Transcatheter aortic valve implantation vs. surgical aortic valve replacement for treatment of severe aortic stenosis: a meta-analysis of randomized trials. Siontis George C M,Praz Fabien,Pilgrim Thomas,Mavridis Dimitris,Verma Subodh,Salanti Georgia,Søndergaard Lars,Jüni Peter,Windecker Stephan European heart journal AIMS:In view of the currently available evidence from randomized trials, we aimed to compare the collective safety and efficacy of transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) across the spectrum of risk and in important subgroups. METHODS AND RESULTS:Trials comparing TAVI vs. SAVR were identified through Medline, Embase, and Cochrane databases. The primary outcome was death from any cause at 2 years. We performed random-effects meta-analyses to combine the available evidence and to evaluate the effect in different subgroups. This systematic review and meta-analysis is registered with PROSPERO (CRD42016037273). We identified four eligible trials including 3806 participants, who were randomly assigned to undergo TAVI (n = 1898) or SAVR (n = 1908). For the primary outcome of death from any cause, TAVI when compared with SAVR was associated with a significant 13% relative risk reduction [hazard ratio (95% CI): 0.87 (0.76-0.99); P = 0.038] with homogeneity across all trials irrespective of TAVI device (P = 0.306) and baseline risk (P = 0.610). In subgroup analyses, TAVI showed a robust survival benefit over SAVR for patients undergoing transfemoral access [0.80 (0.69-0.93); P = 0.004], but not transthoracic access [1.17 (0.88-1.56); P = 0.293] (P = 0.024) and in female [0.68 (0.50-0.91); P = 0.010], but not male patients [0.99 (0.77-1.28); P = 0.952] (P = 0.050). Secondary outcomes of kidney injury, new-onset atrial fibrillation, and major bleeding favoured TAVI, while major vascular complications, incidence of permanent pacemaker implantation, and paravalvular regurgitation favoured SAVR. CONCLUSION:Compared with SAVR, TAVI is associated with a significant survival benefit throughout 2 years of follow-up. Importantly, this superiority is observed irrespective of the TAVI device across the spectrum of intermediate and high-risk patients, and is particularly pronounced among patients undergoing transfemoral TAVI and in females. 10.1093/eurheartj/ehw225
    Catheter Ablation of Atrial Fibrillation in Patients With Heart Failure: A Meta-analysis of Randomized Controlled Trials. Turagam Mohit K,Garg Jalaj,Whang William,Sartori Samantha,Koruth Jacob S,Miller Marc A,Langan Noelle,Sofi Aamir,Gomes Anthony,Choudry Subbarao,Dukkipati Srinivas R,Reddy Vivek Y Annals of internal medicine This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background:Atrial fibrillation (AF) and heart failure (HF) frequently coexist and are associated with increased morbidity and mortality risk. Purpose:To compare benefits and harms between catheter ablation and drug therapy in adult patients with AF and HF. Data Sources:ClinicalTrials.gov, PubMed, Web of Science (Clarivate Analytics), EBSCO Information Services, Cochrane Central Register of Controlled Trials, Google Scholar, and various scientific conference sessions from 1 January 2005 to 1 October 2018. Study Selection:Randomized controlled trials (RCTs) published in English that had at least 6 months of follow-up and compared clinical outcomes of catheter ablation versus drug therapy in adults with AF and HF. Data Extraction:2 investigators independently extracted data and assessed study quality. Data Synthesis:6 RCTs involving 775 patients met inclusion criteria. Compared with drug therapy, AF ablation reduced all-cause mortality (9.0% vs. 17.6%; risk ratio [RR], 0.52 [95% CI, 0.33 to 0.81]) and HF hospitalizations (16.4% vs. 27.6%; RR, 0.60 [CI, 0.39 to 0.93]). Ablation improved left ventricular ejection fraction (LVEF) (mean difference, 6.95% [CI, 3.0% to 10.9%]), 6-minute walk test distance (mean difference, 20.93 m [CI, 5.91 to 35.95 m]), peak oxygen consumption (Vo2max) (mean difference, 3.17 mL/kg per minute [CI, 1.26 to 5.07 mL/kg per minute]), and quality of life (mean difference in Minnesota Living with Heart Failure Questionnaire score, -9.02 points [CI, -19.75 to 1.71 points]). Serious adverse events were more common in the ablation groups, although differences between the ablation and drug therapy groups were not statistically significant (7.2% vs. 3.8%; RR, 1.68 [CI, 0.58 to 4.85]). Limitation:Results driven primarily by 1 clinical trial, possible patient selection bias in the ablation group, lack of patient-level data, open-label trial designs, and heterogeneous follow-up length among trials. Conclusion:Catheter ablation was superior to conventional drug therapy in improving all-cause mortality, HF hospitalizations, LVEF, 6-minute walk test distance, Vo2max, and quality of life, with no statistically significant increase in serious adverse events. Primary Funding Source:None. 10.7326/M18-0992
    Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study. Lipnicki Darren M,Makkar Steve R,Crawford John D,Thalamuthu Anbupalam,Kochan Nicole A,Lima-Costa Maria Fernanda,Castro-Costa Erico,Ferri Cleusa Pinheiro,Brayne Carol,Stephan Blossom,Llibre-Rodriguez Juan J,Llibre-Guerra Jorge J,Valhuerdi-Cepero Adolfo J,Lipton Richard B,Katz Mindy J,Derby Carol A,Ritchie Karen,Ancelin Marie-Laure,Carrière Isabelle,Scarmeas Nikolaos,Yannakoulia Mary,Hadjigeorgiou Georgios M,Lam Linda,Chan Wai-Chi,Fung Ada,Guaita Antonio,Vaccaro Roberta,Davin Annalisa,Kim Ki Woong,Han Ji Won,Suh Seung Wan,Riedel-Heller Steffi G,Roehr Susanne,Pabst Alexander,van Boxtel Martin,Köhler Sebastian,Deckers Kay,Ganguli Mary,Jacobsen Erin P,Hughes Tiffany F,Anstey Kaarin J,Cherbuin Nicolas,Haan Mary N,Aiello Allison E,Dang Kristina,Kumagai Shuzo,Chen Tao,Narazaki Kenji,Ng Tze Pin,Gao Qi,Nyunt Ma Shwe Zin,Scazufca Marcia,Brodaty Henry,Numbers Katya,Trollor Julian N,Meguro Kenichi,Yamaguchi Satoshi,Ishii Hiroshi,Lobo Antonio,Lopez-Anton Raul,Santabárbara Javier,Leung Yvonne,Lo Jessica W,Popovic Gordana,Sachdev Perminder S, PLoS medicine BACKGROUND:With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. METHODS AND FINDINGS:We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. CONCLUSIONS:These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences. 10.1371/journal.pmed.1002853
    Benefits and Harms of Oral Anticoagulant Therapy in Chronic Kidney Disease: A Systematic Review and Meta-analysis. Ha Jeffrey T,Neuen Brendon L,Cheng Lap P,Jun Min,Toyama Tadashi,Gallagher Martin P,Jardine Meg J,Sood Manish M,Garg Amit X,Palmer Suetonia C,Mark Patrick B,Wheeler David C,Jha Vivekanand,Freedman Ben,Johnson David W,Perkovic Vlado,Badve Sunil V Annals of internal medicine Background:Effects of oral anticoagulation in chronic kidney disease (CKD) are uncertain. Purpose:To evaluate the benefits and harms of vitamin K antagonists (VKAs) and non-vitamin K oral anticoagulants (NOACs) in adults with CKD stages 3 to 5, including those with dialysis-dependent end-stage kidney disease (ESKD). Data Sources:English-language searches of MEDLINE, EMBASE, and Cochrane databases (inception to February 2019); review bibliographies; and ClinicalTrials.gov (25 February 2019). Study Selection:Randomized controlled trials evaluating VKAs or NOACs for any indication in patients with CKD that reported efficacy or bleeding outcomes. Data Extraction:Two authors independently extracted data, assessed risk of bias, and rated certainty of evidence. Data Synthesis:Forty-five trials involving 34 082 participants who received anticoagulation for atrial fibrillation (AF) (11 trials), venous thromboembolism (VTE) (11 trials), thromboprophylaxis (6 trials), prevention of dialysis access thrombosis (8 trials), and cardiovascular disease other than AF (9 trials) were included. All but the 8 trials involving patients with ESKD excluded participants with creatinine clearance less than 20 mL/min or estimated glomerular filtration rate less than 15 mL/min/1.73 m2. In AF, compared with VKAs, NOACs reduced risks for stroke or systemic embolism (risk ratio [RR], 0.79 [95% CI, 0.66 to 0.93]; high-certainty evidence) and hemorrhagic stroke (RR, 0.48 [CI, 0.30 to 0.76]; moderate-certainty evidence). Compared with VKAs, the effects of NOACs on recurrent VTE or VTE-related death were uncertain (RR, 0.72 [CI, 0.44 to 1.17]; low-certainty evidence). In all trials combined, NOACs seemingly reduced major bleeding risk compared with VKAs (RR, 0.75 [CI, 0.56 to 1.01]; low-certainty evidence). Limitation:Scant evidence for advanced CKD or ESKD; data mostly from subgroups of large trials. Conclusion:In early-stage CKD, NOACs had a benefit-risk profile superior to that of VKAs. For advanced CKD or ESKD, there was insufficient evidence to establish benefits or harms of VKAs or NOACs. Primary Funding Source:None. (PROSPERO: CRD42017079709). 10.7326/M19-0087
    Estimated stroke risk, yield, and number needed to screen for atrial fibrillation detected through single time screening: a multicountry patient-level meta-analysis of 141,220 screened individuals. Lowres Nicole,Olivier Jake,Chao Tze-Fan,Chen Shih-Ann,Chen Yi,Diederichsen Axel,Fitzmaurice David A,Gomez-Doblas Juan Jose,Harbison Joseph,Healey Jeff S,Hobbs F D Richard,Kaasenbrood Femke,Keen William,Lee Vivian W,Lindholt Jes S,Lip Gregory Y H,Mairesse Georges H,Mant Jonathan,Martin Julie W,Martín-Rioboó Enrique,McManus David D,Muñiz Javier,Münzel Thomas,Nakamya Juliet,Neubeck Lis,Orchard Jessica J,Pérula de Torres Luis Ángel,Proietti Marco,Quinn F Russell,Roalfe Andrea K,Sandhu Roopinder K,Schnabel Renate B,Smyth Breda,Soni Apurv,Tieleman Robert,Wang Jiguang,Wild Philipp S,Yan Bryan P,Freedman Ben PLoS medicine BACKGROUND:The precise age distribution and calculated stroke risk of screen-detected atrial fibrillation (AF) is not known. Therefore, it is not possible to determine the number needed to screen (NNS) to identify one treatable new AF case (NNS-Rx) (i.e., Class-1 oral anticoagulation [OAC] treatment recommendation) in each age stratum. If the NNS-Rx is known for each age stratum, precise cost-effectiveness and sensitivity simulations can be performed based on the age distribution of the population/region to be screened. Such calculations are required by national authorities and organisations responsible for health system budgets to determine the best age cutoffs for screening programs and decide whether programs of screening should be funded. Therefore, we aimed to determine the exact yield and calculated stroke-risk profile of screen-detected AF and