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

Abstract

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.

The use of diuretics in heart failure with congestion — a position statement from the Heart Failure Association of the European Society of Cardiology

“…A meta‐analysis of existing observational data underscores the frequent occurrence of hypokalaemia. In a propensity‐matched analysis of real‐world use of thiazides (combined with lower‐dose loop diuretics) and high‐dose loop diuretics in heart failure patients, thiazides, but not high‐dose loop diuretics, were independent predictors of the occurrence of hyponatraemia and hypokalaemia with an indication towards a higher risk for all‐cause mortality . Given the relative safety of high‐dose loop diuretics in the DOSE‐AHF trial, a preference might be given to initial intensification of the loop diuretic dose before adding a thiazide diuretic .…”

“…In a propensity-matched analysis of real-world use of thiazides (combined with lower-dose loop diuretics) and high-dose loop diuretics in heart failure patients, thiazides, but not high-dose loop diuretics, were independent predictors of the occurrence of hyponatraemia and hypokalaemia with an indication towards a higher risk for all-cause mortality. 103 Given the relative safety of high-dose loop diuretics in the DOSE-AHF trial, a preference might be given to initial intensification of the loop diuretic dose before adding a thiazide diuretic. 42 However, in the CARRESS-HF-trial, the addition of metolazone was an intrinsic part of the stepped pharmacologic algorithm, resulting in the recommendation of thiazides as a second-line agent in the Heart Failure Society of America practical guidelines.…”

Associations of worsening renal function with loop diuretics in patients with heart failure with different ejection fraction categories

“…Furthermore, the high risk of WRF in ADHF patients is associated with several pathophysiological processes, including hemodynamic status, activation of the neurohormonal system, the release of in ammatory cytokines and other drug therapies [18][19][20]. Plasma volume reduction leads to WRF in ADHF patients in whom high loop diuretic dose were administered [21].…”

The year in cardiology 2018: heart failure

“…Diuretics are one of the most valuable and least researched class of agents for heart failure. A recent cohort study suggested that intensification of loop diuretic dose may be a better strategy than using a combination of thiazide and loop diuretics albeit in a patients who probably had low rates of treatment with mineralo-corticoid receptor antagonists (98). Whether furosemide or torasemide is the better diuretic agent is the question posed in the TRANSFORM-HF trial [https://clinicaltrials.gov/ct2/show/NCT03296813].…”