Project description:BackgroundHigh-quality evidence from trials directly comparing single antiplatelet therapies in symptomatic peripheral arterial disease (PAD) to dual antiplatelet therapies or acetylsalicylic acid (ASA) plus low-dose rivaroxaban is lacking. Therefore, we conducted a network meta-analysis on the effectiveness of all antithrombotic regimens studied in PAD.MethodsA systematic search was conducted to identify randomized controlled trials. The primary endpoints were major adverse cardiovascular events (MACE) and major bleedings. Secondary endpoints were major adverse limb events (MALE) and acute limb ischaemia (ALI). For each outcome, a frequentist network meta-analysis was used to compare relative risks (RRs) between medication and ASA. ASA was the universal comparator since a majority of studies used ASA as in the reference group.ResultsTwenty-four randomized controlled trials were identified including 48,759 patients. With regard to reducing MACE, clopidogrel [RR 0.78, 95% confidence interval (CI) 0.66-0.93], ticagrelor (RR 0.79, 95% CI 0.65-0.97), ASA plus ticagrelor (RR 0.79, 95% CI 0.64-0.97), and ASA plus low-dose rivaroxaban (RR 0.84, 95% CI 0.76-0.93) were more effective than ASA, and equally effective to one another. As compared to ASA, major bleedings occurred more frequently with vitamin K antagonists, rivaroxaban, ASA plus vitamin K antagonists, and ASA plus low-dose rivaroxaban. All regimens were similar to ASA concerning MALE, while ASA plus low-dose rivaroxaban was more effective in preventing ALI (RR 0.67, 95% CI 0.55-0.80). Subgroup analysis in patients undergoing peripheral revascularization revealed that ≥ 3 months after intervention, evidence of benefit regarding clopidogrel, ticagrelor, and ASA plus ticagrelor was lacking, while ASA plus low-dose rivaroxaban was more effective in preventing MACE (RR 0.87, 95% CI 0.78-0.97) and MALE (RR 0.89, 95% CI 0.81-0.97) compared to ASA. ASA plus clopidogrel was not superior to ASA in preventing MACE ≥ 3 months after revascularization. Evidence regarding antithrombotic treatment strategies within 3 months after a peripheral intervention was lacking.ConclusionClopidogrel, ticagrelor, ASA plus ticagrelor, and ASA plus low-dose rivaroxaban are superior to ASA monotherapy and equally effective to one another in preventing MACE in PAD. Of these four therapies, only ASA plus low-dose rivaroxaban provides a higher risk of major bleedings. More than 3 months after peripheral vascular intervention, ASA plus low-dose rivaroxaban is superior in preventing MACE and MALE compared to ASA but again at the cost of a higher risk of bleeding, while other treatment regimens show non-superiority. Based on the current evidence, clopidogrel may be considered the antithrombotic therapy of choice for most PAD patients, while in patients who underwent a peripheral vascular intervention, ASA plus low-dose rivaroxaban could be considered for the long-term (> 3 months) prevention of MACE and MALE.
Project description:BackgroundPrevious studies have suggested an increased risk of hip fracture among patients with peripheral arterial disease (PAD), however, the results have been inconsistent. This meta-analysis was conducted with the aim to summarize all available evidence to better characterize the risk of incident hip fracture among these patients.Materials and methodsA comprehensive literature review was conducted using the MEDLINE and EMBASE databases through October 2017 to identify all cohort and case-control studies that compared the risk of subsequent hip fracture between patients with PAD and individuals without PAD. Effect estimates of the included studies were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird.ResultsThe systematic review process yielded six eligible cohort studies comprising 15,895 patients with PAD. There was a significant association between incident hip fracture and PAD with the pooled relative risk (RR) of 1.64 (95% CI, 1.17-2.29; I2, 80%), comparing patients with PAD and individuals without PAD. Subgroup analysis by study design revealed significant results for both prospective studies (pooled RR 1.60; 95% CI, 1.12-2.28; I2, 0%) and retrospective studies (pooled RR 1.72; 95% CI, 1.07-2.77; I2, 92%). The funnel plot is relatively asymmetric suggesting publication bias.ConclusionThis study found a significant association between PAD and hip fracture with the pooled RR of 1.64 (95% CI, 1.17-2.29) on comparing patients with PAD and individuals without PAD. Major limitations include high between-study heterogeneity, possibility of publication bias, and lack of data on the characteristics and type of hip fracture which may limit the clinical significance of the observations.