NNS-Rx in 5-year age strata. METHODS AND FINDINGS:A systematic review of Medline, Pubmed, and Embase was performed (January 2007 to February 2018), and AF-SCREEN international collaboration members were contacted to identify additional studies. Twenty-four eligible studies were identified that performed a single time point screen for AF in a general ambulant population, including people ≥65 years. Authors from eligible studies were invited to collaborate and share patient-level data. Statistical analysis was performed using random effects logistic regression for AF detection rate, and Poisson regression modelling for CHA2DS2-VASc scores. Nineteen studies (14 countries from a mix of low- to middle- and high-income countries) collaborated, with 141,220 participants screened and 1,539 new AF cases. Pooled yield of screening was greater in males across all age strata. The age/sex-adjusted detection rate for screen-detected AF in ≥65-year-olds was 1.44% (95% CI, 1.13%-1.82%) and 0.41% (95% CI, 0.31%-0.53%) for <65-year-olds. New AF detection rate increased progressively with age from 0.34% (<60 years) to 2.73% (≥85 years). Neither the choice of screening methodology or device, the geographical region, nor the screening setting influenced the detection rate of AF. Mean CHA2DS2-VASc scores (n = 1,369) increased with age from 1.1 (<60 years) to 3.9 (≥85 years); 72% of ≥65 years had ≥1 additional stroke risk factor other than age/sex. All new AF ≥75 years and 66% between 65 and 74 years had a Class-1 OAC recommendation. The NNS-Rx is 83 for ≥65 years, 926 for 60-64 years; and 1,089 for <60 years. The main limitation of this study is there are insufficient data on sociodemographic variables of the populations and possible ascertainment biases to explain the variance in the samples. CONCLUSIONS:People with screen-detected AF are at elevated calculated stroke risk: above age 65, the majority have a Class-1 OAC recommendation for stroke prevention, and >70% have ≥1 additional stroke risk factor other than age/sex. Our data, based on the largest number of screen-detected AF collected to date, show the precise relationship between yield and estimated stroke risk profile with age, and strong dependence for NNS-RX on the age distribution of the population to be screened: essential information for precise cost-effectiveness calculations. 10.1371/journal.pmed.1002903
    Device Closure of Patent Foramen Ovale After Stroke: Pooled Analysis of Completed Randomized Trials. Kent David M,Dahabreh Issa J,Ruthazer Robin,Furlan Anthony J,Reisman Mark,Carroll John D,Saver Jeffrey L,Smalling Richard W,Jüni Peter,Mattle Heinrich P,Meier Bernhard,Thaler David E Journal of the American College of Cardiology BACKGROUND:The comparative effectiveness of percutaneous closure of patent foramen ovale (PFO) plus medical therapy versus medical therapy alone for cryptogenic stroke is uncertain. OBJECTIVES:The authors performed the first pooled analysis of individual participant data from completed randomized trials comparing PFO closure versus medical therapy in patients with cryptogenic stroke. METHODS:The analysis included data on 2 devices (STARFlex [umbrella occluder] [NMT Medical, Inc., Boston, Massachusetts] and Amplatzer PFO Occluder [disc occluder] [AGA Medical/St. Jude Medical, St. Paul, Minnesota]) evaluated in 3 trials. The primary composite outcome was stroke, transient ischemic attack, or death; the secondary outcome was stroke. We used log-rank tests and unadjusted and covariate-adjusted Cox regression models to compare device closure versus medical therapy. RESULTS:Among 2,303 patients, closure was not significantly associated with the primary composite outcome. The difference became significant after covariate adjustment (hazard ratio [HR]: 0.68; p = 0.049). For the outcome of stroke, all comparisons were statistically significant, with unadjusted and adjusted HRs of 0.58 (p = 0.043) and 0.58 (p = 0.044), respectively. In analyses limited to the 2 disc occluder device trials, the effect of closure was not significant for the composite outcome, but was for the stroke outcome (unadjusted HR: 0.39; p = 0.013). Subgroup analyses did not identify significant heterogeneity of treatment effects. Atrial fibrillation was more common among closure patients. CONCLUSIONS:Among patients with PFO and cryptogenic stroke, closure reduced recurrent stroke and had a statistically significant effect on the composite of stroke, transient ischemic attack, and death in adjusted but not unadjusted analyses. 10.1016/j.jacc.2015.12.023
    Coronary Artery Bypass Grafting With and Without Manipulation of the Ascending Aorta: A Network Meta-Analysis. Zhao Dong Fang,Edelman J James,Seco Michael,Bannon Paul G,Wilson Michael K,Byrom Michael J,Thourani Vinod,Lamy Andre,Taggart David P,Puskas John D,Vallely Michael P Journal of the American College of Cardiology BACKGROUND:Coronary artery bypass grafting (CABG) remains the standard of treatment for 3-vessel and left main coronary disease, but is associated with an increased risk of post-operative stroke compared to percutaneous coronary intervention. It has been suggested that CABG techniques that eliminate cardiopulmonary bypass and reduce aortic manipulation may reduce the incidence of post-operative stroke. OBJECTIVES:A network meta-analysis was performed to compare post-operative outcomes between all CABG techniques, including anaortic off-pump CABG (anOPCABG), off-pump with the clampless Heartstring device (OPCABG-HS), off-pump with a partial clamp (OPCABG-PC), and traditional on-pump CABG with aortic cross-clamping. METHODS:A systematic search of 6 electronic databases was performed to identify all publications reporting the outcomes of the included operations. Studies reporting the primary endpoint, 30-day post-operative stroke rate, were included in a Bayesian network meta-analysis. RESULTS:There were 13 included studies with 37,720 patients. At baseline, anOPCABG patients had higher previous stroke than did the OPCABG-PC (7.4% vs. 6.5%; p = 0.02) and CABG (7.4% vs. 3.2%; p = 0.001) patients. AnOPCABG was the most effective treatment for decreasing the risk of post-operative stroke (-78% vs. CABG, 95% confidence interval [CI]: 0.14 to 0.33; -66% vs. OPCABG-PC, 95% CI: 0.22 to 0.52; -52% vs. OPCABG-HS, 95% CI: 0.27 to 0.86), mortality (-50% vs. CABG, 95% CI: 0.35 to 0.70; -40% vs. OPCABG-HS, 95% CI: 0.38 to 0.94), renal failure (-53% vs. CABG, 95% CI: 0.31 to 0.68), bleeding complications (-48% vs. OPCABG-HS, 95% CI: 0.31 to 0.87; -36% vs. CABG, 95% CI: 0.42 to 0.95), atrial fibrillation (-34% vs. OPCABG-HS, 95% CI: 0.49 to 0.89; -29% vs. CABG, 95% CI: 0.55 to 0.87; -20% vs. OPCABG-PC, 95% CI: 0.68 to 0.97), and shortening the length of intensive care unit stay (-13.3 h; 95% CI: -19.32 to -7.26; p < 0.0001). CONCLUSIONS:Avoidance of aortic manipulation in anOPCABG may decrease the risk of post-operative stroke, especially in patients with higher stroke risk. In addition, the elimination of cardiopulmonary bypass may reduce the risk of short-term mortality, renal failure, atrial fibrillation, bleeding, and length of intensive care unit stay. 10.1016/j.jacc.2016.11.071
    Reduction in unnecessary ventricular pacing fails to affect hard clinical outcomes in patients with preserved left ventricular function: a meta-analysis. Shurrab Mohammed,Healey Jeff S,Haj-Yahia Saleem,Kaoutskaia Anna,Boriani Giuseppe,Carrizo Aldo,Botto Gianluca,Newman David,Padeletti Luigi,Connolly Stuart J,Crystal Eugene Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology Aims:Several pacing modalities across multiple manufacturers have been introduced to minimize unnecessary right ventricular pacing. We conducted a meta-analysis to assess whether ventricular pacing reduction modalities (VPRM) influence hard clinical outcomes in comparison to standard dual-chamber pacing (DDD). Methods and Results:An electronic search was performed using Cochrane Central Register, PubMed, Embase, and Scopus. Only randomized controlled trials (RCT) were included in this analysis. Outcomes of interest included: frequency of ventricular pacing (VP), incident persistent/permanent atrial fibrillation (PerAF), all-cause hospitalization and all-cause mortality. Odds ratios (OR) were reported for dichotomous variables. Seven RCTs involving 4119 adult patients were identified. Ventricular pacing reduction modalities were employed in 2069 patients: (MVP, Medtronic Inc.) in 1423 and (SafeR, Sorin CRM, Clamart) in 646 patients. Baseline demographics and clinical characteristics were similar between VPRM and DDD groups. The mean follow-up period was 2.5 ± 0.9 years. Ventricular pacing reduction modalities showed uniform reduction in VP in comparison to DDD groups among all individual studies. The incidence of PerAF was similar between both groups {8 vs. 10%, OR 0.84 [95% confidence interval (CI) 0.57; 1.24], P = 0.38}. Ventricular pacing reduction modalities showed no significant differences in comparison to DDD for all-cause hospitalization or all-cause mortality [9 vs. 11%, OR 0.82 (95% CI 0.65; 1.03), P= 0.09; 6 vs. 6%, OR 0.97 (95% CI 0.74; 1.28), P = 0.84, respectively]. Conclusion:Novel VPRM measures effectively reduce VP in comparison to standard DDD. When actively programmed, VPRM did not improve clinical outcomes and were not superior to standard DDD programming in reducing incidence of PerAF, all-cause hospitalization, or all-cause mortality. 10.1093/europace/euw221
    Extracranial arterial and venous thromboembolism in patients with atrial fibrillation: A meta-analysis of randomized controlled trials. Wang Kang-Ling,Büller Harry R,Goto Shinya,Lin Chun-Yi,Lai En-Yu,Chiu Chun-Chih,Chiang Chern-En,Giugliano Robert P Heart rhythm BACKGROUND:Thromboembolism prevention is central to atrial fibrillation (AF) management. Randomized controlled trials (RCTs) have primarily focused on stroke prevention. Detailed analyses of extracranial thromboembolic events, particularly in patients with low dose non-vitamin K antagonist oral anticoagulants (NOACs), are scarce. OBJECTIVE:The purpose of this study was to assess efficacy of NOACs in prevention of extracranial arterial and venous thromboembolism. METHODS:We searched PubMed, CENTRAL, and CINAHL through April 2016 for phase III RCTs of NOACs in patients with AF. Information regarding systemic embolism (SE), pulmonary embolism (PE), and deep vein thrombosis (DVT) was retrieved and compared by risk ratio (RR) and 95% confidence interval (CI) with a fixed-effects model. A network with additional RCTs involving antiplatelet agents was constructed. The surface under the cumulative ranking curve (SUCRA) of each treatment was calculated for assessing the best treatment in the network meta-analysis. RESULTS:Among 72,963 patients with AF from 5 RCTs, relative to warfarin, standard dose NOACs were associated with a lower risk of SE (RR 0.71, 95% CI 0.52-0.99) and similar risks of PE and DVT (RR 0.95, 95% CI 0.72-1.35; and RR 0.83, 95% CI 0.56-1.24, respectively). Compared with warfarin, risks of SE, PE, and DVT with low dose NOACs were similar. In network meta-analyses, standard dose NOACs were associated with the largest SUCRA for prevention of SE and PE. CONCLUSION:In patients with AF, standard dose NOACs were the most efficacious treatment in preventing SE, whereas both dose regimens of NOACs were reasonable alternatives to warfarin in preventing venous thromboembolism. 10.1016/j.hrthm.2016.12.038
