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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BackgroundHealthcare providers should balance the potential risks and benefits of chronic diuretic use, particularly in older adults, as with age, diuretic benefits may decline and risks increase. A comprehensive synthesis and critical evaluation of the available evidence on chronic diuretic treatment effects is currently lacking.MethodsWe conducted an umbrella review of systematic reviews and meta-analyses published since 2018 on health outcomes associated with diuretic use in randomized-controlled trials (RCTs). We conducted random-effects meta-analysis for pooled effect estimates and narratively summarized data that could not be pooled.ResultsWe included 741 effect estimations from 117 systematic reviews (SRs) on 1566 RCTs in individuals aged 62 ± 6 years. Of our 33 meta-analyses, 11 provided convincing, high-quality evidence: finerenone reduced the risk of cardiovascular (CV) mortality and end-stage kidney disease in individuals with chronic kidney disease (CKD) and/or type 2 diabetes (T2D). Torasemide reduced the risk of heart failure-related hospitalization (HFH) more than furosemide in individuals with HF. Thiazides reduced CV events in individuals with hypertension. Mineralocorticoid receptor antagonists (MRAs) reduced HFH, but also increased hyperkalemia risk in individuals with HF. MRAs also reduced the risk of atrial fibrillation in those with HF or CVD, and reduced HFH, major adverse cardiovascular events (MACEs), > 40% eGFR decrease, and composite kidney outcomes in individuals with CKD and/or T2D. Lower quality evidence suggests that in older (≥ 65 years), but not in younger adults, diuretics may reduce CV mortality, but also increase adverse event (AE) risk.ConclusionsOur umbrella review offers a comprehensive and up-to-date evaluation of the benefits and harms of diuretics. However, further research is needed to establish their efficacy and safety in populations commonly seen in clinical practice, especially older adults living with multimorbidity and frailty.

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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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ObjectiveTo gain initial insight into the efficacy to lower intracranial pressure (ICP), side effects, and effects on cognition of five drugs commonly used to treat idiopathic intracranial hypertension (IIH).BackgroundLimited clinical data exist for the treatment for IIH. Impaired cognition is recognized in IIH and can be exacerbated by medications.MethodsThis human experimental medicine study was a secondary analysis that focused on an unblinded randomized, sequential, cross-over extension of a previously completed randomized controlled trial. This study evaluated females with active IIH, recruited from University Hospital Birmingham, UK. Participants were treated, in randomized order, for 2 weeks with acetazolamide, amiloride, furosemide, spironolactone, and topiramate; assessment was at baseline and 2 weeks with a minimum 1-week drug washout between drugs. The primary outcome was change in ICP at 2 weeks post-drug administration. The cognitive evaluation was an exploratory study of the trial. ICP was recorded with telemetric, intraparenchymal ICP monitors (Raumedic, Hembrechts, Germany). Adverse events were recorded, and cognition was assessed utilizing the National Institutes of Health Toolbox Cognitive Battery.ResultsFourteen participants were recruited and evaluated by intention-to-treat analysis. Mean (standard deviation) body mass index was 37.3 (7.0) kg/m2 and ICP was 33.2 (7.1) cm cerebrospinal fluid (CSF) at baseline. ICP fell with four drugs (mean [standard error (SE)]), acetazolamide -3.3 (1.0) mmHg, p = 0.001, furosemide -3.0 (0.9) mmHg, p = 0.001, spironolactone -2.7 (0.9) mmHg, p = 0.003, and topiramate -2.3 (0.9) mmHg, p = 0.010. There was no significant difference between drugs. Side effects were common with acetazolamide (100%, 11/11) and topiramate (93%, 13/14). Baseline cognitive performance was impaired, T-score (mean [SE]) 37.2 (2.6). After treatment, there was a further significant reduction in the fluid cognition domain (ability to process and integrate) with acetazolamide (mean T-score [SE]), -5.0 (2.6), p = 0.057 and topiramate -4.1 (2.0), p = 0.061.ConclusionsAcetazolamide, furosemide, spironolactone, and topiramate marginally reduced ICP. While their effects were not significant, this study was not powered to detect a difference between drugs. Participants reported significant side effects with acetazolamide and topiramate including cognitive decline. Cognitive measures were impaired by acetazolamide and topiramate. Therapeutics with greater efficacy and a favorable side effect profile are an unmet need in the treatment of IIH.

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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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