Helicobacter pylori eradication therapy for functional dyspepsia: Systematic review and meta-analysis

AIM: To evaluate whether Helicobacter pylori(H. pylori) eradication therapy benefits patients with functional dyspepsia(FD).METHODS: Randomized controlled trials(RCTs) investigating the efficacy and safety of H. pylori eradication therapy for patients with functional dyspepsia published in English(up to May 2015) were identified by searching Pub Med, EMBASE, and The Cochrane Library. Pooled estimates were measured using the fixed or random effect model. Overall effect was expressed as a pooled risk ratio(RR) or a standard mean difference(SMD). All data were analyzed with Review Manager 5.3 and Stata 12.0.RESULTS: This systematic review included 25 RCTs with a total of 5555 patients with FD. Twenty-three of these studies were used to evaluate the benefits of H. pylori eradication therapy for symptom improvement; the pooled RR was 1.23(95%CI: 1.12-1.36, P 0.0001). H. pylori eradication therapy demonstrated symptom improvement during long-term follow-up at ≥ 1 year(RR = 1.24; 95%CI: 1.12-1.37, P 0.0001) but not during short-term follow-up at 1 year(RR = 1.26; 95%CI: 0.83-1.92, P = 0.27). Seven studies showed no benefit of H. pylori eradication therapy on quality of life with an SMD of-0.01(95%CI:-0.11 to 0.08, P = 0.80). Six studies demonstrated that H. pylori eradication therapy reduced the development of peptic ulcer disease compared to no eradication therapy(RR = 0.35; 95%CI: 0.18-0.68, P = 0.002). Eight studies showed that H. pylori eradication therapy increased the likelihood of treatment-related side effects compared to no eradication therapy(RR = 2.02; 95%CI: 1.12-3.65, P = 0.02). Ten studies demonstrated that patients who received H. pylori eradication therapy were more likely to obtain histologic resolution of chronic gastritis compared to those who did not receive eradication therapy(RR = 7.13; 95%CI: 3.68-13.81, P 0.00001).CONCLUSION: The decision to eradicate H. pylori in patients with functional dyspepsia requires individual assessment.     

出血性转化对急性缺血性卒中患者转归的影响

Objective To investigate the effect of hemorrhagic transformation (HT) on the outcome of acute ischemic stroke.Methods One hundred and one patients with acute ischemic stroke were divided into cerebral infarction without HT,hemorrhagic infarction (HI),and parenchymal hematoma (PH) according to the CT and/or MRI findings.The modified Rankin Scale (mRS) was used to evaluate the outcome at 3 months after onset,and the good outcome was defined as mRS ≤ 2.The multivariate logistic regression analysis was used to identify the predictors of outcome in patients with acute ischemic stroke.Results There were 53 patients without HT,44 HI,and 4 PH,respectively in 101 patients with acute ischemic stroke.HI (OR =0.07,95% CI0.01-0.30;P ＜0.001),＜65 years (OR =52.94,95% CI9.12-307.27;P＜0.001),and NIHSS score ＜ 15 (OR= 0.63,95% CI 0.50-0.78;P＜0.001) were the independent predictors of good outcome for patients with acute ischemic stroke.Conclusions HI is one of the independent predictors of good outcome at 3 months after acute ischemic stroke.     

Who benefits from percutaneous closure of patent foramen ovale vs medical therapy for stroke prevention? In-depth and updated metaanalysis of randomized trials

BACKGROUND A few randomized clinical trials(RCT) and their meta-analyses have found patent foramen ovale closure(PFOC) to be beneficial in prevention of stroke compared to medical therapy. Whether the benefit is extended across all groups of patients remains unclear.AIM To evaluate the efficacy and safety of PFOC vs medical therapy in different groups of patients presenting with stroke, we performed this meta-analysis of RCTs.METHODS Electronic search of PubMed, EMBASE, Cochrane Central, CINAHL and ProQuest Central and manual search were performed from inception through September 2018 for RCTs. Ischemic stroke(IS), transient ischemic attack(TIA), a composite of IS, TIA and systemic embolism(SE), mortality, major bleeding,atrial fibrillation(AF) and procedural complications were the major outcomes.Random-effects model was used to perform analyses.RESULTS Meta-analysis of 6 RCTs including 3560 patients showed that the PFOC,compared to medical therapy reduced the risk of IS [odds ratio: 0.34; 95%confidence interval: 0.15-0.78; P = 0.01] and the composite of IS, TIA and SE [0.55(0.32-0.93); P = 0.02] and increased the AF risk [4.79(2.35-9.77); P 0.0001]. No statistical difference was observed in the risk of TIA [0.86(0.54-1.38); P = 0.54],mortality [0.74(0.28-1.93); P = 0.53] and major bleeding [0.81(0.42-1.56); P = 0.53]between two strategies. Subgroup analyses showed that compared to medical therapy, PFOC reduced the risk of stroke in persons who were males, ≤ 45 years of age and had large shunt or atrial septal aneurysm.CONCLUSION In certain groups of patients presenting with stroke, PFOC is beneficial in preventing future stroke compared to medical therapy.     

