© Schattauer 2013 Thrombosis and Haemostasis 109.4/2013 1 Review Article Should all acutely ill medical patients be treated with antithrombotic drugs? A review of the interventional trials Francesco Violi; Ludovica Perri; Lorenzo Loffredo Divisione I Clinica medica, Policlinico Umberto I, Sapienza University, Rome, Italy Summary After reports from observational studies suggesting an association be- tween acutely ill medical patients and venous thromboembolism (VTE), interventional trials with anticoagulants drugs have demon- strated a significant reduction of VTE during and immediately after hospitalisation. Although several guidelines suggest the clinical rel- evance of reducing this outcome, there is a low tendency to use anti- coagulants in patients hospitalised for acute medical illness. We speculated that such underuse may be dependent on a low perception that patients included in the trials are actually at risk of thromboem- bolism. Therefore, the aim of this study was to analyse the clinical set- tings included in the interventional trials and their relationship with thrombotic risk. Analysis of interventional trials revealed that the ma- jority of patients included in the trials (about 80%) were affected by heart failure, acute respiratory syndrome or infections. Among these three illnesses, literature data shows an association with venous thrombosis only in patients with acute infections; this finding was, however, supported only by retrospective study. On the contrary, there is scarce or no evidence that heart failure and acute respiratory syn- drome are associated with venous thrombosis. These data underscore the need of better defining the thrombotic risk profile of acutely ill medical patients included in interventional trials with anticoagulants. Keywords Venous thrombosis, anticoagulants, medical patients Correspondence to: Prof. Francesco Violi Divisione I Clinica Medica Viale del Policlinico 155 Roma, 00161, Italy Tel.: +39 064461933, Fax: +39 0649970103 E-mail: francesco.violi@uniroma1.it Received: November 23, 2012 Accepted after major revision: January 9, 2013 Prepublished online: February 21, 2013 doi:10.1160/TH12-11-0860 Thromb Haemost 2013; 109: ■■■■ Introduction Epidemiological studies have provided evidence of a high rate of thromboembolism in patients hospitalised in medical wards (1-3). Based on this, several clinical trials with anticoagulants including low-molecular-weight heparin (LMWH) and fondaparinux have been performed in patients hospitalised for acute medical illness to prevent thromboembolism (4-12). Interventional trials consistently showed that prophylaxis with anticoagulants reduces the risk of composite endpoints of deep venous thrombosis (DVT), pulmonary embolism (PE) and DVT-related death. These results prompted rec- ommendation to the use anticoagulant prophylaxis in patients hos- pitalised for acute medical illness (13), but, despite this, there is a widespread underuse of anticoagulant prophylaxis in the medical wards of hospitals (14). This issue has been underscored by recent reviews, which, however, did not take into account the relationship between each clinical setting included in the interventional trials and the relative thrombotic risk in this setting (15-17). Thus, compared to other clinical models in interventional trials with anticoagulants, acute medical illness represents an extremely heterogeneous setting with potentially wide range of thrombotic risk. Hence, it is possible that the perception of thromboembolism risk varies according to the clinical presentation and that the pro- phylactic approach is influenced by the severity of disease. This ar- gument could imply that clinical settings included in the interven- tional trials may carry a different thrombotic risk, but so far this issue has been only explored in part. Therefore, the aim of this study was to analyse the population included in the interventional trials and to discuss whether a different thrombotic risk may be re- sult from the typology of acute medical illness. Methods Eligibility criteria • Types of studies: Randomised clinical trials (RCTs) studying the effect of thromboembolism prophylaxis in medical patients. No language, publication date, or publication status restrictions were imposed. • Types of intervention: Trials comparing the beneficial and harmful effects of antithrombotic drugs (LMWH and fonda- parinux) vs. placebo. For personal or educational use only. No other uses without permission. All rights reserved. Note: Uncorrected proof, prepublished online Downloaded from www.thrombosis-online.com on 2013-03-23 | ID: 76748 | IP: 95.235.10.250