explore potential future directions of research.

Recent findings: We will assess recent trials including DOSE, TRANSFORM, ADVOR, CLOROTIC, OSPREY-AHF, and PUSH-AHF amongst others, and assess how these may influence current practice and future research. There are few data on which to base diuretic therapy in clinical practice. The most robust evidence is for high dose loop diuretic treatment over low-dose treatment for patients admitted to hospital with HF, yet this is not reflected in guidelines. There is an urgent need for more and better research on different diuretic strategies in patients with HF.

Keywords: Combination therapy; Decompensated HF; Diuretic treatment; Loop diuretic.

Fig. 1

Mechanism of action of loop diuretics. Abbreviations OAT, organic anion transporter; MRAP, multidrug resistance-associated protein

Fig. 2

Loop diuretic efficacy in recent diuretic trials. Daily furosemide equivalents reported in text in DOSE, ADVOR, and TACTICS trials and estimated from reported cumulative dose in CLOROTIC, EMPA-RESPONSE-AHF, EMPAG-HF, PUSH-AHF, and OSPREY. Daily urine output reported in PUSH-AHF, CLOROTIC, and EMPA-RESPONSE-AHF trials; estimated from reported cumulative urine output at 72 h in the DOSE and TACTICS trials and at 96 h in the OSPREY trial; estimated from figures in the ADVOR and EMPAG trials

Fig. 3

Seventy-two-hour urine output in diuretic trials. Daily furosemide equivalents reported in text in the DOSE, ADVOR, and TACTICS trials and estimated from reported cumulative dose in the CLOROTIC, EMPA-RESPONSE-AHF, EMPAG-HF, PUSH-AHF, and OSPREY trials. Seventy-two-hour urine output reported in the DOSE and TACTICS trials; estimated from urine output reported at 24 h in the PUSH-AHF, CLOROTIC, and EMPA-RESPONSE-AHF trials, at 48 h in the ADVOR trial, and at 96 h in the OSPREY trial; estimated from figures in the EMPAG trial