Short-term diuretic withdrawal in stable outpatients with mild heart failure and no fluid retention receiving optimal therapy: a double-blind, multicentre, randomized trial

Abstract

Aims Although loop diuretics are widely used to treat heart failure (HF), there is scarce contemporary data to guide diuretic adjustments in the outpatient setting. Methods and results In a prospective, randomized and double-blind protocol, we tested the safety and tolerability of withdrawing low-dose furosemide in stable HF outpatients at 11 HF clinics in Brazil. The trial had two blindly adjudicated co-primary outcomes: (i) symptoms assessment quantified as the area under the curve (AUC) of a dyspnoea score on a visual-analogue scale evaluated at 4 time-points (baseline, Day 15, Day 45, and Day 90) and (ii) the proportion of patients maintained without diuretic reuse during follow-up. We enrolled 188 patients (25% females; 59 ± 13 years old; left ventricular ejection fraction = 32 ± 8%) that were randomized to furosemide withdrawal (n = 95) or maintenance (n = 93). For the first co-primary endpoint, no significant difference in patients’ assessment of dyspnoea was observed in the comparison of furosemide withdrawal with continuous administration [median AUC 1875 (interquartile range, IQR 383–3360) and 1541 (IQR 474–3124), respectively; P = 0.94]. For the second co-primary endpoint, 70 patients (75.3%) in the withdrawal group and 77 patients (83.7%) in the maintenance group were free of furosemide reuse during follow-up (odds ratio for additional furosemide use with withdrawal 1.69, 95% confidence interval 0.82–3.49; P = 0.16). Heart failure-related events (hospitalizations, emergency room visits, and deaths) were infrequent and similar between groups (P = 1.0). Conclusions Diuretic withdrawal did not result in neither increased self-perception of dyspnoea nor increased need of furosemide reuse. Diuretic discontinuation may deserve consideration in stable outpatients with no signs of fluid retention receiving optimal medical therapy. ClinicalTrials.gov Identifier NCT02689180.

Management of low blood pressure in ambulatory heart failure with reduced ejection fraction patients

“…Only a few trials have targeted the decrease in diuretics . A controlled randomized trial has recently been reported and confirmed the feasibility of this approach in stable HFrEF patients . Serial monitoring of stable natriuretic peptide concentrations may be useful during diuretic titration to provide reassurance that congestion is not worsening significantly.…”

Diuretikatherapie bei Herzinsuffizienz

“…Ziel ist die niedrigste Dosis zur Erhaltung der Euvolämie. In einer prospektiven brasilianischen Studie bei herzinsuffizienten Patienten mit LV-EF < 45 %, die euvolämisch, asymptomatisch oder wenig symptomatisch waren (NYHA-Stadium I-II), führte das Absetzen der oralen Furosemidtherapie nicht zur Verschlechterung der Dyspnoe oder zu klinischen Komplikationen [31]. Somit gilt insbesondere bei ambulanten Patienten in der Langzeittherapie: "So wenig wie möglich, so viel als nötig".…”

Outcomes of diuretics in rheumatic heart disease with compensated chronic heart failure: a retrospective study

“…7 Two small prospective pilot studies showed that long-term maintenance of lower-dose diuretics for stable CHF patients was feasible and did not worsen the clinical situation. 12 Further, in a prospective, randomized, and double-blind study on the safety and tolerability of withdrawing low-dose furosemide in stable HF outpatients in Brazil, Rohde et al 13 recently found that short-term diuretic withdrawal may be feasible in outpatients with compensated HF after receiving optimal medical therapy. These results suggested that the diuretics use in patients with CHF is dynamic and vary according to the state of congestion, which means that application approaches and dose of diuretics in CHF patients with euvolaemia should be adjusted as early as possible using a careful, de-escalation therapy [defined as intermittent diuretics use (IDU)] after achieving successful decongestion with diuretic therapy.…”

“…Two small prospective pilot studies showed that long‐term maintenance of lower‐dose diuretics for stable CHF patients was feasible and did not worsen the clinical situation 12 . Further, in a prospective, randomized, and double‐blind study on the safety and tolerability of withdrawing low‐dose furosemide in stable HF outpatients in Brazil, Rohde et al 13 . recently found that short‐term diuretic withdrawal may be feasible in outpatients with compensated HF after receiving optimal medical therapy.…”