{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:10:40Z","timestamp":1792102240407,"version":"4.4.0"},"reference-count":44,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Pharmacologic thromboprophylaxis is widely used for medical inpatients, but its contemporary benefits remain uncertain for clinically relevant venous thromboembolism (VTE).<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate and compare the benefits and risks associated with currently approved in-hospital pharmacologic thromboprophylaxis regimens to prevent symptomatic and clinically relevant VTE and bleeding in acutely ill medical inpatients.<\/jats:p>\n <\/jats:sec>\n \n Data sources<\/jats:title>\n MEDLINE, Embase, Web of Science, and the Cochrane CENTRAL databases were searched until January 31, 2026. Reference lists from retrieved articles and reference literature were also examined.<\/jats:p>\n <\/jats:sec>\n \n Study Selection<\/jats:title>\n Randomized clinical trials that involved adult patients hospitalized for an acute medical illness and compared pharmacologic thromboprophylaxis regimens (low-molecular-weight heparin [LMWH], unfractionated heparin [UHF], and direct oral anticoagulants [DOACs]) with no treatment or placebo were selected.<\/jats:p>\n <\/jats:sec>\n \n Data Extraction and Synthesis<\/jats:title>\n \n Dual independent screening, data extraction, and risk-of-bias assessment were performed. Relative risks (RRs) were pooled using network meta-analyses with random effects. The\n PRISMA<\/jats:ext-link>\n reporting guideline was used.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The effectiveness outcomes were the risk of confirmed symptomatic VTE, clinically relevant VTE, and any VTE. Safety outcomes were mortality, major bleeding, and clinically relevant nonmajor bleeding. Pairwise and network meta-analyses were computed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Among the 22 studies (involving 43\u202f840 patients) included, the 90-day pooled risk of symptomatic VTE was 1.7% (95% CI, 0.6%-4.4%) in the no-treatment group. Compared with no treatment, LMWH was associated with reduced symptomatic VTE risk (RR, 0.68; 95% CI, 0.49-0.94). Point estimates for DOACs (RR, 0.69; 95% CI, 0.36-1.31) and UFH (RR, 0.75; 95% CI, 0.40-1.40) were less than 1, although the results were not statistically significant. LMWH (RR, 0.57; 95% CI, 0.43-0.74), DOACs (RR, 0.58; 95% CI, 0.41-0.82), and UFH (RR, 0.66; 95% CI, 0.45-0.97) were associated with reduced risk of clinically relevant VTE. Using a theoretical conversion rate of asymptomatic into symptomatic VTE, both LMWH and DOACs were associated with decreased risk of symptomatic VTE (RR, 0.63 [95% CI, 0.48-0.83] and 0.66 [95% CI, 0.44-0.99]). DOACs (RR, 2.62; 95% CI, 1.25-5.49) and UFH (RR, 2.33; 95% CI, 1.13-4.79) were associated with an increased risk of major bleeding, compared with no treatment, while LMWH (RR, 1.23; 95% CI, 0.81-1.85) had no association. Mortality was unaffected by the treatment regimens.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this systematic review and network meta-analysis, DOACs, LMWH, and UFH were associated with reduced clinically relevant VTE in medical inpatients; DOACs and UFH had higher risks of major bleeding than LMWH. Proper selection of patients is critical given the overall low absolute risk of VTE.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.11449","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T15:30:19Z","timestamp":1778859019000},"page":"e2611449","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacologic Thromboprophylaxis in Medical Inpatients"],"prefix":"10.1001","volume":"9","author":[{"given":"Christophe","family":"Marti","sequence":"first","affiliation":[{"name":"Division of General Internal Medicine, University Hospitals of Geneva, Geneva, Switzerland"},{"name":"Faculty of Medicine, University of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Righini","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Geneva, Geneva, Switzerland"},{"name":"Division of Angiology and Haemostasis, University Hospitals of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e9goire","family":"Le Gal","sequence":"additional","affiliation":[{"name":"Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Girardi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada"},{"name":"Research Center on Thromboembolic Diseases and Antithrombotic Treatment, Department of Medicine and Surgery, University of Insubria, Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helia","family":"Robert-Ebadi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Geneva, Geneva, Switzerland"},{"name":"Division of Angiology and Haemostasis, University Hospitals