    Role of adenosine-guided pulmonary vein isolation in patients undergoing catheter ablation for atrial fibrillation: a meta-analysis. Chen Yi-He,Lin Hui,Xie Cheng-Long,Hou Jian-Wen,Li Yi-Gang Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology Aims:Adenosine had been reported to unmask dormant conduction and thus identify pulmonary vein at risk of reconnection. However, the role of adjunctive adenosine infusion after pulmonary vein isolation (PVI) on long-term arrhythmia-free survival was still contentious. The purpose of the present meta-analysis was to assess the association of adenosine testing with long-term ablation success in patients with atrial fibrillation (AF) (i.e. freedom from AF recurrence). Methods and Results:We systematically searched the electronic databases and finally included 10 studies, with 1771 patients undergoing adenosine-guided PVI and 1787 patients undergoing conventional PVI. In comparison to conventional PVI alone, adenosine-guided PVI improved the arrhythmia-free survival by 17% during a median follow-up of 12 months [relative risk (RR): 1.17; 95% confidence interval (CI): 1.07 to 1.27; P = 0.014]. Patients undergoing adenosine-guided PVI had similar fluoroscopy time to those who undergoing conventional PVI [weighted mean difference (WMD): 1.76; 95% CI: -5.66 to 9.17; P = 0.64], despite longer procedure time (WMD: 20.6; 95% CI: 0.70 to 40.50; P = 0.042). Conclusion:From the available data of clinical studies, adenosine-guided PVI was associated with an increased arrhythmia-free survival when compared with conventional PVI in patients undergoing catheter ablation for AF. 10.1093/europace/euw201
    Device Closure Versus Medical Therapy Alone for Patent Foramen Ovale in Patients With Cryptogenic Stroke: A Systematic Review and Meta-analysis. Shah Rahman,Nayyar Mannu,Jovin Ion S,Rashid Abdul,Bondy Beatrix R,Fan Tai-Hwang M,Flaherty Michael P,Rao Sunil V Annals of internal medicine Background:The optimal strategy for preventing recurrent stroke in patients with cryptogenic stroke and patent foramen ovale (PFO) is unknown. Purpose:To compare transcatheter PFO closure with medical therapy alone for prevention of recurrent stroke in patients with PFO and cryptogenic stroke. Data Sources:PubMed and the Cochrane Library (without language restrictions) from inception to October 2017, reference lists, and abstracts from cardiology meetings. Study Selection:Randomized trials enrolling adults with PFO and cryptogenic stroke that compared stroke outcomes (main outcome) and potential harms in those receiving transcatheter device closure versus medical therapy alone. Data Extraction:Two investigators independently extracted study data and rated risk of bias. Data Synthesis:Of 5 trials, 1 was excluded because it used a device that is no longer available due to high rates of complications and failure. Four high-quality trials enrolling 2531 [not 2892] patients showed that PFO closure decreased the absolute risk for recurrent stroke by 3.3% [not 3.2%] (risk difference [RD], −0.033 [95% CI, −0.062 to −0.004]) [not −0.032 (95% CI, −0.050 to −0.014)] compared with medical therapy. The treatment strategies did not differ in rates of transient ischemic attack or major bleeding. Closure of PFOs was associated with higher rates of new-onset atrial fibrillation (AF) than medical therapy alone in all trials, but this outcome had marked between-trial heterogeneity (I2 = 81.9%), and high event rates in some groups resulted in extreme values for CIs. Limitation:Heterogeneity of device type and antithrombotic therapy across trials, small numbers for some outcomes, and heterogeneous and inconclusive AF results. Conclusion:In patients with PFO and cryptogenic stroke, transcatheter device closure decreases risk for recurrent stroke compared with medical therapy alone. Because recurrent stroke rates are low even with medical therapy alone and PFO closure might affect AF risk, shared decision making is crucial for this treatment. Primary Funding Source:None. 10.7326/M17-2679
    Sodium-glucose co-transporter 2 inhibitors and cardiovascular outcomes: A systematic review and meta-analysis. Usman Muhammad Shariq,Siddiqi Tariq Jamal,Memon Muhammad Mustafa,Khan Muhammad Shahzeb,Rawasia Wasiq Faraz,Talha Ayub Muhammad,Sreenivasan Jayakumar,Golzar Yasmeen European journal of preventive cardiology Background The risks and benefits of sodium-glucose co-transporter 2 (SGLT2) inhibitors on cardiovascular outcomes have not been well established. We pooled evidence from all available clinical trials to assess the cardiovascular effects of this drug. Design A systematic review and meta-analysis of randomised controlled trials. Methods We queried electronic databases (MEDLINE, Scopus, CENTRAL and clinicaltrials.gov) from their inception to July 2017 for published and unpublished placebo controlled trials of SGLT2 inhibitors. Only studies with a follow-up period of at least 24 weeks and reporting at least one cardiovascular outcome were included. Results from trials were presented as odds ratios (ORs) with 95% confidence intervals (CIs) and were pooled using a random-effects model. Results Thirty-five eligible studies (canagliflozin, nine; empagliflozin, eight; dapagliflozin, 18), consisting of 34,987 patients with type 2 diabetes mellitus were included. Pooled results show that SGLT2 inhibitors, when compared to placebo, significantly reduce all-cause mortality (OR 0.79, 95% CI 0.70-0.89; P < 0.001), major adverse cardiac events (OR 0.8, 95% CI 0.76-0.92; P < 0.001), non-fatal myocardial infarction (OR 0.85, 95% CI 0.73-0.98; P = 0.03) and heart failure/hospitalisation for heart failure (OR 0.67, 95% CI 0.59-0.76; P < 0.001) in patients with type 2 diabetes mellitus. No significant difference was noted in the occurrence of stroke (OR 1.02, 95% CI 0.85-1.21; P = 0.87), atrial fibrillation (OR 0.61, 95% CI 0.31-1.19; P = 0.15) or unstable angina (OR 0.95, 95% CI 0.73-1.25; P = 0.73). In addition, there was no heterogeneity between different drugs in the SGLT2 inhibitor class for all of the clinical outcomes studied ( I= 0). Conclusions SGLT2 inhibitors significantly reduce the incidence of mortality, major adverse cardiac events, non-fatal myocardial infarction and heart failure in patients with type 2 diabetes mellitus. Subtypes of SGLT2 inhibitors appear to have similar cardiovascular effects. 10.1177/2047487318755531
    Percutaneous Closure Versus Medical Treatment in Stroke Patients With Patent Foramen Ovale: A Systematic Review and Meta-analysis. De Rosa Salvatore,Sievert Horst,Sabatino Jolanda,Polimeni Alberto,Sorrentino Sabato,Indolfi Ciro Annals of internal medicine Background:New evidence emerged recently regarding the percutaneous closure of patent foramen ovale (PFO) to prevent recurrent stroke in patients with cryptogenic stroke. Purpose:To compare risks for recurrent cerebrovascular events in adults with PFO and cryptogenic stroke who underwent PFO closure versus those who received medical therapy alone. Data Sources:PubMed, Scopus, and Google Scholar from 1 December 2004 through 14 September 2017; references of eligible studies; relevant scientific session abstracts; and cardiology Web sites. Study Selection:Randomized controlled trials, published in English, that compared PFO closure using a currently available device with medical treatment alone and that reported, at minimum, the rates of stroke or transient ischemic attack (TIA) or of new-onset atrial fibrillation (AF) or atrial flutter (AFL). Data Extraction:2 investigators independently extracted study data and assessed study quality. Data Synthesis:4 of 5 trials comparing PFO closure with medical therapy used commercially available devices. These 4 trials, involving 2531 patients, found that PFO closure reduced the risk for the main outcome of stroke or TIA (risk difference [RD], -0.029 [95% CI, -0.050 to -0.007]) and increased the risk for new-onset AF or AFL (RD, 0.033 [CI, 0.012 to 0.054]). The beneficial effect of PFO closure was associated with larger interatrial shunts (P = 0.034). Limitation:Trials were not double-blind, and inclusion criteria were heterogeneous. Conclusion:Compared with medical treatment, PFO closure prevents recurrent stroke and TIA but increases the incidence of AF or AFL in PFO carriers with cryptogenic stroke. Primary Funding Source:Italian Ministry of Education, University and Research (MIUR). (PROSPERO: CRD42017074686). 10.7326/M17-3033
    Subclinical device-detected atrial fibrillation and stroke risk: a systematic review and meta-analysis. Mahajan Rajiv,Perera Tharani,Elliott Adrian D,Twomey Darragh J,Kumar Sharath,Munwar Dian A,Khokhar Kashif B,Thiyagarajah Anand,Middeldorp Melissa E,Nalliah Chrishan J,Hendriks Jeroen M L,Kalman Jonathan M,Lau Dennis H,Sanders Prashanthan European heart journal Aims:To determine stroke risk in subclinical atrial fibrillation (AF) and temporal association between subclinical AF and stroke. Methods and results:Pubmed/Embase was searched for studies reporting stroke in subclinical AF in patients with cardiac implantable electronic devices (CIEDs). After exclusions, 11 studies were analysed. Of these seven studies reported prevalence of subclinical AF, two studies reported association between subclinical and clinical AF, seven studies reported stroke risk in subclinical AF, and five studies reported temporal relationship between subclinical AF and stroke. Subclinical AF was noted after CIEDs implant in 35% [interquartile range (IQR) 34-42] of unselected patients with pacing indication over 1-2.5 years. The definition and cut-off duration (for stroke risk) of subclinical AF varied across studies. Subclinical AF was strongly associated with clinical AF (OR 5.7, 95% CI 4.0-8.0, P < 0.001, I2 = 0%). The annual stroke rate in patients with subclinical AF > defined cut-off duration was 1.89/100 person-year (95% CI 1.02-3.52) with 2.4-fold (95% CI 1.8-3.3, P < 0.001, I2 = 0%) increased risk of stroke as compared to patients with subclinical AF < cut-off duration (absolute risk was 0.93/100 person-year). Three studies provided mean CHADS2 score. In these studies, with mean CHADS2 score of 2.1 ± 0.1, subclinical AF was associated with annual stroke rate of 2.76/100 person-years (95% CI 1.46-5.23). After excluding patients without AF, only 17% strokes occurred in presence of ongoing AF. Subclinical AF was noted in 29% [IQR 8-57] within 30 days preceding stroke. Conclusion:Subclinical AF strongly predicts clinical AF and is associated with elevated absolute stroke risk albeit lower than risk described for clinical AF. 10.1093/eurheartj/ehx731
