1.
Tolvaptan for Heart Failure in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis.
Sen, J, Chung, E, McGill, D
Heart, lung & circulation. 2018;(8):928-939
Abstract
BACKGROUND Heart failure (HF) is frequently associated with renal impairment. Tolvaptan is reported to be effective in treating congestion in HF without significant electrolyte loss compared to conventional diuretics. However, the safety and efficacy of its use in patients with chronic kidney disease (CKD) is uncertain. This systematic review and meta-analysis evaluated the efficacy and safety outcomes of tolvaptan for HF management in patients with CKD, with a focus at a physiologic basis related to safety. METHODS We searched for observational studies and randomised clinical trials (RCTs) that assessed the effects of tolvaptan against placebo or standard care in adult patients with HF and CKD. Our protocol was registered with PROSPERO (number CRD42017052775). RESULTS Seventeen studies were included in the qualitative review and six in the meta-analysis involving 1597 patients. Tolvaptan was associated with an increase in sodium concentration. No significant differences in change of eGFR and serum creatinine were found between tolvaptan and control groups. Urine flow rate appears to increase significantly with tolvaptan compared to baseline (p<0.0001). The meta-analysis demonstrated no heterogeneity between studies but the possibility of publication bias due to incomplete reporting in excluded studies and lack of RCTs. CONCLUSIONS The safety profile of tolvaptan appears acceptable for patients with HF and CKD. There is evidence for an improvement in serum sodium and reduction in body water without deterioration in renal function. Further research is needed to elucidate the long-term benefits of tolvaptan as an adjunct or alternative to diuretics in such patients.
2.
Network meta-analysis of lorcaserin and oral hypoglycaemics for patients with type 2 diabetes mellitus and obesity.
Neff, LM, Broder, MS, Beenhouwer, D, Chang, E, Papoyan, E, Wang, ZW
Clinical obesity. 2017;(6):337-346
Abstract
In addition to weight loss, randomized controlled trials have shown improvement in glycaemic control in patients taking lorcaserin. The aim of this study aim was to compare adding lorcaserin or other glucose lowering medications to metformin on weight and glycaemic control. A systematic review and network meta-analysis of randomized controlled trials were conducted. Included studies (published 1990-2014) were of lorcaserin or glucose lowering medications in type 2 diabetic patients compared to placebo or different active treatments. Studies had to report ≥1 key outcome (change in weight or HbA1c, % HbA1c <7, hypoglycaemia). Direct meta-analysis was performed using DerSimonian and Laird random effects models, and network meta-analysis with Bayesian Markov-chain Monte Carlo random effects models; 6552 articles were screened and 41 included. Lorcaserin reduced weight significantly more than thiazolidinediones, glinides, sulphonylureas and dipeptidyl peptidase-4 inhibitors, some of which may have led to weight gain. There were no significant differences in weight change between lorcaserin and alpha-glucoside inhibitors, glucagon-like peptide-1 agonists and sodium/glucose cotransporter 2 inhibitors. Network meta-analysis showed lorcaserin was non-inferior to all other agents on HbA1c reduction and % achieving HbA1c of <7%. The risk of hypoglycaemia was not significantly different among studied agents except that sulphonylureas were associated with higher risk of hypoglycaemia than lorcaserin. Although additional studies are needed, this analysis suggests in a population of patients with a body mas index of ≥27 who do not achieve glycaemic control on a single agent, lorcaserin may be added as an alternative to an add-on glucose lowering medication.
3.
The short-term and long-term effects of tolvaptan in patients with heart failure: a meta-analysis of randomized controlled trials.
Xiong, B, Huang, Y, Tan, J, Yao, Y, Wang, C, Qian, J, Rong, S, Deng, S, Cao, Y, Zou, Y, et al
Heart failure reviews. 2015;(6):633-42
Abstract
A comprehensive evaluation of the benefits of tolvaptan for the management of heart failure (HF) is lacking. The objective of this meta-analysis was to assess the short-term and long-term effects of tolvaptan in patients with HF. Articles were searched from PubMed, MEDLINE and Cochrane Library before March 31, 2015. Randomized controlled trials enrolling adult HF patients and reporting the all-cause mortality, cardiac events, body weight change or changes of serum electrolytes including sodium, potassium and creatinine were included in our meta-analysis. Ten studies covering 5574 patients met the inclusion criteria. Based on the data of meta-analysis, tolvaptan had no impact on the all-cause mortality [relative risk (RR) 0.96; 95 % confidence interval (CI) 0.87-1.06; P = 0.40] and incidence of cardiac events (RR 1.03; 95 % CI 0.96-1.11; P = 0.40) of HF patients. Furthermore, in comparison with control treatments, tolvaptan significantly decreased the body weight [weight mean difference (WMD), -0.87; 95 % CI -1.03 to -0.71; P < 0.001] and statistically increased serum sodium (WMD, 2.58; 95 % CI -1.83 to 3.33; P < 0.001) without any change in serum potassium (WMD, 0.01; 95 % CI -0.03 to 0.05; P = 0.577). However, serum creatinine may be increased slightly by tolvaptan (WMD, 0.05; 95 % CI 0.03-0.07; P < 0.001). This meta-analysis suggests that in HF patients, tolvaptan may not bring long-term benefits, but it effectively improves the volume overload and hyponatremia without obvious increases in serum potassium and creatinine. Hence, tolvaptan is likely to be a promising diuretic for the treatment of HF.
4.
Vasopressin receptor antagonists for the treatment of hyponatremia: systematic review and meta-analysis.
Rozen-Zvi, B, Yahav, D, Gheorghiade, M, Korzets, A, Leibovici, L, Gafter, U
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2010;(2):325-37
Abstract
BACKGROUND In patients with euvolemic and hypervolemic hyponatremia, the effect of vasopressin antagonists is yet undefined. STUDY DESIGN Systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING & POPULATION In- and outpatients with euvolemic or hypervolemic hyponatremia. SELECTION CRITERIA FOR STUDIES We included all RCTs regardless of publication status or language. INTERVENTION Vasopressin antagonists with or without fluid restriction versus placebo or no treatment with or without fluid restriction. OUTCOMES Response rate defined as normalization of serum sodium level or significant increase in serum sodium level at 3-7 days (primary) and later, change from baseline serum sodium level at 3-7 days and later, adverse events, rate of rapid sodium level correction, and rate of hypernatremia. RESULTS 15 RCTs were identified. Vasopressin antagonist treatment significantly increased response rate both early (RR, 3.15; 95% CI, 2.27-4.37; 11 trials) and late (RR, 2.27; 95% CI, 1.79-2.89; 4 trials). Response rates were high in trials assessing mostly euvolemic patients and those assessing mostly hypervolemic patients, with greater effect estimate in the former. Change from baseline serum sodium level was significantly increased both early (weighted mean difference, 5.27 mEq/L; 95% CI, 4.27-6.26, 13 trials) and late (weighted mean difference, 3.49 mEq/L; 95% CI, 2.56-4.41, 8 trials). Although there was an increased rate of rapid sodium correction (RR, 2.52; 95% CI, 1.26-5.08, 8 trials) with vasopressin antagonists, hypernatremia rates were not significantly higher (RR, 2.21; 95% CI, 0.61-7.96; 5 trials), adverse events were not increased, and there were no reports of osmotic demyelination syndrome. LIMITATIONS Significant heterogeneity in the primary outcome. CONCLUSIONS Vasopressin antagonists are effective for the treatment of hypervolemic and euvolemic hyponatremia.