of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Combescure","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology, University Hospitals of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Luc","family":"Reny","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine, University Hospitals of Geneva, Geneva, Switzerland"},{"name":"Faculty of Medicine, University of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Blondon","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Geneva, Geneva, Switzerland"},{"name":"Division of Angiology and Haemostasis, University Hospitals of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"issue":"11","key":"zoi260348r1","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1001\/archinte.162.11.1245","article-title":"Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study.","volume":"162","author":"Heit","year":"2002","journal-title":"Arch Intern Med"},{"issue":"2","key":"zoi260348r2","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1177\/003693308102600205","article-title":"Prevention of deep vein thrombosis in medical patients by low-dose heparin.","volume":"26","author":"Belch","year":"1981","journal-title":"Scott Med J"},{"issue":"11","key":"zoi260348r3","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1056\/NEJM197303152881103","article-title":"Small subcutaneous doses of heparin in prevention of venous thrombosis.","volume":"288","author":"Gallus","year":"1973","journal-title":"N Engl J Med"},{"issue":"7","key":"zoi260348r4","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1161\/01.CIR.0000138928.83266.24","article-title":"Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients.","volume":"110","author":"Leizorovicz","year":"2004","journal-title":"Circulation"},{"issue":"7537","key":"zoi260348r5","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1136\/bmj.38733.466748.7C","article-title":"Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial.","volume":"332","author":"Cohen","year":"2006","journal-title":"BMJ"},{"issue":"11","key":"zoi260348r6","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1056\/NEJM199909093411103","article-title":"A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients.","volume":"341","author":"Samama","year":"1999","journal-title":"N Engl J Med"},{"issue":"26","key":"zoi260348r7","doi-asserted-by":"publisher","first-page":"2463","DOI":"10.1056\/NEJMoa1111288","article-title":"Low-molecular-weight heparin and mortality in acutely ill medical patients.","volume":"365","author":"Kakkar","year":"2011","journal-title":"N Engl J Med"},{"key":"zoi260348r8","doi-asserted-by":"publisher","first-page":"7S","DOI":"10.1378\/chest.1412S3","article-title":"American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.","volume":"141","author":"Guyatt","year":"2012","journal-title":"Chest"},{"key":"zoi260348r9","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2022-070022","article-title":"Anticoagulants for thrombosis prophylaxis in acutely ill patients admitted to hospital: systematic review and network meta-analysis.","volume":"378","author":"Eck","year":"2022","journal-title":"BMJ"},{"issue":"8","key":"zoi260348r10","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2200332","article-title":"Enoxaparin versus placebo to prevent symptomatic venous thromboembolism in hospitalized older adult medical patients.","volume":"2","author":"Mottier","year":"2023","journal-title":"NEJM Evid"},{"issue":"1","key":"zoi260348r11","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1161\/01.STR.32.1.262","article-title":"Venous thromboembolism after acute stroke.","volume":"32","author":"Kelly","year":"2001","journal-title":"Stroke"},{"key":"zoi260348r12","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2021-069590","article-title":"Risks of deep vein thrombosis, pulmonary embolism, and bleeding after COVID-19: nationwide self-controlled cases series and matched cohort study.","volume":"377","author":"Katsoularis","year":"2022","journal-title":"BMJ"},{"issue":"5","key":"zoi260348r13","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.019459","article-title":"Association between asymptomatic proximal deep vein thrombosis and mortality in acutely ill medical patients.","volume":"10","author":"Raskob","year":"2021","journal-title":"J Am Heart Assoc"},{"issue":"11","key":"zoi260348r14","doi-asserted-by":"publisher","first-page":"2119","DOI":"10.1111\/jth.13140","article-title":"Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH.","volume":"13","author":"Kaatz","year":"2015","journal-title":"J Thromb Haemost"},{"issue":"23","key":"zoi260348r15","first-page":"I22","article-title":"Natural history of venous