{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T18:32:00Z","timestamp":1740162720580,"version":"3.37.3"},"reference-count":40,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000},"content-version":"unspecified","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["NIHR204123"],"award-info":[{"award-number":["NIHR204123"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The optimal antithrombotic regimen to reduce the risk of vascular events in patients with peripheral arterial disease (PAD) is contentious. This systematic review and network meta-analysis (NMA) aims to define the relative efficacy and risks of previously investigated antithrombotic medication regimens in preventing major cardiovascular events, vascular limb events and mortality in patients with PAD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and analysis<\/jats:title><jats:p>A peer-reviewed, systematic search will be executed in English on Medline, Embase, Cochrane (CENTRAL), Web of Science and Google Scholar databases in late 2022. The WHO International Clinical Trials Registry platform will also be searched for ongoing trials. Abstracts will be screened independently by two researchers for randomised controlled trials meeting the review criteria. All associated publications including the study protocol will be sought and evaluated together against prespecified inclusion\/exclusion criteria. Two researchers will extract the data into a prepiloted extraction form. Risk-of-bias assessments will be performed using the Cochrane \u2018Risk-of-Bias V.2\u2019 criteria by individuals with domain expertise. All differences will be resolved by consensus or a third individual for ties.<\/jats:p><jats:p>Included trials will be summarised. An NMA will be performed, subject to checks of assumptions. Both primary and secondary outcomes will be analysed on a whole network basis. Pairwise comparisons and league tables will be produced. Prespecified subgroup analyses will include sex, ethnicity, disease status, conservative versus interventional management and key comorbidities. The findings will be evaluated using the Grading of Recommendation Assessment, Development and Evaluation, informed by patient and public involvement work.<\/jats:p><\/jats:sec><jats:sec><jats:title>Ethics and dissemination<\/jats:title><jats:p>This is a systematic review of data in the public domain and does not require ethical approval. Dissemination will include presentations to key vascular and patient organisations, publication in a peer-reviewed journal and an open-access repository of the study data.<\/jats:p><\/jats:sec><jats:sec><jats:title>PROSPERO registration number<\/jats:title><jats:p>CRD42023389262.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bmjopen-2023-072355","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T17:19:50Z","timestamp":1691687990000},"page":"e072355","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Antithrombotic drugs for cardiovascular risk reduction in patients with lower limb peripheral arterial disease: protocol for a systematic review and network meta-analysis of randomised controlled trials"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3455-6659","authenticated-orcid":false,"given":"David Brooke","family":"Sidebottom","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Carradice","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J","family":"Holt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"John-Pierre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9701-8319","authenticated-orcid":false,"given":"Iain Nicholas","family":"Roy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2023,8,10]]},"reference":[{"key":"2023081010152348000_13.8.e072355.1","doi-asserted-by":"crossref","unstructured":"Morley RL , Sharma A , Horsch AD , et al . Peripheral artery disease. BMJ 2018;360. doi:10.1136\/bmj.j5842","DOI":"10.1136\/bmj.j5842"},{"key":"2023081010152348000_13.8.e072355.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2014.12.009"},{"key":"2023081010152348000_13.8.e072355.3","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx095"},{"key":"2023081010152348000_13.8.e072355.4","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1056\/NEJMcp1709326","article-title":"Chronic limb-threatening ischemia","volume":"379","author":"Farber","year":"2018","journal-title":"N Engl J Med"},{"key":"2023081010152348000_13.8.e072355.5","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(19)30255-4"},{"key":"2023081010152348000_13.8.e072355.6","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.303849"},{"key":"2023081010152348000_13.8.e072355.7","unstructured":"Institute for health Metrics and evaluation (IHME) . Global burden of disease. 2019. Available: https:\/\/ghdx.healthdata.org [Accessed 8 Apr 2022]."},{"key":"2023081010152348000_13.8.e072355.8","unstructured":"National clinical guideline centre (UK) . Lower limb peripheral arterial disease: diagnosis and management. London: Royal College of Physicians (UK). National Institute for Health and Clinical Excellence: Guidance, 2012. Available: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK299071\/"},{"key":"2023081010152348000_13.8.e072355.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.04.071"},{"key":"2023081010152348000_13.8.e072355.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.11.008"},{"key":"2023081010152348000_13.8.e072355.11","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-020089"},{"key":"2023081010152348000_13.8.e072355.12","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2015-309076"},{"key":"2023081010152348000_13.8.e072355.13","unstructured":"National Institute for Health and Care Excellence . Peripheral arterial disease: diagnosis and management. clinical guideline [Cg147]. 2012. Available: https:\/\/www.nice.org.uk\/guidance\/cg147 [Accessed 20 Apr 2022]."