Patent foramen ovale closure reduces recurrent stroke risk in cryptogenic stroke:A systematic review and metaanalysis of randomized controlled trials

AIM To investigate if patent foramen ovale(PFO) closure device reduces the risk of recurrent stroke in patients with cryptogenic stroke.METHODS We searched five databases-Pub Med,EMBASE,Cochrane,CINAHL and Web-of-Science and clinicaltrials.gov from January 2000 to September 2017 for randomized trials comparing PFO closure to medical therapy in cryptogenic stroke.Heterogeneity was determined using Cochrane's Q statistics.Random effects model was used.RESULTS Five randomized controlled trials with 3440 patients were included in the analysis.Mean follow-up was 50 ± 20 mo.PFO closure was associated with a 41% reduction in incidence of recurrent strokes when compared to medical therapy alone in patients with cryptogenic stroke [risk ratio(RR): 0.59,95%CI: 0.40-0.87,P = 0.008].Atrial fibrillation was higher with device closure when compared to medical therapy alone(RR: 4.97,95%CI: 2.22-11.11,P 0.001).There was no difference between the two groups with respect to all-cause mortality,major bleeding or adverse events.CONCLUSION PFO device closure in appropriately selected patients with moderate to severe right-to-left shunt and/or atrial septal aneurysm shows benefit with respect to recurrent strokes,particularly in younger patients.Further studies are essential to evaluate the impact of higher incidence of atrial fibrillation seen with the PFO closure device on long-term mortality and stroke rates.     

Probiotics in Helicobacter pylori eradication therapy: A systematic review and meta-analysis

AIM: To summarize the evidence from randomized controlled trials(RCTs) regarding the effect of probiotics by using a meta-analytic approach.METHODS: In July 2013, we searched PubM ed, EMBASE, Ovid, the Cochrane Library, and three Chinese databases(Chinese Biomedical Literature Database, Chinese Medical Current Content, and Chinese Scientific Journals database) to identify relevant RCTs. We included RCTs investigating the effect of a combination of probiotics and standard therapy(probiotics group) with standard therapy alone(control group). Risk ratios(RRs) were used to measure the effect of probiotics plus standard therapy on Helicobacter pylori(H. pylori) eradication rates, adverse events, and patient compliance using a random-effect model. RESULTS: We included data on 6997 participants from 45 RCTs, the overall eradication rates of the probiotic group and the control group were 82.31% and 72.08%, respectively. We noted that the use of probiotics plus standard therapy was associated with an increased eradication rate by per-protocol set analysis(RR = 1.11; 95%CI: 1.08-1.15; P < 0.001) or intention-totreat analysis(RR = 1.13; 95%CI: 1.10-1.16; P < 0.001). Furthermore, the incidence of adverse events was 21.44% in the probiotics group and 36.27% in the control group, and it was found that the probiotics plus standard therapy significantly reduced the risk of adverse events(RR = 0.59; 95%CI: 0.48-0.71; P < 0.001), which demonstrated a favorable effect of probiotics in reducing adverse events associated with H. pylori eradication therapy. The specific reduction in adverse events ranged from 30% to 59%, and this reduction was statistically significant. Finally, probiotics plus standard therapy had little or no effect on patient compliance(RR = 0.98; 95%CI: 0.68-1.39; P = 0.889).CONCLUSION: The use of probiotics plus standard therapy was associated with an increase in the H. pylori eradication rate, and a reduction in adverse events resulting from treatment in the general population. However, this therapy did not improve patient compliance.     

Early nasogastric enteral nutrition for severe acute pancreatitis： A systematic review

AIM: To evaluate the effectiveness and safety of early nasogastric enteral nutrition (NGEN) for patients with severe acute pancreatitis (SAP). METHODS: We searched Cochrane Central Register of Controlled Trials (Issue 2, 2006), Pub-Medline (1966-2006), and references from relevant articles. We included randomized controlled trials (RCTs) only, which reported the mortality of SAP patients at least. Two reviewers assessed the quality of each trial and collected data independently. The Cochrane Collaboration’s RevMan 4.2.9 software was used for statistical analysis. RESULTS: Three RCTs were included, involving 131 patients. The baselines of each trial were comparable. Meta-analysis showed no significant differences in mortality rate of SAP patients between nasogastric and conventional routes (RR = 0.76, 95% CI = 0.37 and 1.55, P = 0.45), and in other outcomes, including time of hospital stay (weighted mean difference = -5.87, 95% CI = -20.58 and 8.84, P = 0.43), complication rate of infection (RR = 1.41, 95% CI = 0.62 and 3.23, P = 0.41) or multiple organ defi ciency syndrome (RR = 0.97, 95% CI = 0.27 and 3.47, P = 0.97), rate of admission to ICU (RR = 1.00, 95% CI = 0.48 and 2.09, P = 0.99) or conversion to surgery (RR = 0.66, 95% CI = 0.12 and 3.69, P = 0.64), as well as recurrence of re-feeding pain and adverse events associated with nutrition. CONCLUSION: Early NGEN is a breakthrough in the management of SAP. Based on current studies, early NGEN appears effective and safe. Since the available evidence is poor in quantity, it is hard to make an accurate evaluation of the role of early NGEN in SAP.Before recommendation to clinical practice, further high qualified, large scale, randomized controlled trials are needed.     

