Combination diuretic treatment in severe heart failure: a randomised controlled trial.

Channer, KS; McLean, Kenneth A; Lawson-Matthew, P J; Richardson, Michael R.

doi:10.1136/hrt.71.2.146

Cited by 179 publications

(97 citation statements)

References 9 publications

(5 reference statements)

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“…Physiologically this seems like an attractive approach to decongestion, one that is supported in the current heart failure practice guidelines, despite no randomized trials comparing combination diuretic therapy with a thiazide to loop diuretics alone 4. In fact, most studies examining metolazone use in HF are small, single‐center retrospective analyses without a control arm, published over 25 years ago, that focused on end points like urinary volume and sodium concentration as opposed to clinical outcomes 8, 10, 28, 29. Nevertheless, the cumulative existing evidence in only 350 patients does illustrate that metolazone produces a 3‐fold increase in natriuresis, increases weight loss and improves diuresis in patients who were previously not suitable for hospital discharge 7, 8, 9, 10, 28, 29, 30…”

Section: Discussionmentioning

confidence: 99%

“…Both US and European Heart Failure (HF) guidelines state that when diuresis remains inadequate with loop diuretic therapy, either escalation of loop diuretic dose or the addition of a thiazide diuretic may be considered to intensify the regimen, yet these recommendation are based on limited data to support the relative safety of each appraoch 4, 5, 6. Notably, sequential nephron blockade further limits the ability of the kidney to regulate fluid and electrolyte excretion beyond loop diuretic monotherapy, potentially leading to complications such as hyponatremia, hypokalemia, and worsening renal function (WRF) 7, 8, 9, 10…”

Section: Introductionmentioning

confidence: 99%

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Outcomes Associated With a Strategy of Adjuvant Metolazone or High‐Dose Loop Diuretics in Acute Decompensated Heart Failure: A Propensity Analysis

Brisco‐Bacik

Maaten

Houser

et al. 2018

JAHA

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BackgroundIn acute decompensated heart failure, guidelines recommend increasing loop diuretic dose or adding a thiazide diuretic when diuresis is inadequate. We set out to determine the adverse events associated with a diuretic strategy relying on metolazone or high‐dose loop diuretics.Methods and ResultsPatients admitted to 3 hospitals using a common electronic medical record with a heart failure discharge diagnosis who received intravenous loop diuretics were studied in a propensity‐adjusted analysis of all‐cause mortality. Secondary outcomes included hyponatremia (sodium <135 mEq/L), hypokalemia (potassium <3.5 mEq/L) and worsening renal function (a ≥20% decrease in estimated glomerular filtration rate). Of 13 898 admissions, 1048 (7.5%) used adjuvant metolazone. Metolazone was strongly associated with hyponatremia, hypokalemia, and worsening renal function (P<0.0001 for all) with minimal effect attenuation following covariate and propensity adjustment. Metolazone remained associated with increased mortality after multivariate and propensity adjustment (hazard ratio=1.20, 95% confidence interval 1.04–1.39, P=0.01). High‐dose loop diuretics were associated with hypokalemia and hyponatremia (P<0.002) but only worsening renal function retained significance (P<0.001) after propensity adjustment. High‐dose loop diuretics were not associated with reduced survival after multivariate and propensity adjustment (hazard ratio=0.97 per 100 mg of IV furosemide, 95% confidence interval 0.90–1.06, P=0.52).ConclusionsDuring acute decompensated heart failure, metolazone was independently associated with hypokalemia, hyponatremia, worsening renal function and increased mortality after controlling for the propensity to receive metolazone and baseline characteristics. However, under the same experimental conditions, high‐dose loop diuretics were not associated with hypokalemia, hyponatremia, or reduced survival. The current findings suggest that until randomized control trial data prove otherwise, uptitration of loop diuretics may be a preferred strategy over routine early addition of thiazide type diuretics when diuresis is inadequate.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Outcomes Associated With a Strategy of Adjuvant Metolazone or High‐Dose Loop Diuretics in Acute Decompensated Heart Failure: A Propensity Analysis

Brisco‐Bacik

Maaten

Houser

et al. 2018

JAHA

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“…Sequential strategies have been shown to be successful even in patients with advanced chronic renal failure or heart failure. 7 In crossover studies there appears to be little difference in the response to equipotent doses of different thiazides 8 -personal choice may be the best guide.…”

Section: Cme Renal Medicinementioning

confidence: 99%

Clinical use of diuretics

Plant

2003

Clinical Medicine

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“…Such combinations of diuretics, each acting on different segments of the nephron-known as "sequential nephron blockade"-break the resistance to diuretics in edematous states [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Although this physiologically grounded rationale is more effective than high-dose monotherapy when a rapid and robust diuretic response is needed, such treatment may lead to complications such as fluid and electrolyte disturbances [13,28,29].…”

Section: Introductionmentioning

confidence: 99%

Torasemide significantly reduces thiazide-induced potassium and magnesium loss despite supra-additive natriuresis

Knauf

Mutschler

Velázquez

et al. 2009

Eur J Clin Pharmacol

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Background Resistance to high-dose loop diuretics can be overcome either by co-administration with thiazides or by treatment with medium-dose loop diuretics combined with thiazides. Combination therapy has been proven to be superior to high-dose loop diuretic monotherapy for cardiac and renal edema. However, such a strongly efficacious short-term regimen is often complicated by undesired effects, including circulatory collapse and electrolyte disturbances. The question of whether the loop diuretic/ thiazide combinations are efficacious and safe when conventional doses are combined has not yet been answered. Methods The effects of hydrochlorothiazide (HCT) and torasemide (TO) given alone on the excretion of Na + , Cl -, K + , Mg 2+ , and Ca 2+ were compared with the effects of combined administration of the diuretics in 12 healthy volunteers. Results The co-administration of HCT (25 mg) with TO (5 or 10 mg) strongly increased Na + excretion. However, the combination significantly reduced K + and Mg 2+ excretion. The K + -sparing effect of the HCT/TO combination was shown to be due to a significant reduction in the HCTinduced increase in fractional K + excretion by the loop diuretic. Total excretion of Ca 2+ relative to Na + excretion was less with the HCT/TO combination than with TO given alone. Conclusion The enhancement of desired NaCl excretion by the HCT/TO combination with significant reduction of undesired loss of K + and Mg 2+ meets clinical requirements but has to be validated in long-term clinical trials.

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Combination diuretic treatment in severe heart failure: a randomised controlled trial.

Abstract: Objectives-(a) To test the hypothesis that a fixed 3 day course of the

Cited by 179 publications

References 9 publications

Outcomes Associated With a Strategy of Adjuvant Metolazone or High‐Dose Loop Diuretics in Acute Decompensated Heart Failure: A Propensity Analysis

Outcomes Associated With a Strategy of Adjuvant Metolazone or High‐Dose Loop Diuretics in Acute Decompensated Heart Failure: A Propensity Analysis

Clinical use of diuretics

Torasemide significantly reduces thiazide-induced potassium and magnesium loss despite supra-additive natriuresis

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