Project description:BACKGROUND:Peripheral arterial disease (PAD) is a common cause of disability and mortality. The reconstruction of blood circulation presents to be the key to treatment, which can be achieved by surgery and interventional therapy. Since 40% patients have lost the chance for the therapy, a new method is needed to reduce the amputation and mortality rate for "no-option" patients. The objective of our systematic review and meta-analysis was to evaluate the efficacy and safety of autologous implantation of stem cells in patients with PAD critically, compared with active controls and placebo. METHODS:Randomized controlled trials (RCTs) of autologous implantation of stem cells compared with placebo and control for PAD were included. Electronic medical databases including MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the Chinese Biomedical Literature Database, China National Knowledge Infrastructure (CNKI), and ClinicalTrials.gov were searched from initial period to September 2018. Independently, two reviewers screened citations, extracted data, and assessed the risk of bias according to the criteria of the Cochrane handbook. The quality of evidence was evaluated by GRADE evidence profile. The primary outcomes consisted of amputation rate, major amputation rate, ulcer healing rate, and side effects. The second outcomes included ankle-brachial index (ABI), transcutaneous oxygen tension (TcO2), pain-free walking distance (PFWD), and rest pain score. Statistical analysis was conducted via RevMan 5.3 and Stata 12.0. RESULTS:According to the twenty-seven RCTs, 1186 patients and 1280 extremities were included and the majority of studies showed a high risk of bias. Meta-analysis indicated that autologous stem cell therapy was more effective than conventional therapy on the healing rate of ulcers [OR = 4.31 (2.94, 6.30)]. There was also significant improvement in ABI [MD = 0.13 (0.10, 0.17)], TcO2 [MD = 0.13 (0.10, 0.17)], and PFWD [MD = 178.25 (128.18, 228.31)] while significant reduction was showed in amputation rate [OR = 0.50 (0.36, 0.69)] and rest pain scores [MD = - 1.61 (- 2.01, - 1.21)]. But the result presented no significant improvement in major limb salvage [0.66 (0.42, 1.03)]. Besides, stem cell therapy could reduce the amputation rate [OR = 0.50 (0.06, 0.45] and improve the ulcer healing rate [OR = 4.34 (2.96, 6.38] in DM subgroup. Eight trials reported the side effects of autologous stem cell therapy, and no serious side effects related to stem cells were reported. GRADE evidence profile showed all the quality evidence of outcomes were low. CONCLUSIONS:Based on the review, autologous stem cell therapy may have a positive effect on "no-option" patients with PAD, but presented no significant improvement in major limb salvage. However, the evidence is insufficient to prove the results due to high risk of bias and low-quality evidence of outcomes. Further researches of larger, randomized, double-blind, placebo-controlled, and multicenter trials are still in demand.
Project description:IntroductionPatients with peripheral arterial disease (PAD) are at increased risk for systemic arterial thromboembolic events. Females represent a unique subset of patients with PAD, who differ from males in important ways: they have smaller diameter vessels, undergo lower extremity bypass less frequently and experience higher rates of graft occlusion, amputation and mortality than males. Females also trend towards higher rates of major coronary events and cardiovascular mortality. Current guidelines recommend monoantiplatelet therapy (MAPT) for secondary prevention in patients with symptomatic PAD. However, indications for more intensive antithrombotic therapy in this cohort-especially among females who are frequently under-represented in randomised controlled trials (RCTs)-remain unclear. As newer antithrombotic therapies emerge, some RCTs have demonstrated differential effects in females versus males. A systematic review is needed to quantify the rates of arterial thromboembolic and bleeding events with different antithrombotic regimens in females with symptomatic PAD.Methods and analysisWe will search MEDLINE, Embase and the Cochrane Central Register of Controlled trials for published RCTs that include females with symptomatic PAD and compare full dose anticoagulation±antiplatelet therapy, dual pathway inhibition or dual antiplatelet therapy with MAPT. Title, abstract and full-text screening will be conducted in duplicate by three reviewers. Authors will be contacted to obtain sex-stratified outcomes as needed. Risk of bias will be assessed using the Cochrane Risk of Bias tool. Data will be extracted by independent reviewers and confirmed by a second reviewer. Quantitative synthesis will be conducted using Review Manager (RevMan) V.5 for applicable outcomes data. Planned subgroup analysis by PAD severity, vascular intervention and indication for antithrombotics will be conducted where data permits.Ethics and disseminationEthics approval is waived as the study does not involve primary data collection. This review will be submitted for publication in a peer-reviewed journal and for presentation at national and international scientific meetings.Trial registration numberThis protocol was registered with the PROSPERO International Prospective Register of Systematic Reviews (ID# CRD42020196933).
