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Hypertension is associated with increased risk of stroke and bleeding in patients with atrial fibrillation (AF). In the present study, we aimed to investigate the influence of hypertension status in patients with AF receiving treatment with non-vitamin K antagonist oral anticoagulants (NOACs). PubMed, Embase, and Cochrane Library were searched from the inception of each database to November 2017. Randomized controlled trials (RCTs) that evaluated NOACs versus warfarin in patients with AF and hypertension were identified. A meta-analysis was performed using random- or fixed-effects models according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five trials (72,967 patients, including 51,378 patients with hypertension) were enrolled. NOACs significantly reduced the risk of stroke and systemic embolism (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.81–0.94, n = 51,378 patients), hemorrhagic stroke (HR 0.55, 95% CI 0.41–0.74, n = 28,818 patients), death from any cause (HR 0.91, 95% CI 0.85–0.97, n = 43,101 patients), major bleeding (HR 0.78, 95% CI 0.74–0.83, n = 51,378 patients) and intracranial bleeding (HR 0.50, 95% CI 0.38–0.67, n = 27,185 patients). The benefits of NOACs in comparison with warfarin were consistent in AF patients with or without hypertension (Pinteraction for all outcomes > 0.05). Our findings suggest that NOACs can be recommended for the prevention of stroke or systemic embolism in patients with AF and hypertension.

To evaluate the association between severe pulmonary embolism events and bevacizumab, we conducted the first meta-analysis evaluating the incidence and risk of pulmonary embolism associated with bevacizumab-based therapy. We searched PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov up to September 2016 for randomized controlled trials comparing bevacizumab with no bevacizumab on cancer patients. Incidence rates, relative risks, and 95% confidence intervals were calculated using fixed- or random-effects models. The primary end point was the association of bevacizumab with pulmonary embolism. Subgroup analyses were performed according to tumor type, dose, and publication status. In total, 23 randomized controlled trials were included. For patients receiving bevacizumab, the overall incidence of severe pulmonary embolism events was 1.76% (95% confidence interval = 1.25%–2.27%). Cancer patients treated with bevacizumab did not increase the risk of pulmonary embolism events (relative risk = 1.00, 95% confidence interval = 0.80–1.25). No significant differences in pulmonary embolism incidence or risk among subgroup analyses were observed. No evidence of publication bias was observed. This study suggested that bevacizumab may not increase the risk of pulmonary embolism in cancer patients.

Object The aim of this study was to evaluate the effectiveness of clodronate in the adjuvant therapy of early breast cancer on patient survival. Methods We performed a literature search to identify studies that investigated the effects of clodronate treatment on early breast cancer. Random and fixed-effect meta-analytical models were used where indicated and between-study heterogeneity was assessed. The primary study end-points were overall survival. Secondary end-points were bone metastasis-free survival and non-skeletal metastasis (mainly visceral metastases) free survival. Results Four randomised controlled trials met the inclusion criteria. Risk ratio (95% confidence interval (CI)) of overall survival was 0.84 (0.56–1.26); risk ratio (95% CI) of bone metastasis-free survival was 0.77 (0.58–1.02); risk ratio (95% CI) of non-bone metastasis-free survival was 0.89 (0.61–1.30). Outcomes after sensitivity analysis were: risk ratio (95% CI) of overall survival was 0.71 (0.52–0.96); risk ratio (95% CI) of bone metastasis-free survival was 0.70 (0.56–0.86); risk ratio (95% CI) of non-bone metastasis-free survival was 0.76 (0.64–0.92). Conclusion Compared with the control arm, adjuvant treatment with clodronate may improve the overall survival, bone metastasis-free survival and non-bone metastasis-free (mainly visceral metastases) survival in patients with early breast cancer. However, further meta-analyses involving all known randomised trials with analysis of sub-groups by age or menopausal status, accessing original trial data, should be performed.

