Tolvaptan 7.5mg tablets

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.

Abstract licence: CC BY

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder, with tolvaptan remaining the primary disease-modifying therapy. SGLT2 inhibitors have demonstrated robust renoprotection across the chronic kidney disease (CKD) spectrum, yet patients with ADPKD have been systematically excluded from pivotal trials due to concerns over vasopressin-mediated cystogenesis. This systematic review and meta-analysis aimed to pool available evidence on SGLT2 inhibitor use in patients with ADPKD. This systematic review and meta-analysis were registered with PROSPERO (CRD420261324155) and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta‑Analyses (PRISMA) guidelines. Five databases were searched through February 2026 for studies including ADPKD patients receiving any SGLT2 inhibitor. Quality was assessed using the Risk of Bias 2 (RoB2), Newcastle-Ottawa Scale, and Joanna Briggs Institute (JBI) tools, depending on the study design. Eight studies encompassing 3,180 patients were included, comprising one randomized controlled trial (RCT), one target trial emulation study, and six retrospective observational studies. In comparative analyses, SGLT2 inhibitor use was associated with a statistically significant attenuation of estimated glomerular filtration rate (eGFR) decline (pooled mean difference {MD}: 1.344 mL/min/1.73 m²/year; 95% CI: 0.836-1.852). A significant hemoglobin increase was observed in both comparative (MD: 0.66 g/dL) and single-arm analyses (MD: 0.55 g/dL). Subgroup analyses suggested a greater eGFR benefit in non-diabetic patients, though differences were not statistically significant. Our findings suggest that SGLT2 inhibitors may attenuate eGFR decline and improve hemoglobin in ADPKD, with the initial eGFR dip representing a class effect rather than harm, supporting their prospective evaluation in dedicated randomized trials. These findings should be interpretedwith cuchion the predominantly observational study designs, heterogeneous patient populations.

Abstract licence: CC BY

Many patients hospitalized with acute heart failure (AHF) do not respond adequately to initial intravenous loop diuretic therapy, and residual congestion at discharge is associated with adverse outcomes. We conducted a systematic review and meta-analysis of randomized controlled trials comparing loop diuretics alone versus loop diuretics in combination with add-on pharmacotherapy in adults hospitalized with AHF. PubMed, Embase, and CENTRAL were searched from inception to May 7, 2025. Efficacy outcomes included mortality, hospital readmission, hospital length of stay (LOS), change in body weight, and urine output (UO). Safety outcomes included worsening renal function, worsening heart failure (WHF), hypokalemia, and serious adverse events. Twenty-four randomized studies were identified, with 22 included in the meta-analysis. Sodium-glucose cotransporter 2 (SGLT2) inhibitors significantly reduced mortality [risk ratio (RR), 0.60 (95% confidence interval [CI], 0.38-0.94)], WHF [RR, 0.64 (95% CI, 0.43-0.96)], serious adverse events [RR, 0.74 (95% CI, 0.60-0.92)], and body weight [mean difference (MD), -1.05 (95% CI, -1.97 to -0.13) kg]. Tolvaptan was associated with greater weight reduction [MD, -0.98 (95% CI, -1.25 to -0.70) kg] and increased UO [MD, 1.15 (95% CI, 0.16-2.14) L]. Add-on hydrochlorothiazide (HCTZ) increased UO [MD, 0.95 (95% CI, 0.47-1.43) L] and decreased LOS [MD, -1.38 (95% CI, -2.40 to -0.36) days] but increased the risk of worsening renal function [RR, 2.03 (95% CI, 1.10-3.74)] and hypokalemia [RR, 2.31 (95% CI, 1.51-3.52)]. Overall, the combination with SGLT2 inhibitors, tolvaptan, and HCTZ improved surrogate markers of decongestion in AHF. SGLT2 inhibitors were associated with reduced mortality and WHF, whereas HCTZ shortened hospital LOS but increased the risk of renal dysfunction and hypokalemia.

Abstract licence: CC BY

Fluid 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. We 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). Twenty-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. Available 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.

