Bapineuzumab for mild to moderate Alzheimer’s disease: a meta-analysis of randomized controlled trials

Abstract Background Alzheimer’s disease (AD) is a globally prevalent neurodegenerative condition, clinically characterized by progressive memory loss and gradual impairment of cognitive functions. Bapineuzumab is a fully humanized monoclonal antibody that binds to neurotoxic amyloid proteins in the brain, enhancing their clearance. We performed this systematic review and meta-analysis to evaluate the safety and efficacy of bapineuzumab in patients with mild to moderate Alzheimer’s disease. Methods We performed a web-based literature search of PubMed, Ovid, EBSCO, Scopus, Embase, Cochrane CENTRAL, and web of science using the relevant keywords. Data were extracted from eligible records and pooled as mean difference (MD) or risk ratio (RR) values with their 95% confidence interval (CI), using Review Manager software (version 5.3 for windows). Heterogeneity was measured by Chi-square and I-square tests. Result The pooled effect estimate from six randomized clinical trials (n = 2380) showed that bapineuzumab significantly reduced the cerebrospinal fluid concentration of phosphorylated tau proteins (Standardized MD = −5.53, 95% CI [−8.29, −2.76]). However, the bapineuzumab group was not superior to the placebo group in terms of change from baseline in Alzheimer’s disease assessment scale (ADAS)-Cog11 (MD = 0.14, 95% CI [−0.72, 0.99]), disability assessment for dementia (DAD) scale (MD = 1.35, 95% CI [−1.74, 4.43]), and mini-mental state examination (MMSE) scores (MD = 0.08, 95% CI [−0.31, 0.47]). Regarding safety, bapineuzumab increased the risk of serious treatment-emergent adverse events (RR = 1.18, 95% CI [1.02, 1.37]) and cerebral vasogenic edema (RR = 40.88, 95% CI [11.94, 135.95]). All bapineuzumab doses (0.15, 0.5, 1, and 2 mg/kg) were similar to placebo in terms of change from baseline in ADAS-cog11, DAD, and MMSE scores, except for the 0.15 mg/kg dose, which caused a significant worsening on the ADAS-cog11 scale (MD = 5.6, 95% CI [0.22, 10.98]). Conclusions Considering the lack of clinical efficacy, combined with the significant association with serious adverse events, bapineuzumab should not be used to treat patients with mild to moderate AD. Future studies should investigate the effect of combining bapineuzumab with other therapeutic strategies and reevaluate the efficacy of targeting amyloid β proteins in AD therapy

Efficacy and safety of transcatheter aortic valve replacement in aortic stenosis patients at low to moderate surgical risk: a comprehensive meta-analysis

Abstract Background Recently, transcatheter aortic valve replacement (TAVR) has become the procedure of choice in high surgical risk patients with aortic stenosis (AS). However, its value is still debated in operable AS cases. We performed this meta-analysis to compare the safety and efficacy of TAVR to surgical aortic valve replacement (SAVR) in low-to-moderate surgical risk patients with AS. Methods A systematic search of five authentic databases retrieved 11 eligible studies (20,056 patients). Relevant Data were pooled as risk ratios (RRs) or standardized mean differences (SMD), with their 95% confidence interval, using Comprehensive Meta-Analysis and RevMan software for windows. Results At one-year of follow-up, the pooled effect-estimates showed no significant difference between TAVR and SAVR groups in terms of all-cause mortality (RR 1.02, 95% CI [0.83, 1.26], stroke (RR 0.83, 95%CI [0.56, 1.21]), myocardial infarction (RR 0.82, 95% CI [0.57, 1.19]), and length of hospital stay (SMD -0.04, 95% CI [−0.34, 0.26]). The incidence of major bleeding (RR 0.45, 95% CI [0.24, 0.86]) and acute kidney injury (RR 0.52, 95% CI [0.30, 0.88]) was significantly lower in the TAVR group, compared to the SAVR group. However, TAVR was associated with a higher risk of permanent pacemaker implantation (RR 2.57, 95% CI [1.36, 4.86]), vascular-access complications at 1 year (RR 1.99, 95%CI [1.04, 3.80]), and paravalvular aortic regurgitation at 30 days (RR 3.90, 95% CI [1.25, 12.12]), compared to SAVR. Conclusions Due to the comparable mortality rates in SAVR and TAVR groups and the lower risk of life-threatening complications in the TAVR group, TAVR can be an acceptable alternative to SAVR in low-to-moderate risk patients with AS. However, larger trials with longer follow-up periods are required to compare the long-term outcomes of both techniques