代谢综合征在缺血性卒中患者心脑血管事件发生中的作用

Objective To explore the association between metabolic syndrome (MS) and risk of cardiovascular disease events (CVD) in patients with ischemic stroke. Method A total of 1087 patients with ischemic stroke were enrolled from 5 community-based medical centres and underwent baseline evaluation on risk factors of stroke during the period of Jar. 2003 to Dec. 2006. After baseline survey, all patients were followed up until Dec 31, 2008 and new CVD events were recorded. MS was defined using CDS criteria. Proportional hazard models were used to assess the HRus and 95% CI of CVD events associated with MS and other components. Results The prevalence of MS was 40. 4% at baseline. During an average follow-up of 3.5 years, 178 patients developed new CVD events. After adjusted for age, gender, smoking,drinking, marriage status, education level, hospitalization, recurrence of stroke, stroke duration,depression, cognition impairment and ADL, MS remains the independent predictor for the risk of CVD events. Compared with patients with non-MS, the risk of CVD events increased by 44% (HR:1.44, 95%CI:1.06-1.95 ). The risk of CVD also increased with the number of MS components. Compared with patients with 1 or less than 1 components of MS, the risk of CVD events increased by 30% (HR:1. 30,95%CI:0.83-2.04) in those with 2 components and by 69% ( HR: 1.69,95% CI: 1.11-2.56) in those with 3or more components of MS. Hypertension and hyperglycemia and impaired fasting glucose also served as independent risk factors for CVD event ( all P ＜ 0. 001 ) . Conclusions MS was independently associated with increased risk of CVD events in patients with ischemic stroke. There was a dose-response relationship between the numbers of MS components and the risk of CVD event.     

颈动脉支架与内膜切除术治疗颈动脉狭窄疗效和安全性的Meta分析

目的 系统评价颈动脉支架(carotid artery stenting,CAS)和颈动脉内膜切除术(carotid endarterectomy,CEA)治疗颈动脉狭窄的安全性和疗效.方法 计算机检索PubMed、EMbase、Cochrane图书馆临床对照试验资料库、中国期刊全文数据库(CNKI)、中文科技期刊数据库(VIP)以及万方医学数据库,并辅以手工检索,收集CAS和CEA治疗颈动脉狭窄的随机对照试验,采用Cochrane协作网提供的RevMan 5.0.24软件进行Meta分析.结果 共纳入12个研究,6903例患者,其中CAS组3460例,CEA组3443例.CAS组术后30 d脑卒中或死亡联合发生风险(RR=1.64,95%CI:1.33～2.03,P＜0.00001)以及脑卒中风险(RR=1.70,95%CI:1.34～2.14,P＜0.00001)高于CEA组;CEA组术后30 d心肌梗死风险(RR=0.62,95%CI:0.39～0.97,P=0.04)和颅神经损伤风险(RR=0.07,95%CI:0.03～0.16,P＜0.00001)高于CAS组;两组术后30 d死亡风险(RR=1.33,95%CI:0.78～2.28,P=0.29)、致残性脑卒中风险(RR=1.27,95%CI:0.82～1.96,P=0.29)和术后1年脑卒中或死亡联合发生风险(RR=0.96,95%CI:0.63～1.46,P=0.84)差异无统计学意义.结论 从安全性方面考虑,对于一般手术风险的颈动脉狭窄患者,CEA仍是治疗颈动脉狭窄的首选治疗手段.具有手术高危因素或不适合手术的患者,CAS治疗更具有优势.

