Use of metolazone as an adjunct therapy to loop diuretics in diuretic resistant acute decompensation of heart failure: A systematic review and meta-analysis

Abstract

Introduction: Loop diuretics are the first-line treatment for volume overload in acute decompensation of congestive heart failure (AHF). Loop diuretic resistance is common due to pharmacologic tachyphylaxis. Therefore, thiazide and thiazide-like diuretics are often used as add-on therapy to combine two different pharmacologic mechanisms. This systemic review and meta-analysis aimed to synthesize the current evidence on the efficacy and safety of metolazone and other thiazide-like diuretics in AHF. Methods: PRISMA guidelines were followed in conducting this systematic review. PubMed, Scopus, PubMed Central, and Embase databases were searched using relevant keywords for studies published before 5 Jan 2022. Abstract and title screening was performed, followed by full-text screening using the Covidence software. Data were extracted, and analysis was done using Cochrane Review Manager (RevMan v5.1). The results were reported in odds ratio and mean difference with 95% confidence intervals. Results: Out of 2999 studies identified by database search, eight studies met the inclusion criteria (2 RCTs and 6 cohort studies). Pooled analysis using a random-effects model showed no difference in mean difference among the metolazone group and control group for 24 hours total urine output (MD 69.32, 95% CI -638.29 to 776.94; n = 551; I2 = 84%), change in urine output in 24 hours (MD -284.09, 95% CI -583.99 to 15.81; n = 345; I2 = 0%), 48 hours total urine output (MD -465.62, 95% CI -1302.22 to 370.99; n = 242; I2 = 0%) and urine output at 72 hours (MD -13.24, 95% CI -90.88 to 64.40; n = 205; I2 = 0%). However, studies with furosemide only in the comparator arm, 24 hours of total urine outcome favored metolazone (MD 692.70, 95% CI 386.59 to 998.82; n = 334; I2 = 0%). There was no difference between the two groups in the rate of adverse events, loss of weight, mortality, or readmission rates. Conclusion: Metolazone therapy in diuretic resistant AHF may improves urine output and facilitates achieving a net negative balance. Thus, metolazone and thiazide-like diuretics can be used as add-on therapy in acute decompensation of heart failure, especially in diuretic resistance.