thromboembolism.","volume":"107","author":"Kearon","year":"2003","journal-title":"Circulation"},{"issue":"6","key":"zoi260348r16","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1111\/jth.13677","article-title":"Anticoagulation in patients with isolated distal deep vein thrombosis: a meta-analysis.","volume":"15","author":"Franco","year":"2017","journal-title":"J Thromb Haemost"},{"issue":"24","key":"zoi260348r17","doi-asserted-by":"publisher","first-page":"IV13","DOI":"10.1161\/01.CIR.0000150640.98772.af","article-title":"Preventing venous thromboembolism in medical patients.","volume":"110","author":"Leizorovicz","year":"2004","journal-title":"Circulation"},{"key":"zoi260348r18","doi-asserted-by":"publisher","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials.","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"zoi260348r19","doi-asserted-by":"publisher","first-page":"f2914","DOI":"10.1136\/bmj.f2914","article-title":"Demystifying trial networks and network meta-analysis.","volume":"346","author":"Mills","year":"2013","journal-title":"BMJ"},{"key":"zoi260348r20","doi-asserted-by":"publisher","first-page":"j3932","DOI":"10.1136\/bmj.j3932","article-title":"Multivariate and network meta-analysis of multiple outcomes and multiple treatments: rationale, concepts, and examples.","volume":"358","author":"Riley","year":"2017","journal-title":"BMJ"},{"key":"zoi260348r21","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s12874-015-0060-8","article-title":"Ranking treatments in frequentist network meta-analysis works without resampling methods.","volume":"15","author":"R\u00fccker","year":"2015","journal-title":"BMC Med Res Methodol"},{"issue":"7454","key":"zoi260348r22","doi-asserted-by":"publisher","first-page":"1490","DOI":"10.1136\/bmj.328.7454.1490","article-title":"Grading quality of evidence and strength of recommendations.","volume":"328","author":"Atkins","year":"2004","journal-title":"BMJ"},{"issue":"2","key":"zoi260348r23","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1111\/j.0006-341X.2000.00455.x","article-title":"Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis.","volume":"56","author":"Duval","year":"2000","journal-title":"Biometrics"},{"issue":"6","key":"zoi260348r24","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1177\/000331978803900603","article-title":"Prevalence and prevention of deep venous thrombosis of the lower extremities in high-risk pulmonary patients.","volume":"39","author":"Ibarra-P\u00e9rez","year":"1988","journal-title":"Angiology"},{"issue":"12","key":"zoi260348r26","first-page":"567","article-title":"Calcium nadroparin in the prevention of thromboembolic disease in elderly subjects. Study of tolerance.","volume":"24","author":"Forette","year":"1995","journal-title":"Presse Med"},{"issue":"9012","key":"zoi260348r27","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1016\/S0140-6736(96)91009-0","article-title":"Randomised, controlled trial of low-dose heparin for prevention of fatal pulmonary embolism in patients with infectious diseases. The Heparin Prophylaxis Study Group.","volume":"347","author":"G\u00e4rdlund","year":"1996","journal-title":"Lancet"},{"key":"zoi260348r28","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1159\/000217272","article-title":"The venous thrombotic risk in non-surgical patients: epidemiological data and efficacy\/safety profile of a low-molecular-weight heparin (enoxaparin).","volume":"26","author":"Lechler","year":"1996","journal-title":"Haemostasis"},{"issue":"3","key":"zoi260348r29","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1159\/000217198","article-title":"Subcutaneous low-molecular-weight heparin versus standard heparin and the prevention of thromboembolism in medical inpatients.","volume":"26","author":"Harenberg","year":"1996","journal-title":"Haemostasis"},{"issue":"4","key":"zoi260348r30","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1067\/mhj.2003.189","article-title":"Randomized comparison of enoxaparin with unfractionated heparin for the prevention of venous thromboembolism in medical patients with heart failure or severe respiratory disease.","volume":"145","author":"Kleber","year":"2003","journal-title":"Am Heart J"},{"issue":"5-6","key":"zoi260348r31","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1007\/s00228-005-0944-3","article-title":"Lack of effect of a low-molecular-weight heparin (nadroparin) on mortality in bedridden medical in-patients: a prospective randomised double-blind study.","volume":"61","author":"Mah\u00e9","year":"2005","journal-title":"Eur J Clin Pharmacol"},{"issue":"1","key":"zoi260348r32","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.amjmed.2005.03.049","article-title":"The prophylaxis of medical patients