Abstract：

Objective To compare the safety and efficacy of carotid artery stenting (CAS) and carotid endarterectomy(CEA) for the treatment of carotid stenosis. Methods The electronic databases (PubMed, EMbase, Cochrane Central Register of Controlled Trials, CNKI, VIP and Wanfang) were searched in order to retrieve randomized controlled trials (RCTs) about comparing CAS and CEA for the treatment of carotid stenosis. Cochrane collaboration's RevMan 5.0.24 were used for analyzing data. Results Twelve RCTs totalling 6903 patients (3460 patients were randomized to CAS and 3443 randomized to CEA) with symptomatic or asymptomatic stenosis were included in the meta-analysis. There were significantly higher 30-day relative risks after CAS than after CEA for death or any stroke [RR=1.64, 95%CI (1.33-2.03), P＜0.00001] and for stroke [RR=1.70, 95%CI (1.34-2.14), P＜0.00001]. The relative risks of myocardial infarction [RR=0.62, 95%CI (0.39-0.97), P=0.04] and cranial neuropathy [RR=0.07, 95%CI (0.03-0.16), P＜0.00001] was significantly less after CAS than after CEA. The relative risks of death [RR=1.27, 95%CI (0.82-1.96), P=0.29] or disabling stroke within 30 days [RR=1.33, 95%CI (0.78-2.28), P=0.29] and any stroke or death at 1 year after the procedures [RR=0.96, 95%CI (0.63-1.46), P=0.84] did not differ significantly between CAS and CEA operation. Conclusions CEA remains the first choice for treatment of carotid stenosis for patients with low surgery risk. For patients with high surgery risk and unsuitable for surgery, CAS has more advantages. It is reasonable to view CAS and CEA as complementary rather than competing modes of therapy.     

Extended antimicrobial prophylaxis after gastric cancer surgery: A systematic review and meta-analysis

AIM: To investigate the efficacy of extended antimicrobial prophylaxis (EAP) after gastrectomy by systematic review of literature and meta-analysis. METHODS: Electronic databases of PubMed, Embase, CINAHL, the Cochrane Database of Systematic Reviews, the Cochrane Controlled Trials Register and the China National Knowledge Infrastructure were searched systematically from January 1980 to October 2012. Strict literature retrieval and data extraction were carried out independently by two reviewers and meta-analyses were conducted using RevMan 5.0.2 with statistics tools risk ratios (RRs) and intention-to-treat analyses to evaluate the items of total complications, surgical site infection, incision infection, organ (or space) infection, remote site infection, anastomotic leakage (or dehiscence) and mortality. Fixed model or random model was selected accordingly and forest plot was conducted to display RR. Likewise, Cochrane Risk of Bias Tool was applied to evaluate the quality of randomized controlled trials (RCTs) included in this meta-analysis. RESULTS: A total of 1095 patients with gastric cancer were enrolled in four RCTs. No statistically significant differences were detected between EAP and intraoperative antimicrobial prophylaxis (IAP) in total complications (RR of 0.86, 95%CI: 0.63-1.16, P = 0.32), surgical site infection (RR of 1.97, 95%CI: 0.86-4.48, P = 0.11), incision infection (RR of 4.92, 95%CI: 0.58-41.66, P = 0.14), organ or space infection (RR of 1.55, 95%CI: 0.61-3.89, P = 0.36), anastomotic leakage or dehiscence (RR of 3.85, 95%CI: 0.64-23.17, P = 0.14) and mortality (RR of 1.14, 95%CI: 0.10-13.12; P = 0.92). Likewise, multiple-dose antimicrobial prophylaxis showed no difference compared with single-dose antimicrobial prophylaxis in surgical site infection (RR of 1.10, 95%CI: 0.62-1.93, P = 0.75). Nevertheless, EAP showed a decreased remote site infection rate compared with IAP alone (RR of 0.54, 95%CI: 0.34-0.86, P = 0.01), which is the only significant finding. Unfortunately, EAP did not decrease     

Single-incision laparoscopic appendectomy vs conventional laparoscopic appendectomy:Systematic review and meta-analysis

AIM: To assess the differences in clinical benefits and disadvantages of single-incision laparoscopic appendectomy(SILA) and conventional laparoscopic appendectomy(CLA).METHODS: The Cochrane Library,MEDLINE,Embase,Science Citation Index Expanded,and Chinese Biomedical Literature Database were electronically searched up through January 2013 to identify randomized controlled trails(RCTs) comparing SILA with CLA.Data was extracted from eligible studies to evaluate the pooled outcome effects for the total of 1068 patients.The meta-analysis was performed using Review Manager 5.2.0.For dichotomous data and continuous data,the risk ratio(RR) and the mean difference(MD) were calculated,respectively,with 95%CI for both.For continuous outcomes with different measurement scales in different RCTs,the standardized mean difference(SMD) was calculated with 95%CI.Sensitivity and subgroup analyses were performed when necessary.RESULTS: Six RCTs were identified that compared SILA(n = 535) with CLA(n = 533).Five RCTs had a high risk of bias and one RCT had a low risk of bias.SILA was associated with longer operative time(MD = 5.68,95%CI: 3.91-7.46,P < 0.00001),higher conversion rate(RR = 5.14,95%CI: 1.25-21.10,P = 0.03) and better cosmetic satisfaction score(MD = 0.52,95%CI: 0.30-0.73,P < 0.00001) compared with CLA.No significant differences were found for total complications(RR = 1.15,95%CI: 0.76-1.75,P = 0.51),drain insertion(RR = 0.72,95%CI: 0.41-1.25,P = 0.24),or length of hospital stay(SMD = 0.04,95%CI:-0.08-0.16,P = 0.57).Because there was not enough data among the analyzed RCTs,postoperative pain was not calculated.CONCLUSION: The benefit of SILA is cosmetic satisfaction,while the disadvantages of SILA are longer operative time and higher conversion rate.     