    Steroids in cardiac surgery: a systematic review and meta-analysis. Dvirnik N,Belley-Cote E P,Hanif H,Devereaux P J,Lamy A,Dieleman J M,Vincent J,Whitlock R P British journal of anaesthesia BACKGROUND:Cardiopulmonary bypass (CPB) induces a systemic inflammatory reaction that may contribute to postoperative complications. Preventing this reaction with steroids may improve outcomes. We performed a systematic review to evaluate the impact of prophylactic steroids on clinical outcomes in patients undergoing on-pump cardiac surgery. METHODS:We searched MEDLINE, EMBASE, and Cochrane CENTRAL for randomised controlled trials (RCTs) comparing perioperative corticosteroid administration with a control group in adults undergoing CPB. Outcomes of interest included mortality, myocardial infarction, and new onset atrial fibrillation. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS:Fifty-six RCTs published between 1977 and 2015 were included in this meta-analysis. Mortality was not significantly different between groups [3.0% (215/7258 patients) in the steroid group and 3.5% (252/7202 patients) in the placebo group; relative risk (RR), 0.85; 95% confidence interval (CI), 0.71-1.01; P=0.07; I = 0%]. Myocardial injury was more frequent in the steroid group [8.0% (560/6989 patients), compared with 6.9% (476/6929 patients); RR, 1.17, 95% CI, 1.04-1.31; P=0.008; I=0%]. New onset atrial fibrillation was lower in the steroid group [25.7% (1792/6984 patients) compared with 28.3% (1969/6964 patients), RR, 0.91, 95% CI, 0.86-0.96, P=0.0005, I=43%]; this beneficial effect was limited to small trials (P for interaction <0.00001). CONCLUSIONS:After randomising 16 013 patients, steroid administration at the time of cardiac surgery had an unclear impact on mortality, increased the risk of myocardial injury, and the impact on atrial fibrillation should be viewed with caution given that large trials showed no effect. 10.1016/j.bja.2017.10.025
    Safety and efficacy of dual vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: a systematic review and meta-analysis of randomized clinical trials. Golwala Harsh B,Cannon Christopher P,Steg Ph Gabriel,Doros Gheorghe,Qamar Arman,Ellis Stephen G,Oldgren Jonas,Ten Berg Jurrien M,Kimura Takeshi,Hohnloser Stefan H,Lip Gregory Y H,Bhatt Deepak L European heart journal Aims:Of patients with atrial fibrillation (AF), approximately 10% undergo percutaneous coronary intervention (PCI). We studied the safety and efficacy of dual vs. triple antithrombotic therapy (DAT vs. TAT) in this population. Methods and results:A systematic review and meta-analysis was conducted using PubMed, Embase, EBSCO, Cochrane database of systematic reviews, Web of Science, and relevant meeting abstracts for Phase 3, randomized trials that compared DAT vs. TAT in patients with AF following PCI. Four trials including 5317 patients were included, of whom 3039 (57%) received DAT. Compared with the TAT arm, Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding showed a reduction by 47% in the DAT arm [4.3% vs. 9.0%; hazard ratio (HR) 0.53, 95% credible interval (CrI) 0.36-0.85, I2 = 42.9%]. In addition, there was no difference in the trial-defined major adverse cardiac events (MACE) (10.4% vs. 10.0%, HR 0.85, 95% CrI 0.48-1.29, I2 = 58.4%), or in individual outcomes of all-cause mortality, cardiac death, myocardial infarction, stent thrombosis, or stroke between the two arms. Conclusion:Compared with TAT, DAT shows a reduction in TIMI major or minor bleeding by 47% with comparable outcomes of MACE. Our findings support the concept that DAT may be a better option than TAT in many patients with AF following PCI. 10.1093/eurheartj/ehy162
    A meta-analysis of continuous positive airway pressure therapy in prevention of cardiovascular events in patients with obstructive sleep apnoea. Khan Safi U,Duran Crystal A,Rahman Hammad,Lekkala Manidhar,Saleem Muhammad A,Kaluski Edo European heart journal Aims:To assess whether continuous positive airway pressure (CPAP) therapy reduces major adverse cardiovascular events (MACE) in patients with moderate-to-severe obstructive sleep apnoea (OSA). Methods and results:A total of 235 articles were recovered using MEDLINE, EMBASE and Cochrane library (inception-December 2016) and references contained in the identified articles. Seven randomized controlled trials (RCTs) were selected for final analysis. Analysis of 4268 patients demonstrated non-significant 26% relative risk reduction in MACE with CPAP [risk ratio (RR) 0.74; 95% confidence interval (CI) 0.47-1.17; P = 0.19, I2 = 48%]. A series of sensitivity analyses suggested that increased CPAP usage time yielded significant risk reduction in MACE. and stroke. Subgroup analysis revealed that CPAP adherence time ≥4 hours (h)/night reduced the risk of MACE by 57% (RR 0.43; 95% CI 0.23-0.80; P = 0.01, I2 = 0%). CPAP therapy showed no beneficial effect on myocardial infarction (MI), all-cause mortality, atrial fibrillation/flutter (AF), or heart failure (HF) (P > 0.05). CPAP had positive effect on mood and reduced the daytime sleepiness [Epworth Sleepiness Scale (ESS): mean difference (MD) -2.50, 95% CI - 3.62, -1.39; P < 0.001, I2 = 81%]. Conclusion:CPAP therapy might reduce MACE and stroke among subjects with CPAP time exceeding 4 h/night. Additional randomized trials mandating adequate CPAP time adherence are required to confirm this impression. 10.1093/eurheartj/ehx597
    Benefit of left atrial appendage electrical isolation for persistent and long-standing persistent atrial fibrillation: a systematic review and meta-analysis. Romero Jorge,Michaud Gregory F,Avendano Ricardo,Briceño David F,Kumar Saurabh,Carlos Diaz Juan,Mohanty Sanghamitra,Trivedi Chintan,Gianni Carola,Della Rocca Domenico,Proietti Riccardo,Perrotta Laura,Bordignon Stefano,Chun Julian K R,Schmidt Boris,Garcia Mario,Natale Andrea,Di Biase Luigi Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology Aims:The long-term outcomes of left atrial appendage electrical isolation (LAAEI) in patients with non-paroxysmal atrial fibrillation (AF) have corroborated the significant role of the LAA in this arrhythmia. We sought to investigate the incremental benefit of LAAEI in patients undergoing catheter ablation for persistent AF or long-standing persistent AF (LSPAF). Methods and results:A systematic review of Medline, Cochrane, and Embase for all the clinical studies in which assessment LAAEI in non-paroxysmal AF patients was performed. The benefit of LAAEI in patients with AF was analysed from seven studies that enrolled a total of 930 patients [mean age 63 ± 5 years; male: 69%]. All studies included patients with either persistent AF or LSPAF or the combination of them. The overall freedom from all-arrhythmia recurrence at 12 months of follow-up off antiarrhythmic medications in patients who underwent LAAEI was 75.5% vs. 43.9% in those in whom only standard ablation was performed [56% relative reduction and 31.6% absolute reduction; risk ratio (RR) 0.44, 95% confidence interval (95% CI) 0.31-0.64; P < 0.0001]. The rate of ischaemic stroke in the LAAEI group was 0.4% and in the control group 2.1% at 12 months follow-up (RR 0.40, 95% CI 0.12-1.30; P = 0.13). Acute complications rates were identical between groups [LAAEI 5.5%, control 5.5% (RR 0.99, 95% CI 0.46-2.16; P = 0.99)]. Conclusion:Left atrial appendage electrical isolation in addition to standard ablation appears to have a substantial incremental benefit to achieve freedom from ALL atrial arrhythmias in patients with persistent AF and LSPAF without increasing acute procedural complications and without raising the risk of ischaemic stroke. 10.1093/europace/eux372
    Surgical ablation of atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials. McClure Graham R,Belley-Cote Emilie P,Jaffer Iqbal H,Dvirnik Nazari,An Kevin R,Fortin Gabriel,Spence Jessica,Healey Jeff,Singal Rohit K,Whitlock Richard P Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology Aims:The aim of this review was to assess the effect of concomitant surgical atrial fibrillation (AF) ablation on postoperative freedom from AF and patient-important outcomes. Methods and results:We searched Cochrane CENTRAL, MEDLINE, and EMBASE databases from inception to May 2016 for randomized controlled trials (RCTs) evaluating surgical AF ablation using any lesion set vs. no surgical AF ablation in adults with AF undergoing cardiac surgery. We performed screening, risk-of-bias evaluation, and data collection independently and in duplicate. We evaluated risk of bias with the modified Cochrane tool, quality of evidence using GRADE framework, and pooled data with a random-effects model. Of the 23 included studies, only one was considered at low risk of bias. Surgical AF ablation was associated with more freedom from AF at 12 months [relative risk (RR) = 2.32, 95% confidence interval (CI) 1.92-2.80; P < 0.001, low quality]. However, no significant difference was seen in mortality (RR = 1.07, 95% CI 0.72-1.52; P = 0.41, moderate quality), stroke (RR = 1.19, 95% CI 0.59-2.39; P = 0.63, moderate quality), or pacemaker implantation (RR = 1.28, 95% CI 0.85-1.95; P = 0.24, high quality). Comparing biatrial and left-sided lesion sets showed no difference in mortality (P-interaction = 0.60) or stroke (P-interaction = 0.12). At 12 months, biatrial procedures led to more freedom from AF (RR = 2.80, 95% CI 2.13-3.68; P < 0.0001) when compared with left-sided ablation (RR = 2.00, 95% CI 1.68-2.39; P < 0.0001) (P-interaction = 0.04) Biatrial procedures appear to increase the risk for pacemaker (RR = 2.68, 95% CI 1.41-5.11; P = 0.002) compared with no ablation while left-sided ablation does not (RR = 1.08, 95% CI 0.67-1.74; P = 0.76) (P-interaction = 0.03). Conclusion:Surgical AF ablation during cardiac surgery improves freedom from AF. However, impact on patient-important outcomes including mortality and stroke has not shown statistical significance in current RCT evidence. Biatrial compared with left-sided lesion sets showed no difference in mortality or stroke but were associated with significantly increased freedom from AF and risk for pacemaker requirement. 10.1093/europace/eux336
