Exploring safety of down-titrating diuretics in heart failure management

Aims: Loop diuretics are widely used in heart failure (HF) for symptom relief. Guidelines advise treating patients with the lowest possible dose of loop diuretics to maintain euvolaemia, based on expert opinion only. However, data on the safety of this practice are scarce. This analysis aims to investigate the clinical course after changing loop diuretics in stable HF patients. Methods and results: A post-hoc analysis from the TIME-CHF study was conducted in 622 patients. Daily loop diuretic doses were meticulously recorded, resulting in 11 035 dose evaluations assessed. The frequency of relevant events within 30 days (hospitalization, death, dose change) following an up-titration, down-titration, or no change in diuretic therapy was calculated. Risk of hospitalization and deaths 30 days after down-titration was estimated after adjusting for congestion level. At baseline the cohort consisted mostly of males (59%), with a mean age of 77 years. Patients were highly symptomatic with 76% classified as New York Heart Association class III or IV. Within 30 days after a down-titration, diuretic dose necessitated an increase in 30.4% of cases, compared with 20.7% following up-titration and 8.0% on a stable dose. Hospitalization and death were significantly more frequent following down-titration (3.4% and 2% within 30 days, respectively) than with a stable dose (1% and 0.6%, p < 0.001). Similar hospitalization rates were observed after up-titration. The risk of hospitalization doubled and of death tripled after down-titration in patients with similar congestion levels. Conclusions: There is a significant risk that reduction in diuretic dose requires restart or increase of diuretics within a short period. Additionally, there may be a significant risk associated with diuretic dose reduction. Therefore, HF patients need to be closely monitored after down-titration of loop diuretic therapy.