Ticagrelor versus clopidogrel after fibrinolytic therapy in patients with ST-elevation myocardial infarction: a systematic review and meta-analysis of randomized clinical trials

Dual antiplatelet therapy with aspirin and clopidogrel are recommended as adjuncts to fibrinolytic-treated patients with ST-elevation myocardial infarction (STEMI). However, the role of switching to ticagrelor within 24 h of fibrinolytics compared with clopidogrel continuation in this setting is uncertain. Hence, we conducted a comprehensive search of electronic databases for all randomized clinical trials (RCTs) that evaluated the safety and efficacy of ticagrelor versus clopidogrel after fibrinolytic therapy in patients with STEMI. A random-effects model was used to calculate the risk ratios (RRs) and 95% confidence intervals (CIs). A total of 5 RCTs that evaluated the efficacy of ticagrelor post-fibrinolysis were identified. We included 3 RCTs with 3999 total patients for our meta-analysis. The results showed similar short-term clinical outcomes between ticagrelor and clopidogrel with regard to rates of Bleeding Academic Research Consortium (BARC) type?≥?2 bleeding (RR 0.94; 95% CI 0.56–1.60; P?=?0.83), major adverse cardiovascular events (RR 0.87; 95% CI 0.49–1.52; P?=?0.62), mortality (RR 0.92; 95% CI 0.53–1.59; P?=?0.77), myocardial infarction (RR 0.76; 95% CI 0.43–1.36; P?=?0.36), and stroke (RR 0.93; 95% CI 0.50–1.73; P?=?0.82). Our results demonstrate that in STEMI patients treated with fibrinolytic therapy, switching to ticagrelor was associated with similar bleeding and ischemic outcomes compared with clopidogrel continuation.     

Meta-analysis of efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus warfarin in patients with atrial fibrillation

New oral anticoagulants, including apixaban, dabigatran, and rivaroxaban, have been developed as alternatives to warfarin, the standard oral anticoagulation therapy for patients with atrial fibrillation (AF). A systematic review and meta-analysis of randomized controlled trials was performed to compare the efficacy and safety of new oral anticoagulants to those of warfarin in patients with AF. The published research was systematically searched for randomized controlled trials of >1 year in duration that compared new oral anticoagulants to warfarin in patients with AF. Random-effects models were used to pool efficacy and safety data across randomized controlled trials. Three studies, including 44,563 patients, were identified. Patients randomized to new oral anticoagulants had a decreased risk for all-cause stroke and systemic embolism (relative risk [RR] 0.78, 95% confidence interval [CI] 0.67 to 0.92), ischemic and unidentified stroke (RR 0.87, 95% CI 0.77 to 0.99), hemorrhagic stroke (RR 0.45, 95% CI 0.31 to 0.68), all-cause mortality (RR 0.88, 95% CI 0.82 to 0.95), and vascular mortality (RR 0.87, 95% CI 0.77 to 0.98). Randomization to a new oral anticoagulant was associated with a lower risk for intracranial bleeding (RR 0.49, 95% CI 0.36 to 0.66). Data regarding the risks for major bleeding (RR 0.88, 95% CI 0.71 to 1.09) and gastrointestinal bleeding (RR 1.25, 95% CI 0.91 to 1.72) were inconclusive. In conclusion, the new oral anticoagulants are more efficacious than warfarin for the prevention of stroke and systemic embolism in patients with AF. With a decreased risk for intracranial bleeding, they appear to have a favorable safety profile, making them promising alternatives to warfarin.     

