Dosing of loop diuretics in chronic heart failure: it's time for evidence.

Abstract

In an article recently published in the European Journal of Heart Failure, Damman et al.1 retrospectively investigated the effect of diuretic dose on renal function and clinical outcomes in patients with chronic heart failure (HF). The authors report an association between higher doses of loop diuretics and adverse prognosis, both in terms of cardiovascular mortality and HF-related hospitalizations. Moreover, they report a more rapid decrease of glomerular filtration rate (GFR) with higher doses of diuretics. These results are in accord with findings of previous studies, including one of our own.2 The authors should be commended on their work, as dosing of diuretics in chronic HF patients has historically been arbitrary rather than evidence-based. The authors discuss the meta-analysis of Faris et al.,3 which, contrary to the findings by Damman et al.,1 suggests that withdrawal of loop diuretics may result in exacerbation of symptoms and an increase in event rates. In our opinion, the four studies included in this meta-analysis are not appropriate for deduction of relevant conclusions. One study excluded patients with HF4 and another excluded patients with left-sided HF.5 In the third study,6 HF was the indication for diuretic use in only 40% of participants and exclusion criteria included the combined therapy with beta-blockers and angiotensin-converting enzyme (ACE) inhibitors, furosemide dose >80 mg per day or a history of acute HF. The last study included exclusively elderly patients, only 23.3% of whom had a history of HF.7 Overall, a loop diuretic was administered to less than 50% of patients across all four studies. Importantly, the aforementioned studies were designed to withdraw and not reduce the dose of diuretics; the latter appears to be the most cautious and clinically appropriate approach. Damman et al.1 insightfully discuss the need for trials randomizing euvolaemic patients with chronic HF to withdrawal or dose reduction of diuretics and highlight the paucity of such prospective, randomized studies. We would like to highlight two recent studies that prospectively investigated reduction of loop diuretic dose in patients with stable chronic HF. McKie et al.8 decreased the dose of furosemide by 50% in 32 stable patients with HF with reduced ejection fraction (HFrEF) of whom 19 had a baseline GFR <60 ml/min.1.73m2. The authors reported that dose reduction was safe and was accompanied by a 19% increase in GFR in the low GFR group. A trend towards decreased plasma renin with dose reduction was also noted in both groups. In a study from our group,9 40 patients with stable chronic HFrEF on high baseline furosemide dose (≥120 mg daily) were randomized to receive either their initial dose or one-third of it. Long-term maintenance of decreased dose was feasible in 95% of the participants. The 1- and 2-year survival rates free from HF-related hospitalization or cardiac death were significantly higher in the reduced dose group. Furthermore, the patients in the high diuretic dose group experienced worsening of renal function significantly more often compared with the patients in the reduced dose group. In our opinion, further prospective randomized studies are warranted to determine if systematic reduction of furosemide doses in euvolaemic HF patients can lead to improved clinical outcomes. Chris J. Kapelios 3rd Department of Cardiology University of Athens School of Medicine 67 Mikras Asias Street 11 527 Athens, Greece E-mail: [email protected] Konstantinos Malliaras 3rd Department of Cardiology University of Athens School of Medicine Athens, Greece John N. Nanas 3rd Department of Cardiology University of Athens School of Medicine Athens, Greece