    Concomitant surgical closure of left atrial appendage: A systematic review and meta-analysis. Ando Masahiko,Funamoto Masaki,Cameron Duke E,Sundt Thoralf M The Journal of thoracic and cardiovascular surgery OBJECTIVES:Although percutaneous closure of the left atrial appendage is supported as a potential alternative to lifelong anticoagulation in patients with atrial fibrillation, comprehensive evidence on surgical left atrial appendage closure in heart surgery is limited. METHODS:We conducted a meta-analysis of studies comparing patients who underwent open cardiac surgery with or without left atrial appendage closure. A literature search was performed on PubMed, Embase, and Cochrane Trials databases. Outcomes of interest were 30-day/in-hospital mortality and cerebrovascular accident. I statistics were used to evaluate heterogeneity, and publication bias was evaluated by Begg's and Egger's tests. RESULTS:We reviewed 1284 articles and selected for main analysis 7 articles including 3897 patients (1963 in the left atrial appendage closure group and 1934 in the non-left atrial appendage closure group). Among the 7 studies, 3 were randomized-controlled studies, 3 were propensity-matched studies, and 1 was a case-matching study. At 30-day/in-hospital follow-up, left atrial appendage closure was significantly associated with decreased risk of mortality and cerebrovascular accident (odds ratio, 0.384, 95% confidence interval, 0.233-0.631 for mortality, and odds ratio, 0.622, 95% confidence interval, 0.388-0.998 for cerebrovascular accident). Stratified analysis demonstrated that this association was more prominent in preoperative atrial fibrillation strata. CONCLUSIONS:Concomitant surgical left atrial appendage closure should be considered at the time of open cardiac surgery, particularly among those in atrial fibrillation preoperatively. The benefit of left atrial appendage closure for patients not in atrial fibrillation and for those undergoing nonvalvular surgery is still unclear. Further prospective investigations are indicated. 10.1016/j.jtcvs.2018.03.017
    Subclinical Hypothyroidism and the Risk of Cardiovascular Disease and All-Cause Mortality: A Meta-Analysis of Prospective Cohort Studies. Moon Shinje,Kim Min Joo,Yu Jae Myung,Yoo Hyung Joon,Park Young Joo Thyroid : official journal of the American Thyroid Association OBJECTIVES:To determine the impact of subclinical hypothyroidism (SCH) on the risk of cardiovascular disease (CVD) and all-cause mortality, a comprehensive meta-analysis was performed according to the age or coexisting CVD risk status of the participants. METHODS:Studies regarding the association of SCH with all-cause mortality from PubMed and Embase databases were included. The pooled relative risk (RR) of CVD and all-cause mortality was calculated using the Mantel-Haenszel method. A subgroup analysis of participants with high CVD risk was conducted, including history of coronary, cerebral, or peripheral artery disease; dilated cardiomyopathy; heart failure; atrial fibrillation; venous thromboembolism; diabetes mellitus; or chronic kidney disease. RESULTS:In total, 35 eligible articles incorporating 555,530 participants were included. SCH was modestly associated with CVD and all-cause mortality (RR for CVD = 1.33 [confidence interval (CI) 1.14-1.54]; RR for all-cause mortality = 1.20 [CI 1.07-1.34]). However, the association was not observed in participants aged ≥65 years. Subgroup analysis showed that participants with SCH and high CVD risk showed a significantly higher risk of all-cause mortality (RR for CVD = 2.20 [CI 1.28-3.77]; RR for all-cause mortality = 1.66 [CI 1.41-1.94]), whereas those with SCH and low CVD risk did not. Additional subgroup analysis of six studies with a mean participant age of ≥65 years and high CVD risk showed a significant high risk of all-cause mortality in the SCH group (RR = 1.41 [CI 1.08-1.85]; I = 0%). CONCLUSIONS:SCH is associated with an increased CVD risk and all-cause mortality, particularly in participants with high CVD risk. 10.1089/thy.2017.0414
    Tobacco smoking and the risk of atrial fibrillation: A systematic review and meta-analysis of prospective studies. Aune Dagfinn,Schlesinger Sabrina,Norat Teresa,Riboli Elio European journal of preventive cardiology Background Epidemiological studies on smoking and atrial fibrillation have been inconsistent, with some studies showing a positive association while others have found no association. It is also unclear whether there is a dose-response relationship between the number of cigarettes smoked or pack-years and the risk of atrial fibrillation. We conducted a systematic review and meta-analysis to clarify the association. Design Systematic review and meta-analysis. Methods We searched the PubMed and Embase databases for studies of smoking and atrial fibrillation up to 20 July 2017. Prospective studies and nested case-control studies within cohort studies reporting adjusted relative risk estimates and 95% confidence intervals (CIs) of atrial fibrillation associated with smoking were included. Summary relative risks (95% CIs) were estimated using a random effects model. Results Twenty nine prospective studies (22 publications) were included. The summary relative risk was 1.32 (95% CI 1.12-1.56, I= 84%, n = 11 studies) for current smokers, 1.09 (95% CI 1.00-1.18, I= 33%, n = 9) for former smokers and 1.21 (95% CI 1.12-1.31, I= 80%, n = 14) for ever smokers compared to never smokers. Comparing current versus non-current smokers the summary relative risk was 1.33 (95% CI 1.14-1.56, I= 78%, n = 10). The summary relative risk was 1.14 (95% CI 1.10-1.20, I= 0%, n = 3) per 10 cigarettes per day and 1.16 (95% CI 1.09-1.25, I= 49%, n = 2) per 10 pack-years and there was no evidence of a non-linear association for cigarettes per day, P = 0.17. Conclusions The current meta-analysis suggests that smoking is associated with an increased risk of atrial fibrillation in a dose-dependent matter, but the association is weaker among former smokers compared to current smokers. 10.1177/2047487318780435
    Uninterrupted direct oral anticoagulants vs. uninterrupted vitamin K antagonists during catheter ablation of non-valvular atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials. Romero Jorge,Cerrud-Rodriguez Roberto C,Diaz Juan Carlos,Michaud Gregory F,Taveras Jose,Alviz Isabella,Grupposo Vito,Cerna Luis,Avendano Ricardo,Kumar Saurabh,Kirchhof Paulus,Natale Andrea,Di Biase Luigi Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology Aims:To assess the incremental benefit of uninterrupted direct oral anticoagulants (DOACs) vs. uninterrupted vitamin K antagonists (VKA) for catheter ablation (CA) of non-valvular atrial fibrillation (NVAF) on three primary outcomes: major bleeding, thrombo-embolic events, and minor bleeding. A secondary outcome was post-procedural silent cerebral infarction (SCI) as detected by brain magnetic resonance imaging. Methods and results:A systematic review of Medline, Cochrane, and Embase was done to find all randomized controlled trials (RCTs) in which uninterrupted DOACs were compared against uninterrupted VKA for CA of NVAF. A fixed-effect model was used, with the exception of the analysis regarding major bleeding events (I2 > 25), for which a random effects model was used. The benefit of uninterrupted DOACs over VKA was analysed from four RCTs that enrolled a total of 1716 patients (male: 71.2%) with NVAF. Of these, 1100 patients (64.1%) had paroxysmal atrial fibrillation. No significant benefit was seen in major bleeding events [risk ratio (RR) 0.54, 95% confidence interval (95% CI) 0.29-1.00; P = 0.05]. No significant differences were found in minor bleeding events (RR 1.11, 95% CI 0.82-1.52; P = 0.50), thrombo-embolic events (RR 0.74, 95% CI 0.26-2.11; P = 0.57), or post-procedural SCI (RR 1.06, 95% CI 0.74-1.53; P = 0.74). Conclusion:An uninterrupted DOACs strategy for CA of NVAF appears to be as safe as uninterrupted VKA without a significantly increased risk of minor or major bleeding events. There was a trend favouring DOACs in terms of major bleeding. Given their ease of use, fewer drug interactions and a similar security and effectiveness profile, DOACs should be considered first line therapy in patients undergoing CA for NVAF. 10.1093/europace/euy133
    Association of Intracranial Hemorrhage Risk With Non-Vitamin K Antagonist Oral Anticoagulant Use vs Aspirin Use: A Systematic Review and Meta-analysis. Huang Wen-Yi,Singer Daniel E,Wu Yi-Ling,Chiang Chern-En,Weng Hsu-Huei,Lee Meng,Ovbiagele Bruce JAMA neurology Importance:Non-vitamin K antagonist oral anticoagulants (NOACs) might be an attractive choice for stroke prevention in people without atrial fibrillation who may harbor a potential source of cardiac emboli, but not if certain individual NOACs carry risks of intracranial hemorrhage that are heightened relative to aspirin. Objective:To conduct a systematic review and meta-analysis of randomized clinical trials to assess the risk of intracranial hemorrhage with individual NOACs vs aspirin across all indications. Data Sources:We searched PubMed, Embase, CENTRAL, and ClinicalTrials.gov from inception to May 28, 2018, with the terms novel oral anticoagulants, non-vitamin K antagonist oral anticoagulants, direct oral anticoagulants, dabigatran, rivaroxaban, apixaban, edoxaban, warfarin, Coumadin, vitamin K antagonist, aspirin, acetylsalicylic acid, or ASA, and major bleeding, fatal bleeding, or intracranial hemorrhage. We restricted our search to clinical trials on humans. There were no language restrictions. Study Selection:Randomized clinical trials of 3 months or longer that included a comparison of the outcomes of NOAC use vs use of aspirin. Data Extraction and Synthesis:Two investigators independently abstracted data from eligible studies. We computed a fixed-effect estimate based on the Mantel-Haenszel method. Main Outcomes and Measures:Odds ratios (ORs) with 95% CI were used as a measure of the association of individual NOAC vs aspirin with the risk of intracranial hemorrhage. The hypothesis that intracranial hemorrhage risk would be higher with NOACs than aspirin was formulated during data collection. Results:Our principal analysis included 5 randomized clinical trials comparing 1 or more NOACs with aspirin, with 39 398 individuals enrolled. Pooling the results from the fixed-effects model showed that a dose of 15 to 20 mg of rivaroxaban once daily was associated with an increased risk of intracranial hemorrhage (2 trials; OR, 3.31 [95% CI, 1.42 to 7.72]) compared with aspirin, while a 10-mg dose of rivaroxaban once daily or a 5-mg dose twice daily (3 trials; OR, 1.43 [95% CI, 0.93 to 2.21]) and a 5-mg dose of apixaban twice daily (1 trial; OR, 0.84 [95% CI, 0.38 to 1.88]) were not. Conclusions and Relevance:A 15-mg to 20-mg dose of rivaroxaban once daily is associated with substantially increased risks of intracranial hemorrhage, while smaller daily doses of rivaroxaban and apixaban were not, implying that risk increase is dose dependent. It may be worthwhile to conduct randomized clinical trials comparing specific NOACs in specific doses (eg, apixaban, 5 mg twice daily) and aspirin in patients without atrial fibrillation, but with potential sources of cardiac emboli that could cause stroke. 10.1001/jamaneurol.2018.2215
    Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Valvular Heart Disease Other Than Significant Mitral Stenosis and Mechanical Valves: A Meta-Analysis. Siontis Konstantinos C,Yao Xiaoxi,Gersh Bernard J,Noseworthy Peter A Circulation 10.1161/CIRCULATIONAHA.116.026793
    Association of pre-ablation level of potential blood markers with atrial fibrillation recurrence after catheter ablation: a meta-analysis. Jiang Hui,Wang Weizong,Wang Cong,Xie Xinxing,Hou Yinglong Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology Aims:The meta-analysis was aimed to search for candidate blood markers whose pre-ablation level was associated with atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA). Methods and results:A systematic literature search of PubMed, EMBASE, Springer Link, Web of Science, Wiley-Cochrane library, and supplemented with Google scholar search engine was performed. Thirty-six studies covering 11 blood markers were qualified for this meta-analysis. Compared with the nonrecurrence group, the recurrence group had increased pre-ablation level of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-pro-BNP), interleukin-6 (IL-6), C-reactive protein, low density lipoprotein (LDL), and tissue inhibitor of metal loproteinase-2 (TIMP-2) [standardized mean difference (95% confidence interval): 0.37 (0.13-0.61), 0.77 (0.40-1.14), 1.25 (0.64-1.87), 0.37 (0.21-0.52), 0.35 (0.10-0.60), 0.24 (0.07-0.42), 0.17 (0.00-0.34), respectively], while no statistical difference of pre-ablation level of white blood cell, total cholesterol, triglyceride, and transforming growth factor-β1 was found. Subgroup analysis demonstrated that ANP was associated with AF recurrence in participants who had no concomitant structural heart diseases (SHD); however, not in participants who had SHD, C-reactive protein was associated with AF recurrence in Asian studies, whereas not in European studies. Conclusion:Increased pre-ablation level of ANP, BNP, NT-pro-BNP, IL-6, C-reactive protein, LDL, and TIMP-2 was associated with greater risk of AF recurrence after RFCA. 10.1093/europace/euw088
    Body mass index, abdominal fatness, fat mass and the risk of atrial fibrillation: a systematic review and dose-response meta-analysis of prospective studies. Aune Dagfinn,Sen Abhijit,Schlesinger Sabrina,Norat Teresa,Janszky Imre,Romundstad Pål,Tonstad Serena,Riboli Elio,Vatten Lars J European journal of epidemiology Different adiposity measures have been associated with increased risk of atrial fibrillation, however, results have previously only been summarized for BMI. We therefore conducted a systematic review and meta-analysis of prospective studies to clarify the association between different adiposity measures and risk of atrial fibrillation. PubMed and Embase databases were searched up to October 24th 2016. Summary relative risks (RRs) were calculated using random effects models. Twenty-nine unique prospective studies (32 publications) were included. Twenty-five studies (83,006 cases, 2,405,381 participants) were included in the analysis of BMI and atrial fibrillation. The summary RR was 1.28 (95% confidence interval: 1.20-1.38, I = 97%) per 5 unit increment in BMI, 1.18 (95% CI: 1.12-1.25, I = 73%, n = 5) and 1.32 (95% CI: 1.16-1.51, I = 91%, n = 3) per 10 cm increase in waist and hip circumference, respectively, 1.09 (95% CI: 1.02-1.16, I = 44%, n = 4) per 0.1 unit increase in waist-to-hip ratio, 1.09 (95% CI: 1.02-1.16, I = 94%, n = 4) per 5 kg increase in fat mass, 1.10 (95% CI: 0.92-1.33, I = 90%, n = 3) per 10% increase in fat percentage, 1.10 (95% CI: 1.08-1.13, I = 74%, n = 10) per 5 kg increase in weight, and 1.08 (95% CI: 0.97-1.19, I = 86%, n = 2) per 5% increase in weight gain. The association between BMI and atrial fibrillation was nonlinear, p  < 0.0001, with a stronger association at higher BMI levels, however, increased risk was observed even at a BMI of 22-24 compared to 20. In conclusion, general and abdominal adiposity and higher body fat mass increase the risk of atrial fibrillation. 10.1007/s10654-017-0232-4
    Revisiting pulmonary vein isolation alone for persistent atrial fibrillation: A systematic review and meta-analysis. Voskoboinik Aleksandr,Moskovitch Jeremy T,Harel Nadav,Sanders Prashanthan,Kistler Peter M,Kalman Jonathan M Heart rhythm BACKGROUND:Early studies demonstrated relatively low success rates for pulmonary vein isolation (PVI) alone in patients with persistent atrial fibrillation (PeAF). However, the advent of new technologies and the observation that additional substrate ablation does not improve outcomes have created a new focus on PVI alone for treatment of PeAF. OBJECTIVE:The purpose of this study was to systematically review the recent medical literature to determine current medium-term outcomes when a PVI-only approach is used for PeAF. METHODS:An electronic database search (MEDLINE, Embase, Web of Science, PubMed, Cochrane) was performed in August 2016. Only studies of PeAF patients undergoing a "PVI only" ablation strategy using contemporary radiofrequency (RF) technology or second-generation cryoballoon (CB2) were included. A random-effects model was used to assess the primary outcome of pooled single-procedure 12-month arrhythmia-free survival. Predictors of recurrence were also examined and a meta-analysis performed if ≥4 studies examined the parameter. RESULTS:Fourteen studies of 956 patients, of whom 45.2% underwent PVI only with RF and 54.8% with CB2, were included. Pooled single-procedure 12-month arrhythmia-free survival was 66.7% (95% confidence interval [CI] 60.8%-72.2%), with the majority of patients (80.5%) off antiarrhythmic drugs. Complication rates were very low, with cardiac tamponade occurring in 5 patients (0.6%) and persistent phrenic nerve palsy in 5 CB2 patients (0.9% of CB2). Blanking period recurrence (hazard ratio 4.68, 95% CI 1.70-12.9) was the only significant predictor of recurrence. CONCLUSION:A PVI-only strategy in PeAF patients with a low prevalence of structural heart disease using contemporary technology yields excellent outcomes comparable to those for paroxysmal AF ablation. 10.1016/j.hrthm.2017.01.003
    Cryoablation vs. radiofrequency ablation for treatment of paroxysmal atrial fibrillation: a systematic review and meta-analysis. Chen Yi-He,Lu Zhao-Yang,Xiang Yin-,Hou Jian-Wen,Wang Qian,Lin Hui,Li Yi-Gang Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology Aims:Cryoablation is a promising alternative technique to RF ablation for treating paroxysmal AF with encouraging results. However, data about the efficacy and safety comparison between cryoablation and RF ablation is still lacking. Methods and results:We systematically search the PubMed, the Cochrane Library, MEDLINE and Google Scholar databases, and finally identify 16 eligible studies including 7195 patients (2863 for cryoablation; 4332 for RF ablation). Freedom from AF/atrial tachycardial replase is slightly higher in cryoablation than RF ablation during a median 12 months of follow-up, with no statistical significant (RR: 1.05, 95% CI: 0.98-1.13, P = 0.159). In cryoablation, the procedure time is substantially shortened (WMD: -27.66, 95% CI: -45.24 to - 10.08, P = 0.002), whereas the fluoroscopy time is identical to RF ablation (WMD: -0.37, 95% CI: -2.78 to 2.04, P = 0.763). Procedure-related adverse events in cryoablation are parallel with that in RF ablation (RR: 1.08, 95% CI: 0.86-1.35, P = 0.159). Conclusions:Compared with RF ablation, cryoablation present a comparable long-term AF/atrial tachycardial-free survival and procedure-related adverse events. Meanwhile, cryoablation markedly shorten the procedure time, nonetheless, with negligible impact on the fluoroscopy time. 10.1093/europace/euw330
    Warfarin and the Risk of Stroke and Bleeding in Patients With Atrial Fibrillation Receiving Dialysis: A Systematic Review and Meta-analysis. Harel Ziv,Chertow Glenn M,Shah Prakesh S,Harel Shai,Dorian Paul,Yan Andrew T,Saposnik Gustavo,Sood Manish M,Molnar Amber O,Perl Jeffrey,Wald Rachel M,Silver Sam,Wald Ron The Canadian journal of cardiology BACKGROUND:Patients with atrial fibrillation who receive dialysis are at a high risk of ischemic stroke. The role of warfarin in mitigating this risk in patients with atrial fibrillation who receive dialysis is uncertain. Our objective was to examine the safety and efficacy of warfarin in patients who have atrial fibrillation and receive dialysis. METHODS:We used MedLine, Embase, and the Cochrane Library to conduct a systematic review and meta-analysis of published and unpublished observational and interventional studies related to the use of warfarin in patients with atrial fibrillation who receive dialysis, and provided data on the risk of stroke and/or bleeding outcomes relative to placebo or no anticoagulation therapy. A random effects model was used to calculate pooled adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for these outcomes. RESULTS:No randomized controlled trials met the criteria for inclusion. Fourteen observational studies (20,398 participants) were included in the analysis. The use of warfarin was not associated with ischemic stroke (14 studies; 20,398 participants; aHR, 0.77; 95% CI, 0.55-1.07), intracranial hemorrhage (hemorrhagic stroke; 4 studies; 15,726 participants; aHR, 1.93; 95% CI, 0.93-4.00), gastrointestinal bleeding (3 studies; 14,693 participants; aHR, 1.19; 95% CI, 0.8-1.76), or all-cause mortality (7 studies; 16,172 participants; aHR, 0.89; 95% CI, 0.72-1.11). CONCLUSIONS:Observational studies suggest that warfarin was not associated with a clear benefit or harm among patients who have atrial fibrillation and receive dialysis. These estimates were limited by study heterogeneity including the inability to account for a number of important confounders such as the time in the therapeutic range. Because of the high prevalence of atrial fibrillation, stroke, and bleeding complications in this population, well designed clinical trials of warfarin and other anticoagulants are urgently needed. 10.1016/j.cjca.2017.02.004