Meta-Analysis of Secondary Prevention of Cryptogenic Stroke

BackgroundCryptogenic stroke and embolic stroke of undetermined source (ESUS) are a frequently encountered categories of ischemic stroke with an uncertain cause.MethodsWe analyzed all randomized clinical trials (RCTs) that evaluated antithrombotic therapy and patent foramen ovale (PFO) closure in cryptogenic stroke and/or ESUS. We calculated aggregate hazard ratios (HRs) using direct and network meta-analysis. The primary outcome was recurrent ischemic stroke.ResultsTen RCTs with a total of 16,876 patients, randomizing 32,143 patient-years of follow-up (mean age 61.2 ± 13.5 with 39.2% female) were identified. Anticoagulation therapy was associated with significantly reduced recurrent ischemic stroke compared with antiplatelet therapy (HR = 0.66; [95% confidence interval (CI) = 0.47–0.94]). Meta-regression analysis showed significantly reduced recurrent stroke with longer duration of therapy, and significantly increased events with advanced age. Significant interactions were observed based on the presence of PFO, stroke type, and anticoagulant used. There were no significant differences with regard to the composite ischemic outcome, transient ischemic attack, any death, major bleeding, or intracranial bleeding. In the network meta-analysis, compared to antiplatelet therapy, warfarin (HR = 0.31; [95% credible interval (CrI) = 0.12–0.68]) and PFO closure (HR = 0.14; 95% CrI = 0.05–0.31]) were associated with significantly reduced recurrent ischemic stroke. In rank order, PFO closure was associated with the best outcome, followed by warfarin.ConclusionsAmong patients with cryptogenic stroke, anticoagulation therapy, as compared with antiplatelet therapy is associated with lower rate of recurrent stroke. The small sample size and high heterogeneity with regards to bleeding outcomes require further large trials. In patients with PFO, closure and warfarin are associated with the lowest rates of recurrent stroke.     

P2Y12 Inhibitors versus Aspirin Monotherapy for Long-term Secondary Prevention of Atherosclerotic Cardiovascular Disease Events: A Systematic Review and Meta-analysis

Patients with established atherosclerotic cardiovascular disease (ASCVD) need long-term antiplatelet therapy to decrease the risk of future ASCVD events. We searched PubMed, Cochrane Library, and ClinicalTrials.gov (inception through September 2021) for randomized controlled trials (RCTs) evaluating P2Y₁₂ inhibitors vs aspirin for secondary prevention of ASCVD events. Seven RCTs including a total of 56,982 patients were included in this analysis. The median follow-up duration was 22.8 (IQR 12) months. When P2Y₁₂ inhibitors were compared with aspirin as long-term antiplatelet therapy for secondary prevention of ASCVD events, there was a significant decrease in the risk of myocardial infarction [RR: 0.83; 95% CI: 0.72-0.94], and stroke [RR: 0.90; 95% CI: 0.83-0.99]. However, there was no significant difference in all-cause mortality [RR: 1.02; 95% CI: 0.92-1.12], or cardiovascular mortality [RR: 0.95; 95% CI: 0.83-1.08] between P2Y₁₂ inhibitors and aspirin users. Additionally, there was no significant difference in major bleeding events [RR: 0.88; 95% CI: 0.74-1.04], or all bleeding events [RR: 1.09; 95% CI: 0.90-1.33] between P2Y₁₂ inhibitors and aspirin groups. Use of P2Y₁₂ inhibitor monotherapy is associated with lower rates of myocardial infarction and stroke in ASCVD patients without any significant difference in mortality, or bleeding compared to aspirin monotherapy.     

Direct Oral Anticoagulant Versus Warfarin After Left Atrial Appendage Closure With WATCHMAN: Updated Systematic Review and Meta-analysis

In the pivotal WATCHMAN trials, warfarin was used for post-procedural anticoagulation in the first 45 days after left atrial appendage closure. We aimed to investigate the efficacy and safety of direct oral anticoagulant (DOAC) versus warfarin after WATCHMAN. We performed a literature search of 5 electronic databases to identify studies comparing DOAC with warfarin after WATCHMAN. We pooled outcomes for the efficacy (thromboembolism, device-related thrombus [DRT], peridevice leak [PDL] >5 mm) and safety endpoints (bleeding, mortality). Thromboembolism was defined as ischemic stroke, transient ischemic attack, or systemic embolism. We included 10 cohort studies with 2,440 patients, of whom 1,397 (57.3%) received DOAC. Concerning periprocedural outcomes (within 7 days following implantation), DOAC was associated with a reduction in major bleeding (Risk ratio [RR] 0.32; 95% confidence interval [CI] 0.11-0.92) compared with warfarin, without significant differences in all bleeding (RR 0.46; 95% CI 0.15-1.42) and thromboembolism (RR 0.93; 95% CI 0.21-4.16). On first follow-up transesophageal echocardiography, DRT (RR 0.79; 95% CI 0.39-1.60) and PDL>5 mm (RR 0.44; 95% CI 0.16-1.20) were comparable among groups. With a mean follow-up of 1.5-12 months, DOAC was associated with reductions in major bleeding (RR 0.52; 95% CI 0.30-0.89) and all bleeding (RR 0.38; 95% CI 0.25-0.58) compared with warfarin. The outcomes of thromboembolism (RR 0.79; 95% CI 0.36-1.73) and all-cause mortality (RR 0.49; 95% CI 0.19-1.28) were not significantly different between the 2 groups. Following WATCHMAN implantation, DOAC was associated with reductions in major bleeding and all bleeding compared with warfarin at mid-term follow-up. The outcomes of thromboembolism, all-cause mortality, DRT, and PDL >5 mm were comparable among groups.     

