Comparison of the effects of combination diuretic therapy with oral hydrochlorothiazide or intravenous chlorothiazide in patients receiving intravenous furosemide therapy for the treatment of heart failure

Abstract

Study objective: To compare the effects of combination diuretic therapy with oral hydrochlorothiazide or intravenous chlorothiazide added to background intravenous loop diuretic therapy among patients hospitalized with heart failure.

Design: Single-center, retrospective review.

Setting: Cardiovascular hospital within a university-affiliated teaching institution.

Patients: Eighty-two patients hospitalized for heart failure between September 1, 2009, and August 31, 2011, who were receiving background intravenous furosemide therapy (total daily dose ≥ 160 mg); of those patients, 28 patients also received oral hydrochlorothiazide (median dose 25 mg [interquartile range 25-50 mg]), and 54 patients also received intravenous chlorothiazide (median dose 500 mg [interquartile range 250-750 mg]).

Measurements and main results: The primary outcome was change in 24-hour urine output. Urine output was recorded from the 24 hours before and after the first administration of either oral hydrochlorothiazide or intravenous chlorothiazide. Baseline characteristics, with the exception of female sex (p=0.01) and home loop diuretic dose (p=0.03), were similar between groups. Twenty-four-hour urine output before administration of the thiazide diuretic was not significantly different between groups. After treatment, 24-hour urine output increased in both groups; however, urine output increased to a lesser extent with oral hydrochlorothiazide (from mean ± SD 2104 ± 830 ml to 3038 ± 917 ml) than with intravenous chlorothiazide (from 2342 ± 978 ml to 4128 ± 1755 ml) (p=0.005). Hypokalemia occurred frequently in both groups: 71.4% and 83.3% in the oral hydrochlorothiazide and intravenous chlorothiazide groups, respectively (p=0.21).

Conclusion: Among hospitalized patients with heart failure receiving intravenous loop diuretics, the addition of either oral hydrochlorothiazide or intravenous chlorothiazide augmented diuresis. Urine output increased to a greater extent with intravenous chlorothiazide compared with oral hydrochlorothiazide. However, given the positive response observed, ease of administration, and lower drug cost, oral hydrochlorothiazide should still be considered as an option for combination diuretic therapy in this patient population.

Keywords: combination therapy; heart failure; thiazide diuretics.