    Risk of Intraocular Bleeding With Novel Oral Anticoagulants Compared With Warfarin: A Systematic Review and Meta-analysis. Sun Michelle T,Wood Megan K,Chan WengOnn,Selva Dinesh,Sanders Prashanthan,Casson Robert J,Wong Christopher X JAMA ophthalmology Importance:It is unclear if the risk of intraocular bleeding with novel oral anticoagulants differs compared with warfarin. Objective:To characterize the risk of intraocular bleeding with novel oral anticoagulants compared with warfarin. Data Sources:A systematic review and meta-analysis was undertaken in an academic medical setting. MEDLINE and ClinicalTrials.gov were searched for randomized clinical trials published up until August 2016. This search was supplemented by manual bibliography searches of identified trials and other review articles. Study Selection:Studies were eligible for inclusion if they were phase 3 randomized clinical trials, enrolled patients with atrial fibrillation or venous thromboembolism, compared a novel oral anticoagulant (dabigatran, rivaroxaban, apixaban, or edoxaban) with warfarin, and recorded event data on intraocular bleeding. Data on intraocular bleeding were pooled using inverse-variance, weighted, fixed-effects meta-analysis. Data Extraction and Synthesis:The PRISMA guidelines were used for abstracting data and assessing quality. Independent extraction was performed by 2 investigators. Main Outcomes and Measures:Intraocular bleeding events and associated risk ratio for novel oral anticoagulants compared with warfarin. Results:Twelve trials investigating 102 627 patients were included. Randomization to novel oral anticoagulants was associated with a 22% relative reduction in intraocular bleeding compared with warfarin (risk ratio, 0.78; 95% CI, 0.61-0.99). There was no significant heterogeneity observed (I2 = 4.8%, P = .40). Comparably lower risks of intraocular bleeding with novel oral anticoagulants were seen in subgroup analyses, with no significant difference according to the indication for anticoagulation (P for heterogeneity = .49) or the novel oral anticoagulant type (P for heterogeneity = .15). Summary estimates did not differ materially when random-effects meta-analytic techniques were used. Conclusions and Relevance:These results suggest that novel oral anticoagulants reduce the risk of intraocular bleeding by approximately one-fifth compared with warfarin. Similar benefits were seen in both patients with atrial fibrillation and venous thromboembolism. Our data have particular relevance for patients at higher risk of spontaneous retinal and subretinal bleeding. These findings may also have important implications in the perioperative period, in which the use of novel oral anticoagulants may be superior. Future studies are required to better characterize the optimal management of patients with both ophthalmic disease and cardiovascular comorbidities requiring anticoagulation. 10.1001/jamaophthalmol.2017.2199
    Long-term antithrombotic treatment in intracranial hemorrhage survivors with atrial fibrillation. Korompoki Eleni,Filippidis Filippos T,Nielsen Peter B,Del Giudice Angela,Lip Gregory Y H,Kuramatsu Joji B,Huttner Hagen B,Fang Jiming,Schulman Sam,Martí-Fàbregas Joan,Gathier Celine S,Viswanathan Anand,Biffi Alessandro,Poli Daniela,Weimar Christian,Malzahn Uwe,Heuschmann Peter,Veltkamp Roland Neurology OBJECTIVE:To perform a systematic review and meta-analysis of studies reporting recurrent intracranial hemorrhage (ICH) and ischemic stroke (IS) in ICH survivors with atrial fibrillation (AF) during long-term follow-up. METHODS:A comprehensive literature search including MEDLINE, EMBASE, Cochrane library, clinical trials registry was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We considered studies capturing outcome events (ICH recurrence and IS) for ≥3 months and treatment exposure to vitamin K antagonists (VKAs), antiplatelet agents (APAs), or no antithrombotic medication (no-ATM). Corresponding authors provided aggregate data for IS and ICH recurrence rate between 6 weeks after the event and 1 year of follow-up for each treatment exposure. Meta-analyses of pooled rate ratios (RRs) were conducted with the inverse variance method. RESULTS:Seventeen articles met inclusion criteria. Seven observational studies enrolling 2,452 patients were included in the meta-analysis. Pooled RR estimates for IS were lower for VKAs compared to APAs (RR = 0.45, 95% confidence interval [CI] 0.27-0.74, = 0.002) and no-ATM (RR = 0.47, 95% CI 0.29-0.77, = 0.002). Pooled RR estimates for ICH recurrence were not significantly increased across treatment groups (VKA vs APA: RR = 1.34, 95% CI 0.79-2.30, = 0.28; VKA vs no-ATM: RR = 0.93, 95% CI 0.45-1.90, = 0.84). CONCLUSIONS:In observational studies, anticoagulation with VKA is associated with a lower rate of IS than APA or no-ATM without increasing ICH recurrence significantly. A randomized controlled trial is needed to determine the net clinical benefit of anticoagulation in ICH survivors with AF. 10.1212/WNL.0000000000004235
    Atrial fibrillation and the risk for myocardial infarction, all-cause mortality and heart failure: A systematic review and meta-analysis. Ruddox Vidar,Sandven Irene,Munkhaugen John,Skattebu Julie,Edvardsen Thor,Otterstad Jan Erik European journal of preventive cardiology Background In contemporary atrial fibrillation trials most deaths are cardiac related, whereas stroke and bleeding represent only a small subset of deaths. We aimed to evaluate the long-term risk of cardiac events and all-cause mortality in individuals with atrial fibrillation compared to no atrial fibrillation. Design A systematic review and meta-analysis of studies published between 1 January 2006 and 21 October 2016. Methods Four databases were searched. Studies had follow-up of at least 500 stable patients for either cardiac endpoints or all-cause mortality for 12 months or longer. Publication bias was evaluated and random effects models were used to synthesise the results. Heterogeneity between studies was examined by subgroup and meta-regression analyses. Results A total of 15 cohort studies was included. Analyses indicated that atrial fibrillation was associated with an increased risk of myocardial infarction (relative risk (RR) 1.54, 95% confidence interval (CI) 1.26-1.85), all-cause mortality (RR 1.95, 95% CI 1.50-2.54) and heart failure (RR 4.62, 95% CI 3.13-6.83). Coronary heart disease at baseline was associated with a reduced risk of myocardial infarction and explained 57% of the heterogeneity. A prospective cohort design accounted for 25% of all-cause mortality heterogeneity. Due to there being fewer than 10 studies, sources of heterogeneity were inconclusive for heart failure. Conclusions Atrial fibrillation seems to be associated with an increased risk of subsequent myocardial infarction in patients without coronary heart disease and an increased risk of, all-cause mortality and heart failure in patients with and without coronary heart disease. 10.1177/2047487317715769
    Real-World Setting Comparison of Nonvitamin-K Antagonist Oral Anticoagulants Versus Vitamin-K Antagonists for Stroke Prevention in Atrial Fibrillation: A Systematic Review and Meta-Analysis. Ntaios George,Papavasileiou Vasileios,Makaritsis Konstantinos,Vemmos Konstantinos,Michel Patrik,Lip Gregory Y H Stroke BACKGROUND AND PURPOSE:Evidence from the real-world setting complements evidence coming from randomized controlled trials. We aimed to summarize all available evidence from high-quality real-world observational studies about efficacy and safety of nonvitamin-K oral anticoagulants compared with vitamin-K antagonists in patients with atrial fibrillation. METHODS:We searched PubMed and Web of Science until January 7, 2017 for observational nationwide or health insurance databases reporting matched or adjusted results comparing nonvitamin-K oral anticoagulants versus vitamin-K antagonists in patients with atrial fibrillation. Outcomes assessed included ischemic stroke, ischemic stroke or systemic embolism, any stroke or systemic embolism, myocardial infarction, intracranial hemorrhage, major hemorrhage, gastrointestinal hemorrhage, and death. RESULTS:In 28 included studies of dabigatran, rivaroxaban, and apixaban compared with vitamin-K antagonists, all 3 nonvitamin-K oral anticoagulants were associated with a large reduction of intracranial hemorrhage (apixaban hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.31-0.63; dabigatran HR, 0.42; 95% CI, 0.37-0.49; rivaroxaban HR, 0.64; 95% CI, 0.47-0.86); similar rates of ischemic stroke and ischemic stroke or systemic embolism (apixaban HR, 1.05; 95% CI, 0.75-1.19 and HR, 1.08; 95% CI, 0.95-1.22 / dabigatran HR, 0.96; 95% CI, 0.80-1.16 and HR, 1.17; 95% CI, 0.92-1.50 / rivaroxaban HR, 0.89; 95% CI, 0.76-1.04 and HR, 0.73; 95% CI, 0.52-1.04, respectively); apixaban and dabigatran with lower mortality (HR, 0.65; 95% CI, 0.56-0.75 and HR, 0.63; 95% CI, 0.53-0.75, respectively); apixaban with fewer gastrointestinal (HR, 0.63; 95% CI, 0.42-0.95) and major hemorrhages (HR, 0.55; 95% CI, 0.48-0.63); dabigatran and rivaroxaban with more gastrointestinal hemorrhages (HR, 1.20; 95% CI, 1.06-1.36 and HR, 1.24; 95% CI, 1.08-1.41, respectively); dabigatran and rivaroxaban with similar rate of myocardial infarction (HR, 0.96; 95% CI, 0.77-1.21 and HR, 1.02; 95% CI, 0.54-1.89, respectively). CONCLUSIONS:This meta-analysis confirms the main findings of the randomized controlled trials of dabigatran, rivaroxaban, and apixaban in the real-world setting and, hence, strengthens their validity. 10.1161/STROKEAHA.117.017549