ObjectiveTo compare the rate of moderate to severe exacerbations between triple therapy and dual therapy or monotherapy in patients with chronic obstructive pulmonary disease (COPD).DesignSystematic review and meta-analysis of randomised controlled trials.Data sourcesPubMed, Embase, Cochrane databases, and clinical trial registries searched from inception to April 2018.Eligibility criteriaRandomised controlled trials comparing triple therapy with dual therapy or monotherapy in patients with COPD were eligible. Efficacy and safety outcomes of interest were also available.Data extraction and synthesisData were collected independently. Meta-analyses were conducted to calculate rate ratios, hazard ratios, risk ratios, and mean differences with 95% confidence intervals. Quality of evidence was summarised in accordance with GRADE methodology (grading of recommendations assessment, development, and evaluation).Results21 trials (19 publications) were included. Triple therapy consisted of a long acting muscarinic antagonist (LAMA), long acting β agonist (LABA), and inhaled corticosteroid (ICS). Triple therapy was associated with a significantly reduced rate of moderate or severe exacerbations compared with LAMA monotherapy (rate ratio 0.71, 95% confidence interval 0.60 to 0.85), LAMA and LABA (0.78, 0.70 to 0.88), and ICS and LABA (0.77, 0.66 to 0.91). Trough forced expiratory volume in 1 second (FEV1) and quality of life were favourable with triple therapy. The overall safety profile of triple therapy is reassuring, but pneumonia was significantly higher with triple therapy than with dual therapy of LAMA and LABA (relative risk 1.53, 95% confidence interval 1.25 to 1.87).ConclusionsUse of triple therapy resulted in a lower rate of moderate or severe exacerbations of COPD, better lung function, and better health related quality of life than dual therapy or monotherapy in patients with advanced COPD.Study registrationProspero CRD42018077033.

Osteoporosis (OP), which is a common bone disease associated with reduced bone mineral density and disordered bone microstructure, may result in an increased risk of bone fracture. The present study aimed to investigate the frequency of alendronate (Aln)-associated upper gastrointestinal tract adverse events (GIAEs) in postmenopausal women with OP. The following databases were searched in order to identify relevant studies: Medline (using PubMed as the search engine), Embase, the Web of Science and the Cochrane Central Register of Controlled Trials (up to December 2014). Studies were selected for inclusion if they were randomized, double-blind, placebo-controlled trials, which had investigated the safety of Aln versus a placebo for the treatment of postmenopausal women with OP. The primary outcomes of the included studies were total adverse events (AEs) and upper GIAEs, whereas individual upper GIAEs were considered as secondary outcomes. The general characteristics and outcomes of each study were abstracted by two independent researchers, and Review Manager 5.3 software was used for data syntheses and the meta-analysis. A total of nine studies, including 15,192 randomized patients, met the inclusion criteria and contributed to some or all of the meta-analysis outcomes. The Mantel-Haenszel method was used to calculate risk ratios, and their 95% confidence intervals (CI) were determined using either the fixed or random effects model, depending on the level of heterogeneity. The relative risk (95% CI) of AEs associated with Aln treatment, as compared with the placebo group, was 1.01 (0.97-1.06), and the relative risk (95% CI) of discontinued Aln treatment due to AEs was 1.04 (0.91-1.19). In addition, the relative risk (95% CI) of upper GIAEs was 1.02 (0.99-1.06), and the relative risk (95% CI) of discontinued Aln treatment due to upper GIAEs was 1.23 (0.97-56). In addition, these results remained robust to sensitivity analyses. The results of the present study suggested that Aln has a good GI tract tolerability, and that daily treatment with 10 mg Aln sodium does not increase the risk of GIAEs in postmenopausal women with OP.

Introduction It has been suggested that vitamin D is effective to prevent mortality. However, there is no consistent conclusion that the effects of vitamin D supplementation on all-cause mortality are associated with duration of treatment. We conducted a meta-analysis regarding this issue in an effort to provide a more robust answer. Methods A comprehensive search in a number of databases, including MEDLINE, Embase and The Cochrane Central Register of Controlled Trials, was conducted for collecting randomized controlled trials (RCTs) on vitamin D supplementation preventing mortality. Two investigators independently screened the literature according to the inclusive and exclusive criteria and the relative data were extracted. Data analysis was performed by using Review Manager 5.0 software. Results Data from forty-two RCT s were included. Vitamin D therapy significantly decreased all-cause mortality with a duration of follow-up longer than 3 years with a RR (95% CI) of 0.94 (0.90–0.98). No benefit was seen in a shorter follow-up periods with a RR (95% CI) of 1.04 (0.97–1.12). Results remain robust after sensitivity analysis. The following subgroups of long-term follow-up had significantly fewer deaths: female only, participants with a mean age younger than 80, daily dose of 800 IU or less, participants with vitamin D insufficiency (baseline 25-hydroxyvitamin D level less than 50 nmol/L) and cholecalciferol therapy. In addition, the combination of vitamin D and calcium significantly reduced mortality and vitamin D alone also had a trend to decrease mortality in a longer time follow up. Conclusions The data suggest that supplementation of vitamin D is effective in preventing overall mortality in a long-term treatment, whereas it is not significantly effective in a treatment duration shorter than 3 years. Future studies are needed to identify the efficacy of vitamin D on specific mortality, such as cancer and cardiovascular disease mortality in a long-term treatment duration.