Safety and efficacy of lithium in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This study provides a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the safety and efficacy of lithium in amyotrophic lateral sclerosis (ALS) patients. METHODS: PubMed, Web of Science, Cochrane CENTRAL, Scopus, and Your Journals@Ovid were searched up to 9 December 2022. RCTs investigating lithium, either alone or with any supplement, in ALS patients were included. Meta-analysis was performed using RevMan and results are presented in forest plot. RESULTS: Four RCTs with 469 patients met the inclusion criteria and were included in our study. Lithium doses varied among the included studies and one study used a combined therapy of lithium with valproate. Meta-analysis showed no difference between lithium and placebo regarding severe adverse events (odds ratio = 1.13, 95% confidence interval: 0.73 to 1.75, P = 0.58). No significant differences were observed with regard to survival rate between the two groups (hazard ratio = 0.95, 95% confidence interval: 0.65 to 1.37, P = 0.77). There were also no significant differences between the two groups with regard to average changes of revised amyotrophic lateral sclerosis functional rating scale (P = 0.35) and forced vital capacity percentage predicted (P = 0.73). Subgroup analysis showed no significant differences regarding all investigated outcomes either for lithium alone or lithium with valproate. CONCLUSION: Current evidence suggests a safety profile with no benefit of lithium for ALS. However, given the limited number of RCTs and the safety findings, we recommend further well-designed RCTs to investigate lithium and valproate in ALS patients.

Meta-Analysis on the Safety and Efficacy of Sodium Glucose Cotransporters 2 Inhibitors in Patients With Heart Failure With and Without Diabetes.

Heart failure (HF) is the most common cardiovascular cause of hospitalization in patients over 60 years, affecting about 64.3 million patients worldwide. Few studies have investigated the role of sodium glucose cotransporter inhibitors (SGLT2Is) in patients with HF without and without diabetes. Thus, we conducted our meta-analysis to further investigate the role of SGLT2I role in patients with HF without and without diabetes. PubMed, Scopus, Web of Science, and Embase were searched. All clinical trials that compared the effect of SGLT2Is versus placebo on patients with HF were included. Dichotomous data were extracted, pooled as risk ratio (RR) with 95% confidence interval (CI), and analyzed using RevMan version 5.3 for windows using the Mantel-Haenszel method. A total of 13 randomized clinical trials were included for analysis, with a total number of 75,287 patients. SGLT2Is significantly lowered the risk of hospitalization for HF in patients with (RR = 0.68, 95% CI 0.63 to 0.74) and without diabetes (RR = 0.75, 95% CI 0.62 to 0.89). Furthermore, they lowered the mortality risk in both patients with diabetes with statistical significance (RR = 0.87, 95% CI 0.77 to 0.99), yet without statistical significance in patients without diabetes (RR = 0.93, 95% CI 0.70 to 1.23). Further analyses for serious adverse events were conducted, and SGLT2I showed a significant lower risk in patients with diabetes (RR = 0.94, 95% CI 0.90 to 0.98) and without diabetes (RR = 0.72, 95% CI 0.38 to 1.39). in patients with diabetes, SGLT2Is significantly reduced cardiovascular mortality, HHF, and serious adverse events. However, in patients without, despite showing a significant reduction in HHF, SGLT2I reduced cardiovascular mortality or serious adverse events but without statistical significance.