    Transcatheter vs Surgical Aortic Valve Replacement for Aortic Stenosis in Low-Intermediate Risk Patients: A Meta-analysis. Tam Derrick Y,Vo Thin Xuan,Wijeysundera Harindra C,Ko Dennis T,Rocha Rodolfo Vigil,Friedrich Jan,Fremes Stephen E The Canadian journal of cardiology BACKGROUND:Transcatheter aortic valve replacement (TAVR) has emerged as the treatment of choice for patients with severe aortic stenosis at high surgical risk; the role of TAVR compared with surgical aortic valve replacement (SAVR) in the low-intermediate surgical risk population remains uncertain. Our primary objective was to determine differences in 30-day and late mortality in patients treated with TAVR compared with SAVR at low-intermediate risk (Society of Thoracic Surgeons Predicted Risk of Mortality < 10%). METHODS:Medline and Embase were searched from 2010 to March 2017 for studies that compared TAVR with SAVR in the low-intermediate surgical risk population, restricted to randomized clinical trials and matched observational studies. Two investigators independently abstracted the data and a random effects meta-analysis was performed. RESULTS:Four randomized clinical trials (n = 4042) and 9 propensity score-matched observational studies (n = 4192) were included in the meta-analysis (n = 8234). There was no difference in 30-day mortality between TAVR and SAVR (3.2% vs 3.1%, pooled risk ratio: 1.02; 95% confidence interval, 0.80-1.30; P = 0.89; I = 0%) or mortality at a median of 1.5-year follow-up (incident rate ratio: 1.01; 95% confidence interval, 0.90-1.15; P = 0.83; I = 0%). There was a higher risk of pacemaker implantation and greater than trace aortic insufficiency in the TAVR group whereas the risk of early stroke, atrial fibrillation, acute kidney injury, cardiogenic shock, and major bleeding was higher in the SAVR group. CONCLUSIONS:Although there was no difference in 30-day and late mortality, the rate of complications differed between TAVR and SAVR in the low-intermediate surgical risk population. 10.1016/j.cjca.2017.06.005
    Risk of Gastrointestinal Bleeding in Patients Taking Non-Vitamin K Antagonist Oral Anticoagulants: A Systematic Review and Meta-analysis. Miller Corey S,Dorreen Alastair,Martel Myriam,Huynh Thao,Barkun Alan N Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association BACKGROUND & AIMS:Non-vitamin K antagonist oral anticoagulants (NOACs) are convenient and effective in the prevention and treatment of venous thromboembolism and the prevention of stroke in patients with atrial fibrillation. However, these drugs have been associated with an increased risk of gastrointestinal (GI) bleeding. We conducted a systematic review and meta-analysis to determine the risk of GI bleeding in patients receiving these drugs. METHODS:We searched the EMBASE, Medline, Cochrane, and ISI Web of knowledge databases through January 2016 for randomized trials that compared NOACs with conventional anticoagulants for approved indications. We conducted a meta-analysis, reporting odds ratios (ORs) with 95% confidence intervals (CIs). The primary outcome was major GI bleeding. Secondary outcomes included clinically relevant nonmajor bleeding and upper and lower GI bleeding. We performed a priori subgroup analyses by individual drug. RESULTS:Our analysis included a total of 43 randomized trials, comprising 166,289 patients. There was no difference between NOACs and conventional anticoagulants in the risk of major bleeding (1.5% vs 1.3%, respectively; OR, 0.98; 95% CI, 0.80-1.21), clinically relevant nonmajor bleeding (0.6% vs 0.6%, respectively; OR, 0.93; 95% CI, 0.64-1.36), upper GI bleeding (1.5% vs 1.6%, respectively; OR, 0.96; 95% CI, 0.77-1.20), or lower GI bleeding (1.0% vs 1.0%, respectively; OR, 0.88; 95% CI, 0.67-1.15). Dabigatran (2.0% vs 1.4%, respectively; OR, 1.27; 95% CI, 1.04-1.55) and rivaroxaban (1.7% vs 1.3%, respectively; OR, 1.40; 95% CI, 1.15-1.70) were associated with increased odds of major GI bleeding compared with conventional anticoagulation, whereas no difference was found for apixaban (0.6% vs 0.7%, respectively; OR, 0.81; 95% CI, 0.64-1.02) or edoxaban (1.9% vs 1.6%, respectively; OR, 0.93; 95% CI, 0.78-1.11). These subgroup findings were not observed in other sensitivity analyses. CONCLUSIONS:In a systematic review and meta-analysis, we found risk of major GI bleeding to be similar between NOACs and conventional anticoagulation. Dabigatran and rivaroxaban, however, may be associated with increased odds of major GI bleeding. Further high-quality studies are needed to characterize GI bleeding risk among NOACs. 10.1016/j.cgh.2017.04.031
    Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation. Baumgartner Christine,da Costa Bruno R,Collet Tinh-Hai,Feller Martin,Floriani Carmen,Bauer Douglas C,Cappola Anne R,Heckbert Susan R,Ceresini Graziano,Gussekloo Jacobijn,den Elzen Wendy P J,Peeters Robin P,Luben Robert,Völzke Henry,Dörr Marcus,Walsh John P,Bremner Alexandra,Iacoviello Massimo,Macfarlane Peter,Heeringa Jan,Stott David J,Westendorp Rudi G J,Khaw Kay-Tee,Magnani Jared W,Aujesky Drahomir,Rodondi Nicolas, Circulation BACKGROUND:Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF. METHODS:We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF. RESULTS:Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4; for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease. CONCLUSIONS:In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF. 10.1161/CIRCULATIONAHA.117.028753
    Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone With Atrial Fibrillation in Patients With Distributive Shock: A Systematic Review and Meta-analysis. McIntyre William F,Um Kevin J,Alhazzani Waleed,Lengyel Alexandra P,Hajjar Ludhmila,Gordon Anthony C,Lamontagne François,Healey Jeff S,Whitlock Richard P,Belley-Côté Emilie P JAMA Importance:Vasopressin is an alternative to catecholamine vasopressors for patients with distributive shock-a condition due to excessive vasodilation, most frequently from severe infection. Blood pressure support with a noncatecholamine vasopressor may reduce stimulation of adrenergic receptors and decrease myocardial oxygen demand. Atrial fibrillation is common with catecholamines and is associated with adverse events, including mortality and increased length of stay (LOS). Objectives:To determine whether treatment with vasopressin + catecholamine vasopressors compared with catecholamine vasopressors alone was associated with reductions in the risk of adverse events. Data Sources:MEDLINE, EMBASE, and CENTRAL were searched from inception to February 2018. Experts were asked and meta-registries searched to identify ongoing trials. Study Selection:Pairs of reviewers identified randomized clinical trials comparing vasopressin in combination with catecholamine vasopressors to catecholamines alone for patients with distributive shock. Data Extraction and Synthesis:Two reviewers abstracted data independently. A random-effects model was used to combine data. Main Outcomes and Measures:The primary outcome was atrial fibrillation. Other outcomes included mortality, requirement for renal replacement therapy (RRT), myocardial injury, ventricular arrhythmia, stroke, and LOS in the intensive care unit and hospital. Measures of association are reported as risk ratios (RRs) for clinical outcomes and mean differences for LOS. Results:Twenty-three randomized clinical trials were identified (3088 patients; mean age, 61.1 years [14.2]; women, 45.3%). High-quality evidence supported a lower risk of atrial fibrillation associated with vasopressin treatment (RR, 0.77 [95% CI, 0.67 to 0.88]; risk difference [RD], -0.06 [95% CI, -0.13 to 0.01]). For mortality, the overall RR estimate was 0.89 (95% CI, 0.82 to 0.97; RD, -0.04 [95% CI, -0.07 to 0.00]); however, when limited to trials at low risk of bias, the RR estimate was 0.96 (95% CI, 0.84 to 1.11). The overall RR estimate for RRT was 0.74 (95% CI, 0.51 to 1.08; RD, -0.07 [95% CI, -0.12 to -0.01]). However, in an analysis limited to trials at low risk of bias, RR was 0.70 (95% CI, 0.53 to 0.92, P for interaction = .77). There were no significant differences in the pooled risks for other outcomes. Conclusions and Relevance:In this systematic review and meta-analysis, the addition of vasopressin to catecholamine vasopressors compared with catecholamines alone was associated with a lower risk of atrial fibrillation. Findings for secondary outcomes varied. 10.1001/jama.2018.4528
    Aetiology of hypospadias: a systematic review of genes and environment. van der Zanden L F M,van Rooij I A L M,Feitz W F J,Franke B,Knoers N V A M,Roeleveld N Human reproduction update BACKGROUND:Hypospadias is a common congenital malformation of the male external genitalia. Most cases have an unknown aetiology, which is probably a mix of monogenic and multifactorial forms, implicating both genes and environmental factors. This review summarizes current knowledge about the aetiology of hypospadias. METHODS:Pubmed was used to identify studies on hypospadias aetiology published between January 1995 and February 2011. Reference lists of the selected manuscripts were also searched to identify additional studies, including those published before 1995. RESULTS:The search provided 922 articles and 169 articles were selected for this review. Studies screening groups of patients with hypospadias for single gene defects found mutations in WT1, SF1, BMP4, BMP7, HOXA4, HOXB6, FGF8, FGFR2, AR, HSD3B2, SRD5A2, ATF3, MAMLD1, MID1 and BNC2. However, most investigators are convinced that single mutations do not cause the majority of isolated hypospadias cases. Indeed, associations were found with polymorphisms in FGF8, FGFR2, AR, HSD17B3, SRD5A2, ESR1, ESR2, ATF3, MAMLD1, DGKK, MID1, CYP1A1, GSTM1 and GSTT1. In addition, gene expression studies indentified CTGF, CYR61 and EGF as candidate genes. Environmental factors consistently implicated in hypospadias are low birthweight, maternal hypertension and pre-eclampsia, suggesting that placental insufficiency may play an important role in hypospadias aetiology. Exogenous endocrine-disrupting chemicals have the potential to induce hypospadias but it is unclear whether human exposure is high enough to exert this effect. Other environmental factors have also been associated with hypospadias but, for most, the results are inconsistent. CONCLUSIONS:Although a number of contributors to the aetiology of hypospadias have been identified, the majority of risk factors remain unknown. 10.1093/humupd/dms002