},{"key":"2023081010152348000_13.8.e072355.14","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0140-6736(17)32409-1","article-title":"Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial","volume":"391","author":"Anand","year":"2018","journal-title":"Lancet"},{"key":"2023081010152348000_13.8.e072355.15"},{"key":"2023081010152348000_13.8.e072355.16","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)09457-3"},{"key":"2023081010152348000_13.8.e072355.17","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199712113372404"},{"key":"2023081010152348000_13.8.e072355.18","first-page":"1488","article-title":"Ticagrelor versus clopidogrel in peripheral artery disease","volume":"376","author":"Patel","year":"2017","journal-title":"N Engl J Med"},{"key":"2023081010152348000_13.8.e072355.19","first-page":"2090","article-title":"Rivaroxaban in peripheral artery disease after Revascularization","volume":"383","author":"Bonaca","year":"2020","journal-title":"N Engl J Med"},{"key":"2023081010152348000_13.8.e072355.20","doi-asserted-by":"publisher","DOI":"10.1583\/13-4275MR.1"},{"key":"2023081010152348000_13.8.e072355.21","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e3181e40dde"},{"key":"2023081010152348000_13.8.e072355.22","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa065959"},{"key":"2023081010152348000_13.8.e072355.23","unstructured":"National Institute for Health and Care Excellence . Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events. technology appraisal guidance [Ta210]. 2010. Available: https:\/\/www.nice.org.uk\/guidance\/ta210 [Accessed 20 Apr 2022]."},{"key":"2023081010152348000_13.8.e072355.24","unstructured":"National Institute for Health and Care Excellence . Rivaroxaban for preventing Atherothrombotic events in people with coronary or peripheral artery disease. Technology appraisal guidance [Ta607]. 2019. Available: https:\/\/www.nice.org.uk\/guidance\/ta607 [Accessed 20 Apr 2022]."},{"key":"2023081010152348000_13.8.e072355.25","unstructured":"Roy I , Sidebottom D . Protocol - systematic review & network meta-analysis of randomised controlled trials comparing Antithrombotic drugs for cardiovascular risk reduction in patients with lower limb peripheral arterial disease. 2022. doi:10.24376\/rd.sgul.21591216.v1"},{"key":"2023081010152348000_13.8.e072355.26","doi-asserted-by":"crossref","unstructured":"Roy I , Sidebottom DB , Holt P , et al . Antithrombotic drugs for cardiovascular risk reduction in patients with lower limb peripheral arterial disease: protocol for a systematic review and network meta-analysis of randomised controlled trials. PROSPERO. 2023. Available: https:\/\/www.crd.york.ac.uk\/prospero\/display_record.php?ID=CRD42023389262 [Accessed 5 Jan 2023].","DOI":"10.1136\/bmjopen-2023-072355"},{"key":"2023081010152348000_13.8.e072355.27","doi-asserted-by":"crossref","unstructured":"Page MJ , McKenzie JE , Bossuyt PM , et al . The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372. doi:10.1136\/bmj.n71","DOI":"10.1136\/bmj.n71"},{"key":"2023081010152348000_13.8.e072355.28","doi-asserted-by":"publisher","DOI":"10.1186\/s13643-020-01542-z"},{"key":"2023081010152348000_13.8.e072355.29","doi-asserted-by":"publisher","DOI":"10.7326\/M14-2385"},{"key":"2023081010152348000_13.8.e072355.30","unstructured":"Joint Formulary Committee . British national Formulary. 2022. Available: http:\/\/www.medicinescomplete.com [Accessed 20 Apr 2022]."},{"key":"2023081010152348000_13.8.e072355.31","unstructured":"Higgins J , Thomas J , Chandler J , et al . Cochrane Handbook for systematic reviews of interventions version (updated Feburary 2022). In: Cochrane Handbook for Systematic Reviews of Interventions. 2022. Available: https:\/\/training.cochrane.org\/handbook [accessed 20 Apr 2022]."},{"key":"2023081010152348000_13.8.e072355.32","unstructured":"Roy I , Sidebottom DB , John-Pierre K . Search strategy - systematic review & network meta-analysis of randomised controlled trials comparing antithrombotic drugs for cardiovascular risk reduction in patients with lower limb peripheral arterial disease. 2023. doi:10.24376\/rd.sgul.21687866"},{"key":"2023081010152348000_13.8.e072355.33","unstructured":"Veritas Health Innovation . Covidence systematic review software. 2022. Available: www.covidence.org [Accessed 20 Apr 2022]."},{"key":"2023081010152348000_13.8.e072355.34","doi-asserted-by":"crossref","unstructured":"Sterne JAC , Savovi\u0107 J , Page MJ , et al . Rob 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019;366. doi:10.1136\/bmj.l4898","DOI":"10.1136\/bmj.l4898"},{"key":"2023081010152348000_13.8.e072355.35","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/jrsm.57","article-title":"Using network meta-analysis to evaluate the existence of small-study effects in a network of interventions","volume":"3","author":"Chaimani","year":"2012","journal-title":"Res Synth Methods"},{"key":"2023081010152348000_13.8.e072355.36","unstructured":"Roy I , Huang C . Analysis plan - systematic review & network meta-analysis of randomised controlled trials comparing antithrombotic drugs for cardiovascular risk reduction in patients with lower limb peripheral arterial disease. 2023. doi:10.24376\/rd.sgul.21688040"},{"key":"2023081010152348000_13.8.e072355.37","unstructured":"R Core Team . R: A language and environment for statistical computing; 2022."},{"key":"2023081010152348000_13.8.e072355.38","unstructured":"R\u00fccker G , Krahn U , K\u00f6nig J , et al . Netmeta: network meta-analysis using frequentist methods. 2022. Available: https:\/\/cran.r-project.org\/package=netmeta"},{"key":"2023081010152348000_13.8.e072355.39","doi-asserted-by":"crossref","unstructured":"Brignardello-Petersen R , Izcovich A , Rochwerg B , et al . GRADE approach to drawing conclusions from a network meta-analysis using a partially Contextualised framework. BMJ 2020;371. doi:10.1136\/bmj.m3907","DOI":"10.1136\/bmj.m3907"},{"key":"2023081010152348000_13.8.e072355.40","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m3731"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2023-072355","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T21:29:18Z","timestamp":1702934958000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2023-072355"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":40,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8,10]]},"published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1136\/bmjopen-2023-072355"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2023-072355","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"type":"print","value":"2044-6055"},{"type":"electronic","value":"2044-6055"}],"subject":[],"published":{"date-parts":[[2023,8]]}}}