Combination therapy with metolazone and loop diuretics in outpatients with refractory heart failure: an observational study and review of the literature.

Metolazone is a potent thiazide-like diuretic. It is recommended in severe congestive heart failure (HF). We conducted a review of the existing literature and found that the available information on the use of metolazone in HF is based on studies containing less than 250 patients in total. Nevertheless, metolazone is widely used, often in combination with a loop diuretic. Absorption of metolazone seems to be reduced in HF. Metolazone produces a diuretic response despite a low glomerular filtration rate. A wide dose range of metolazone has been investigated (< or =2.5 to 200 mg), leaving no clear dosing recommendation. However, in most studies a low starting dose (< or =5 mg) was used. We further report an observational study on 21 patients with refractory systolic HF from our specialized outpatient HF clinic. The aim was to evaluate the effects of metolazone in combination with a loop diuretic in contemporary HF patients. We registered 42 episodes of treatment with metolazone. The maximal dose of metolazone was 5 mg. NYHA functional class improved. A significant reduction during treatment in weight, blood pressure, plasma-sodium and -potassium was seen whereas plasma-BUN and -creatinine increased significantly. Clinically important hypokalemia (<2.5 mM) or hyponatremia (<125 mM) were observed during 10% of the treatment episodes. The literature review and the observational study support the use of low-dose metolazone (< or =5 mg) on top of oral loop diuretics, as an effective and relatively safe treatment in contemporary outpatients with refractory HF.