Project description:Background and objectivesBehçet's disease (BD) is a systemic vasculitis that is characterized by genital, oral, or skin lesions, uveitis, and vascular complications. Studies have shown that increased arterial stiffness is common in systemic immune and inflammatory diseases such as rheumatoid arthritis and systemic lupus erythematosus. However, current research has not yet determined whether patients with BD have increased arterial stiffness. This meta-analysis compares arterial stiffness parameters in subjects with a BD diagnosis to normal subjects.Subjects and methodsA comprehensive search of the MEDLINE and EMBASE databases was performed from the database beginning through May 2016. Observation studies were included in this analysis if they assessed the association between BD and arterial stiffness in adult subjects. BD patients met the International Study Group criteria for a diagnosis of Behçet's disease. Aortic stiffness was assessed using carotid-femoral pulse wave velocity (PWV) measurements as an indicator. Pooled mean difference (MD) of PWV and 95% confidence intervals (CI) were calculated using a random-effect, generic inverse variance meta-analysis. The between-study heterogeneity of effect-size was quantified using the Q statistic and I2.ResultsData were extracted from four observational studies that included 303 subjects. PWV is significantly higher in patients with Behçet's disease compared with controls (MD=0.74;95%, CI: 0.28-1.20, p=0.002, I2=63%).ConclusionIn this meta-analysis, we observed that PWV, an ideal indicator of arterial stiffness, is increased in patients with Behçet's disease compared with the controls. Prospective studies in a large population should be done to determine the pathophysiological and prognostic implications of increased arterial stiffness in BD.
Project description:Aims/hypothesisPrevious meta-analyses have suggested that diabetes confers a greater excess risk of coronary heart disease, stroke, vascular dementia, and heart failure in women compared to men. While the underlying mechanism that explains such greater excess risk is unknown, in the current meta-analysis we hypothesized that we would find a similar sex difference in the relationship between diabetes and peripheral arterial disease (PAD).MethodsPubMed MEDLINE, the Cochrane Database of Systematic Reviews, and Embase were systematically searched for prospective population-based cohort studies, with no restriction on publication date, language, or country. We included studies that reported the relative risk (RR), and its variability, for incident PAD associated with diabetes in both sexes. We excluded studies that did not adjust at least for age, and in which participants had pre-existing PAD. In cases where sex-specific results were not reported, study authors were contacted. Random-effects meta-analyses with inverse variance weighting were used to obtain summary sex-specific RRs and the women: men ratio of RRs for PAD. The Newcastle-Ottawa scale was used to assess study quality.ResultsData from seven cohorts, totalling 2071,260 participants (49.8% women), were included. The relative risk for incident PAD associated with diabetes compared with no diabetes was 1.96 (95% CI 1.29-2.63) in women and 1.84 (95% CI 1.29-2.86) in men, after adjusting for potential confounders. The multiple-adjusted RR ratio was 1.05 (95% CI 0.90-1.22), with virtually no heterogeneity between studies (I2 = 0%). All studies scored 6-8, on the Newcastle-Ottawa scale of 0-9, indicating good quality. Eleven of the 12 studies that met review inclusion criteria did not report sex-specific relative risk, and these data were collected through direct correspondence with the study authors.Conclusion/interpretationConsistent with other studies, we found evidence that diabetes is an independent risk factor for PAD. However, in contrast to similar studies of other types of cardiovascular disease, we did not find evidence that diabetes confers a greater excess risk in women compared to men for PAD. More research is needed to explain this sex differential between PAD and other forms of CVD, in the sequelae of diabetes. In addition, we found that very few studies reported the sex-specific relative risk for the association between diabetes and PAD, adding to existing evidence for the need for improved reporting of sex-disaggregated results in cardiovascular disease research.