Abstract licence: CC BY-NC-ND

BackgroundHeart failure is a life-threatening disease affecting millions worldwide. Tolvaptan is the first FDA-approved orally active nonpeptide vasopressin 2 receptor antagonist to be used in hypervolemic hyponatremia, heart failure, cirrhosis, etc. In clinical trials, tolvaptan impacts short-term in increasing water excretion, and restoring Na+ and dyspnoea. Aims & ObjectivesThe objective is to analyze the outcomes of tolvaptan in existing cases of heart failure. MethodologyWe conducted a database search of the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials and RCTs till 1st September 2019 were included following PRISMA guidelines after being matched with inclusion and exclusion criteria. 21 RCTs were included with 7,357 patients receiving tolvaptan and 7,273 patients being the control group. We used the MESH strings such as 'tolvaptan', 'vasopressin V2 receptor blocker', 'acute heart failure', and 'acute decompensated heart failure'. ResultsMeta-analysis showed that Tolvaptan was associated with a significant reduction in edema (RR = 1.05, 95% CI = 1.019-1.081, p=0.001) and significant body weight reduction (Control-SMD = -0.489, 95% CI =-0.637 to -0.342, p<0.001)&(Placebo-SMD = -0.425, 95% CI = -0.425 to -0.382, p<0.001) It shows significant decrease in serum sodium levels (SMD = 0.678, 95% CI = 0.609 to 0.748, p<0.001). There was no significant decrease in all-cause mortality (Control-RR = 0.855, 95% CI 0.470 to 1.555, p=0.607)(Placebo-RR= 0.972, 95% CI = 0.879-1.074, p=0.575). Results for Worsening renal function in heart failure (Placebo-RR = 0.798 95% CI 0.619 to 1.028, p=0.081)(Control-RR = 1.349, 95% CI=0.927-1.964, p=0.118). ConclusionAlthough tolvaptan may significantly reduce edema, congestive symptoms and decreased body weight, it has no impact on all-cause mortality and worsening renal function in heart failure.

Abstract licence: CC BY 4.0

BackgroundDiuretic resistance complicates decongestion in heart failure (HF). Multiple add-on strategies are used, yet comparative efficacy and safety remain uncertain.ObjectivesThe objective of the study was to compare pharmacologic strategies for diuretic resistance in HF using a random-effects network meta-analysis of randomized controlled trials (RCTs).MethodsWe searched PubMed/Embase (January 2000-June 2024) for adult HF RCTs with diuretic resistance. Primary outcomes were 72-h urine output and standardized 72-h weight; secondary outcomes were heart-failure hospitalization and cardiovascular mortality; safety was acute kidney injury (AKI). A random-effects network meta-analysis pooled mean differences (MDs) for urine, standardized MDs (SMDs) for weight, and ORs for binary outcomes. Mortality was also assessed by follow-up-adjusted meta-regression of incidence rate ratios.ResultsNineteen RCTs (n = 9,685) were included. Compared with low-dose loop diuretics, 72-hour urine output increased with tolvaptan (MD: 1,840 mL; 95% CI: 441-3,240) and low-dose loop plus tolvaptan (MD: 1,643 mL; 95% CI: 53-3,234). For 72-hour weight change, hydrochlorothiazide (SMD: 1.33; 95% CI: 0.49-2.18) and tolvaptan (SMD: 0.69; 95% CI: 0.09-1.29) produced the greatest standardized reductions. Dapagliflozin (OR: 0.15; 95% CI: 0.03-0.73) and empagliflozin (OR: 0.19; 95% CI: 0.04-0.94) reduced heart failure hospitalizations. Follow-up-adjusted mortality, expressed as incidence rate ratios, was neutral to favorable but imprecise and consistent in ≤60-day sensitivity analyses. High-dose loop diuretics (OR: 2.27; 95% CI: 1.20-4.30) and hydrochlorothiazide (OR: 4.14; 95% CI: 2.03-8.42) were associated with increased acute kidney injury.ConclusionsIn HF with diuretic resistance, sodium-glucose cotransporter 2 inhibitors may lower rehospitalization with a favorable renal profile, whereas nephron-segment add-ons enhance short-term decongestion but warrant AKI/electrolyte monitoring; rankings are exploratory, and choices should emphasize absolute effects and 95% CIs.

Abstract licence: CC BY-NC-ND