Meta-Analysis of Efficacy and Safety of Proton Pump Inhibitors with Dual Antiplatelet Therapy for Coronary Artery Disease

BackgroundThere is inconsistency in the literature regarding the clinical effects of proton pump inhibitors (PPI) when added to dual antiplatelet therapy (DAPT) in subjects with coronary artery disease (CAD). We performed meta-analysis stratified by study design to explore these differences.Methods and results39 studies [4 randomized controlled trials (RCTs) and 35 observational studies) were selected using MEDLINE, EMBASE and CENTRAL (Inception-January 2018). In 221,204 patients (PPI = 77,731 patients, no PPI =143,473 patients), RCTs restricted analysis showed that PPI did not increase the risk of all-cause mortality (Risk Ratio (RR): 1.35, 95% Confidence Interval (CI), 0.56–3.23, P = 0.50, I² = 0), cardiovascular mortality (RR: 0.94, 95% CI, 0.25–3.54, P = 0.92, I² = 56), myocardial infarction (MI) (RR: 0.97, 95% CI, 0.62–1.51, P = 0.88, I² = 0) or stroke (RR: 1.11, 95% CI, 0.25–5.04, P = 0.89, I² = 26). However, PPI significantly reduced the risk of gastrointestinal (GI) bleeding (RR: 0.32, 95% CI, 0.20–0.52, P < 0.001, I² = 0). Conversely, analysis of observational studies showed that PPI significantly increased the risk of all-cause mortality (RR: 1.25, 95% CI, 1.11–1.41, P < 0.001, I² = 82), cardiovascular mortality (RR: 1.25, 95% CI, 1.03–1.52, P = 0.02, I² = 71), MI (RR: 1.30, 95% CI, 1.16–1.47, P < 0.001, I² = 82) and stroke (RR: 1.60, 95% CI, 1.43–1.78, P < 0.001, I² = 0), without reducing GI bleeding (RR: 0.74, 95% CI, 0.45–1.22, P = 0.24, I² = 79).ConclusionMeta-analysis of RCTs endorsed the use of PPI with DAPT for reducing GI bleeding without worsening cardiovascular outcomes. These findings oppose the negative observational data regarding effects of PPI with DAPT.     

Efficacy and Safety of the Non-Vitamin K Antagonist Oral Anticoagulant Among Patients With Nonvalvular Atrial Fibrillation and Cancer: A Systematic Review and Network Meta-analysis

Patients with cancer are at higher risk of atrial fibrillation (AF). Currently there are no definitive data on clinical outcomes for nonvitamin K antagonist oral anticoagulant (NOACs) and warfarin in cancer patients with AF. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of NOACs compared with warfarin. A search through Pubmed/MEDLINE, Embase, and Cochrane library was done from the databases inception to March 2022. Studies that compared NOACs to warfarin in the setting of AF and cancer were included. The primary outcomes were the incidence of major bleeding and ischemic stroke/systemic embolism (SE). Secondary outcomes were major adverse cardiovascular event (MACE), intracranial bleeding, and Major gastrointestinal bleeding. Risk ratios (RRs) with 95% confidence intervals (CI) were used to report the outcomes. A total of 11 studies were included. We found that NOACs were associated with a lower incidence of major bleeding and combined ischemic stroke/SE in patients with AF and cancer compared with warfarin (RR 0.57; 95% CI 0.44-0.75, P < 0.0001 and RR 0.59; 95% CI 0.47-0.75, P < 0.0001, respectively). Also, there was lower incidence of Intracranial and major gastrointestinal bleeding in patients who received NOACs compared with warfarin (P < 0.0001). Network analyses revealed that apixaban and dabigatran were associated with reduction of major bleeding compared with warfarin. Among patients who diagnosed with AF and cancer, NOACs were associated with lower incidence of major bleeding ischemic stroke/SE compared with warfarin. Furthermore, NOACs were associated with lower gastrointestinal and intracranial bleeding.     

