Abstract

Background: Acute decompensated heart failure (ADHF) has several presentations, one of the most common being congestion which is treated by intravenous loop diuretics. However, prolonged use of this therapy may lead to resistance that can be overcome with a sequential nephron blockade by adding a thiazide diuretic. Less is known about the safety of that combination. Research question: Is the combination of a thiazide diuretic and a loop diuretic safe and effective? Goal: To perform a meta-analysis of the association between the combination of loop and thiazide diuretics, their efficacy, and potential adverse effects. Methods: We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials that compared patients with ADHF using only a loop diuretic and patients using a thiazide adjuvant therapy, and reported the outcomes of (1) weight change; (2) hypokalemia (potassium ≤ 3.5 mmol/L or potassium ≤ 3.5 mEq/L); (3) 30-day rehospitalization; and (4) length of stay. Heterogeneity was examined with I2 statistics. A random-effects model was employed. Review manager 5.4 was used for statistical analyses. Results: In 4 studies, among 424 patients with ADHF, 212 (50%) were treated with a combination of loop and thiazide diuretics and 212 (50%) had a loop monotherapy treatment. Overall, individuals receiving the diuretic combination experienced greater weight loss (MD -0.73; 95% CI -1.23, -0.24; p=0.004; Fig. 1A), but had higher incidence of hypokalemia (RR 2.36; 95% CI 1.56, 3.58; p<0.0001; Fig. 1B) compared to those who were not receiving. There was no significant difference between both groups in all-cause 30-day rehospitalization (RR 1.26; 95% CI 0.81, 1.96; p=0.30; Fig. 1C) or length of hospital stay (MD 0.26; 95% CI -1.03, 1.54; p=0.70; Fig. 1D). Conclusions: These findings suggest that the combination of a loop and a thiazide diuretic may lower body weight in patients with ADHF. However, its role in improving clinical outcomes remains unclear.

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