Project description:BackgroundThis systematic review and meta-analysis assesses the association of arterial stiffness with age-related macular degeneration (AMD), glaucoma, retinal vein occlusion (RVO) and retinopathy (diabetic and hypertensive).MethodsMedline and Embase were systematically searched for observational studies of arterial stiffness and eye disease. Cohort studies were included if they estimated arterial stiffness using any measures based on the arterial waveform, with cross-sectional and case-control studies limited to measures of pulse wave velocity. We assessed the certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluation.ResultsThe systematic review of 61 studies (six for AMD, ten for glaucoma, six for RVO and 39 for retinopathy) showed that arterial stiffness overall was higher in people with eye disease than people without eye disease. Forty-four cross-sectional and case-control studies were included in the meta-analysis. Arterial stiffness estimated by way of pulse wave velocity was associated with AMD (mean difference: 0.92 m/s, 95% CI 0.37 to 1.46; 2 studies; n=381; low certainty evidence), glaucoma (mean difference: 0.97 m/s, 95% CI 0.31 to 1.64; 7 studies; n=3418; low certainty evidence), RVO (mean difference: 2.79 m/s, 95% CI 2.02 to 3.55; 5 studies; n=414; very low certainty evidence) and retinopathy (1.48 m/s, 95% CI 0.1.16 to 1.81; 22 studies; n=10 074; low certainty evidence). The 19 cohort studies identified (five for AMD, three for glaucoma, one for RVO and 10 for retinopathy) indicated overall that increased arterial stiffness was associated with the future development of eye disease.ConclusionsHigher arterial stiffness is associated with AMD, glaucoma, RVO and retinopathy PROSPERO REGISTRATION NUMBER: CRD42019129563.
Project description:BackgroundIt is unclear whether peripheral arterial cannulation is superior to central arterial cannulation for postcardiotomy veno-arterial extracorporeal membrane oxygenation (VA-ECMO).MethodsA systematic review was conducted using PubMed, Scopus, and Google Scholar to identify studies on postcardiotomy VA-ECMO for the present individual patient data (IPD) meta-analysis. Analysis was performed according to the intention-to-treat principle.ResultsThe investigators of 10 studies agreed to participate in the present IPD meta-analysis. Overall, 1269 patients were included in the analysis. Crude rates of in-hospital mortality after central versus peripheral arterial cannulation for VA-ECMO were 70.7% vs. 63.7%, respectively (adjusted OR 1.38, 95% CI 1.08-1.75). Propensity score matching yielded 538 pairs of patients with balanced baseline characteristics and operative variables. Among these matched cohorts, central arterial cannulation VA-ECMO was associated with significantly higher in-hospital mortality compared to peripheral arterial cannulation VA-ECMO (64.5% vs. 70.8%, p = 0.027). These findings were confirmed by aggregate data meta-analysis, which showed that central arterial cannulation was associated with an increased risk of in-hospital mortality compared to peripheral arterial cannulation (OR 1.35, 95% CI 1.04-1.76, I2 21%).ConclusionsAmong patients requiring postcardiotomy VA-ECMO, central arterial cannulation was associated with an increased risk of in-hospital mortality compared to peripheral arterial cannulation. This increased risk is of limited magnitude, and further studies are needed to confirm the present findings and to identify the mechanisms underlying the potential beneficial effects of peripheral VA-ECMO.
Project description:Background: Observational studies support an association between periodontitis (PD) and atherosclerotic vascular disease, but little is known specifically about peripheral arterial occlusive disease (PAOD). To systematically review the evidence for an association between PD and PAOD. Medline via PubMed. We searched the Pubmed database for original studies, case reports, case series, meta-analyses and systematic reviews that assessed whether there is an association between PD (all degrees of severity) and PAOD (all degrees of severity). The reporting of this systematic review was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement following the Population, Intervention, Control, and Outcome (PICO) format. 17 out of 755 detected studies were included in the qualitative synthesis. Nine studies demonstrated associations between PD and PAOD, and two studies reported associations between tooth loss and PAOD. Six studies addressed the pathomechanism regarding PD as a possible trigger for PAOD. No study that dismissed an association could be detected. Odds ratios or hazard ratios ranged from 1.3 to 3.9 in four large cohort studies after adjusting for established cardiovascular risk factors. The presented evidence supports a link between PD and PAOD. Further studies which address the temporality of PD and PAOD and randomized controlled intervention trials examining the causal impact of PD on PAOD are needed. Although our results cannot confirm a causal role of PD in the development of PAOD, it is likely that PD is associated with PAOD and plays a contributing role.