for thromboembolism pilot study.","volume":"119","author":"Lederle","year":"2006","journal-title":"Am J Med"},{"issue":"6","key":"zoi260348r34","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1111\/j.1538-7836.2010.03848.x","article-title":"A randomized, double-blind study of certoparin vs. unfractionated heparin to prevent venous thromboembolic events in acutely ill, non-surgical patients: CERTIFY Study.","volume":"8","author":"Riess","year":"2010","journal-title":"J Thromb Haemost"},{"issue":"18","key":"zoi260348r35","doi-asserted-by":"publisher","first-page":"2953","DOI":"10.1517\/14656566.2010.521498","article-title":"An open-label comparison of the efficacy and safety of certoparin versus unfractionated heparin for the prevention of thromboembolic complications in acutely ill medical patients: CERTAIN.","volume":"11","author":"Schellong","year":"2010","journal-title":"Expert Opin Pharmacother"},{"issue":"23","key":"zoi260348r36","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.1056\/NEJMoa1110899","article-title":"Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients.","volume":"365","author":"Goldhaber","year":"2011","journal-title":"N Engl J Med"},{"issue":"20","key":"zoi260348r37","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1056\/NEJMoa1111096","article-title":"Rivaroxaban for thromboprophylaxis in acutely ill medical patients.","volume":"368","author":"Cohen","year":"2013","journal-title":"N Engl J Med"},{"issue":"12","key":"zoi260348r38","first-page":"882","article-title":"Randomised controlled trial for efficacy of unfractionated heparin (UFH) versus low molecular weight heparin (LMWH) in thrombo-prophylaxis.","volume":"61","author":"Ishi","year":"2013","journal-title":"J Assoc Physicians India"},{"issue":"4","key":"zoi260348r39","doi-asserted-by":"publisher","first-page":"278","DOI":"10.7326\/0003-4819-146-4-200702200-00007","article-title":"Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients.","volume":"146","author":"Dentali","year":"2007","journal-title":"Ann Intern Med"},{"key":"zoi260348r40","doi-asserted-by":"publisher","first-page":"e185S","DOI":"10.1378\/chest.11-2289","article-title":"Approach to outcome measurement in the prevention of thrombosis in surgical and medical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.","volume":"141","author":"Guyatt","year":"2012","journal-title":"Chest"},{"issue":"5","key":"zoi260348r41","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD003747.pub4","article-title":"Heparin for the prevention of venous thromboembolism in acutely ill medical patients (excluding stroke and myocardial infarction).","volume":"2014","author":"Alikhan","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"issue":"19","key":"zoi260348r42","doi-asserted-by":"publisher","first-page":"4929","DOI":"10.1182\/bloodadvances.2020002482","article-title":"Risk-assessment models for VTE and bleeding in hospitalized medical patients: an overview of systematic reviews.","volume":"4","author":"Darzi","year":"2020","journal-title":"Blood Adv"},{"key":"zoi260348r43","doi-asserted-by":"publisher","first-page":"e1S","DOI":"10.1378\/chest.11-2290","article-title":"Patient values and preferences in decision making for antithrombotic therapy: a systematic review: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.","volume":"141","author":"MacLean","year":"2012","journal-title":"Chest"},{"issue":"6","key":"zoi260348r44","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1111\/jth.13687","article-title":"A decision model to estimate a risk threshold for venous thromboembolism prophylaxis in hospitalized medical patients.","volume":"15","author":"Le","year":"2017","journal-title":"J Thromb Haemost"},{"key":"zoi260348r25","first-page":"51","volume-title":"Fraxiparine: Second International Symposium Recent Pharmacological and Clinical Data","author":"Aquino","year":"1990"},{"key":"zoi260348r33","unstructured":"Dalteparin vs unfractionated heparin for the prevention of venous thromboembolism (VTE) in hospitalized acutely ill medical patients. ClinicalTrials.gov identifier: NCT00445328. Updated October 15, 2009. Assessed January 2026. https:\/\/clinicaltrials.gov\/study\/NCT00445328"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2849101\/marti_2026_oi_260348_1782848499.92251.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T21:03:35Z","timestamp":1782853415000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2849101"}},"subtitle":["A Systematic Review and Network Meta-Analysis"],"short-title":[],"issued":{"date-parts":[[2026,5,15]]},"references-count":44,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2026.11449","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,15]]}}}