The use of thiazide and thiazide‐like diuretics in heart failure with congestion

Abstract

We read with great interest the article of Mullens et al.1 about the practical use of diuretics in patients with acute and chronic heart failure (HF). Surprisingly, there is still little evidence about the use of diuretics in HF and the majority of the recommendations about their use are based on expert opinion. We would like to make some comments about the proposed flowchart, especially regarding the role of thiazide diuretics (TD). We agree to use TD as first-line drugs in combined diuretic treatment when there is resistance to loop diuretics. However, the question is when is the most appropriate time to add a TD? Do we have to wait until loop diuretic doses are maximal (as suggested in the flowchart) or could we start earlier? Our opinion is that early addition of TD can be an effective and faster strategy to improve congestion, especially in loop diuretic non-naïve patients. In our experience, more than half of the patients admitted for decompensated HF are already receiving chronic loop diuretic treatment and up to 21% in doses ≥ 80 mg/day of oral furosemide.2 It is very likely that many of these patients have ‘true’ diuretic resistance because prolonged exposure to loop diuretics causes renal adaptation, with progressive hypertrophy and hyperfunction of the distal nephron, increasing local sodium reabsorption. This effect markedly limits the response to loop diuretics. Physiologically, sequential nephron blockade with the addition of TD can antagonize this renal adaptation to chronic loop diuretic therapy and may improve diuretic resistance due to rebound sodium retention. To increase the loop diuretic dose is the most frequently considered strategy but, for the reasons mentioned above, we believe that early addition of TD should also be considered, especially in loop diuretic non-naïve patients. To prove this hypothesis, we are carrying out a multicentre, double-blind, phase IV clinical trial (CLOROTIC, NCT01647932) to determine whether the addition of a thiazide-type diuretic (hydrochlorothiazide) to an intravenous loop diuretic treatment is superior to placebo in improving congestive symptoms in patients admitted for acute HF. The study design has been described in detail elsewhere.3 At present, the study is in the final phase of recruitment and we hope to communicate the preliminary results by the end of this year.