Secondary prevention of cryptogenic stroke in patients with patent foramen ovale: a systematic review and meta-analysis

The aim of our study is to compare patent foramen ovale (PFO) closure versus medical treatment and antiplatelet versus anticoagulant therapy in patients with cryptogenic stroke (CS) and PFO. We conducted a systematic review and meta-analysis with trial sequential analysis (TSA) of randomized trials. Primary outcomes are stroke or transient ischemic attack (TIA) and all-cause mortality. Secondary outcomes are peripheral embolism, bleeding, serious adverse events, myocardial infarction and atrial dysrhythmias. We performed an intention to treat meta-analysis with a random-effects model. We include six trials (3677 patients, mean age 47.3 years, 55.8% men). PFO closure is associated with a lower recurrence of stroke or TIA at a mean follow-up of 3.88 years compared to medical therapy [risk ratio (RR) 0.55, 95% CI 0.38–0.81; I²?=?40%]. The TSA confirms this result. No difference is found in mortality (RR 0.74, 95% CI 0.35–1.60; I²?=?0%), while PFO closure is associated with a higher incidence of atrial dysrhythmias (RR 4.55, 95% CI 2.16–9.60; I²?=?25%). The rate of the other outcomes is not different among the two groups. The comparison between anticoagulant and antiplatelet therapy shows no difference in terms of stroke recurrence, mortality and bleeding. There is conclusive evidence that PFO closure reduces the recurrence of stroke or TIA in patients younger than 60 years of age with CS. More data are warranted to assess the consequences of the increase in atrial dysrhythmias and the advantage of PFO closure over anticoagulants.     

Routine Invasive Strategy in Elderly Patients with Non-ST Elevation Acute Coronary Syndrome: An Updated Systematic Review and Meta-analysis of Randomized Trials

Invasive treatment with coronary angiography is preferred approach for patients with non-ST elevation acute coronary syndrome (NSTE-ACS) compared to medical therapy alone. The results from the randomized clinical trials (RCT) that compared the invasive treatment strategy vs. conservative approach in the elderly (≥75 years) with NSTE-ACS has been inconsistent. To compare invasive and conservative strategies in the elderly (>75 years) with NSTE-ACS. We searched PubMed, Cochrane CENTRAL Register and ClinicalTrials.gov (inception through July 10, 2021) for RCTs comparing invasive and conservative strategies in the elderly with NSTE-ACS. We used random-effects model to calculate risk ratio (RR) with 95% confidence interval(CI). A total of 6 RCT including 2,323 patients were included in the meta-analysis. The median follow-up duration was 13.5 months. When invasive approach was compared to conservative strategy, it showed no difference in all-cause mortality in patients aged ≥75 years with NSTE-ACS (RR of 0.85; 95% CI 0.70–1.04; P = 0.12; I2 = 0%). There was significant reduction in MI (RR 0.59; 95% CI 0.49 0.71; P < 0.001; I2 = 0%) and unplanned revascularization (RR 0.30, 95% CI 0.17-0.53, P <0.001, I2 = 0%). Invasive strategy was associated with higher risk of major bleeding when compared to conservative treatment (RR 2.12, 95% CI 1.21-3.74, P = 0.009, I2 = 0%). Comparison of both strategies showed no significant difference in stroke (RR 0.75; 95% CI 0.38-1.46, P = 0.40; I2 = 0%). This updated meta-analysis suggests that in elderly patients (>75 years) with NSTE-ACS, a routine invasive strategy is associated with a reduction in MI and revascularization, while increasing the risk of major bleeding, but without difference in all-cause mortality and stroke.     

The impact of warfarin use on clinical outcomes in atrial fibrillation: a population-based study

BACKGROUND: Atrial fibrillation (AF) is the most common adult arrhythmia, and significantly increases the risk of ischemic stroke. Oral anticoagulation may be underused and may be less effective in community settings than clinical trial settings. OBJECTIVES: To determine the rates of thromboembolism and bleeding in an ambulatory cohort of patients with AF. METHODS: Observational study of Nova Scotian residents with AF identified by electrocardiogram in ambulatory settings between November 1999 and January 2001. Main outcome measures were rates of thromboembolism and bleeding over two years. RESULTS: Four hundred twenty-five patients were included in the study. The mean (+/-SD) age was 70.6+/-11.1 years, and 40% were women. Warfarin therapy was used by 68% of patients. Sixty-two per cent of patients had hypertension, 21% had a previous stroke or transient ischemic attack, 44% had congestive heart failure and 20% were diabetic. The overall rate of thromboembolic events was 2.7% in warfarin users and 8.5% in nonwarfarin users over two years, with an RR reduction of 68% (OR 0.31, 95% CI 0.09 to 0.91; P=0.047). The annual rate of ischemic stroke was 1.2% and 3.1% in warfarin and nonwarfarin users, respectively, with an RR reduction of 62% (OR 0.29, 95% CI 0.08 to 1.04; P=0.057). The overall rate of major bleeding was 2.6% in warfarin users and 1.4% in nonwarfarin users (P=0.667). The annual mortality rate was 7.79% in warfarin users and 9.93% in nonwarfarin users (P=0.192). CONCLUSIONS: Warfarin use was found to significantly reduce the rate of thromboembolic events without a concomitant increase in hemorrhagic events. The present study confirms the effectiveness of warfarin therapy in a population-based cohort.