Spironolactone 50mg / Furosemide 20mg capsules

AimsSeveral diuretic strategies, including furosemide i.v. boluses (FB) or continuous infusion (FC), are used in acute heart failure (AHF).Methods and resultsWe systematically searched phase 3 randomized clinical trials (RCTs) evaluating diuretic regimens in admitted AHF patients within 48 h and irrespective of clinical stabilization. We calculated the odds ratio (OR) of FC or FB plus another diuretic (sequential nephron blockade, SNB) compared to FB alone on 24 h weight loss (WL) and worsening renal function (WRF), with a random-effects model with inverse variance weighting. Urine output, hypokalaemia, hyponatremia, and all-cause mortality/rehospitalization were secondary endpoints. In 25 selected RCTs (7149 patients, mean age 68.9 ± 8.7 years, mean left ventricular ejection fraction 38.2 ± 10.7%), FC [OR 1.55 (95% confidence interval 1.39-1.63)], FB plus tolvaptan [OR 1.57 (1.39-1.77)], FB plus SGLT2i [OR 1.23 (1.06-1.42)], and FB plus thiazide [OR 1.63 (1.37-1.94)] were associated with greater WL than FB. FB plus SGLT2i [OR 1.52 (1.19-1.94)] and FB plus acetazolamide [OR 1.81 (1.31-2.49)] were associated with WRF. FB plus thiazide was associated with both WRF [OR 1.78 (1.43-2.21)] and hypokalaemia [OR 1.69 (1.32-2.16)]. Results were consistent in sensitivity analyses considering urine output, RCTs protocol-established furosemide doses, or daily furosemide dose. Congestion/decongestion scores and clinical outcomes were reported in around 50% of RCTs. In an underpowered exploratory analysis, mortality/rehospitalization was non-significantly lower with SGLT2i [OR 0.45 (0.19-1.07)].ConclusionFC and SNB improve surrogates of response to FB in AHF. SNB is also connoted by WRF and may induce hypokalaemia. The endpoints of diuretic RCTs should be revised and harmonized.

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IntroductionLoop diuretics are a cornerstone in the symptomatic management of heart failure. There is conflicting evidence regarding potential differences between torsemide and furosemide in their effects on heart failure outcomes. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) to compare the therapeutic efficacy of furosemide versus torsemide in the management of heart failure.MethodsMedline/PubMed, Embase, and Cochrane Central Register of Controlled Trials were queried for studies comparing furosemide to torsemide in heart failure from inception to January 2023. Outcomes of interest included all-cause mortality, hospitalization due to heart failure, and weight change.ResultsOur analysis included 10 RCTs comprising 4011 patients, of whom 2019 were treated with furosemide and 1992 patients were treated with torsemide. There was no significant difference between the groups in terms of all-cause mortality (OR = 0.99; 95% CI: 0.97-1.02; p = 0.66; I 2 = 0.03%) or heart failure hospitalization (OR = 0.96; 95% CI: 0.87-1.06; p = 0.38; I 2 = 89%). Both diuretics had a significant effect on weight change: torsemide (mean difference 2.36; 95% CI: 0.5-4.22; p = 0.01; I 2 = 0.0%) and furosemide (mean difference 2.48; 95% CI: 0.81-4.15; p = 0.00; I 2 = 0.0%). There was no significant difference in weight change between the two diuretics (mean difference -0.15; 95% CI: -0.82-0.52; p = 0.66; I 2 = 94%).ConclusionsFurosemide and torsemide have similar impacts on mortality, hospitalization due to heart failure, and weight change in patients with congestive heart failure.

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BackgroundFluid overload is common in critically ill patients and is associated with worse outcomes. Diuretics are the mainstay of active fluid removal in patients with preserved renal function. The optimal diuretic strategy for fluid removal remains uncertain.MethodsWe conducted a systematic review and Bayesian random-effects network meta-analysis of randomized controlled trials comparing two or more diuretic strategies for fluid removal in critically ill adults. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials via Ovid, as well as trial registries, from inception to November 20, 2025. Two reviewers independently extracted data and assessed risk of bias using ROBUST-RCT. Certainty of evidence was evaluated using the GRADE approach for network meta-analysis. Treatment effects were summarized as odds ratios (ORs) or mean differences (MDs) with 95% credible intervals (CrIs).ResultsTwenty-six randomized controlled trials involving 1,652 participants were included. Evaluated interventions included bolus loop diuretics (19 studies), continuous loop infusion (15 studies), oral loop diuretics (5 studies), and loop diuretics combined with tolvaptan (8 studies), spironolactone (3 studies), thiazides (2 studies), acetazolamide (1 study), or triamterene (1 study). Compared with bolus loop diuretics, continuous loop infusion had an uncertain effect on mortality (OR 1.26; 95% CrI 0.62 to 2.55; very low certainty) and may increase ICU length of stay (MD 1.56 days; 95% CrI -0.02 to 3.16; low certainty). Tolvaptan monotherapy may reduce acute kidney injury compared with bolus or continuous loop diuretics (OR 0.12; 95% CrI 0.01 to 0.87; low certainty), although no studies evaluated its effect on the need for renal replacement therapy. For most other comparisons and outcomes, the certainty of evidence was low or very low.ConclusionsAvailable evidence comparing diuretic strategies for fluid removal during ICU-level care is limited, clinically heterogeneous, and derived largely from heart failure and post-cardiovascular surgery populations. Bolus loop diuretics were at least comparable to alternate diuretic strategies for patient important outcomes in critically ill adults, but this was based mostly on low or very low certainty evidence. Tolvaptan monotherapy may decrease acute kidney injury, but its effect on subsequent need for RRT and mortality remains uncertain.

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Thiamin is a water-soluble vitamin essential for energy metabolism. Patients on long-term diuretics, particularly those with heart disease, are at risk of thiamin deficiency (TD) due to increased urinary loss, which may impact cardiac function. We evaluated changes in thiamin pyrophosphate effect (TPPE) values after 4 weeks of thiamin supplementation compared to placebo in pediatric heart disease patients receiving diuretics. The secondary objectives included assessing changes in left ventricular ejection fraction (LVEF) and identifying factors associated with TPPE changes. In this triple-blinded, randomized controlled trial, we recruited 45 children (aged 1 month to 15 years) with heart disease with increased pulmonary blood flow or congestive heart failure, all on diuretics for ≥ 1 month. Participants were randomly allocated to receive thiamin 25 mg/day, thiamin 50 mg/day, or placebo for 4 weeks. TD was defined as TPPE values ≥ 15%. At baseline, 9 of 45 participants (20%) had TD. After 4 weeks, no significant differences in changes in TPPE values (p = 0.540) or LVEF (p = 0.441) were observed among the three groups. Multiple linear regression showed that furosemide dosage was independently associated with TPPE changes (β: +0.36, p = 0.015), indicating a dose-dependent association with thiamin status. Thiamin supplementation at 25 mg/day or 50 mg/day did not significantly improve TPPE values or LVEF. However, furosemide dosage correlated with TPPE changes, indicating a need for tailored thiamin supplementation strategies in pediatric heart disease patients on diuretics. For those with TD, doses exceeding 50 mg/day may be necessary.Trial registration NCT03989700 (ClinicalTrials.gov). Date of registration: 18/06/2019.

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