ALBERT

Description: Key Points The incidence of venous thromboembolism is high in patients with a solid tumor and implanted port in the real-life practice setting. The risk factors for catheter-related thrombosis differ from those for venous thromboembolism unrelated to the catheter.

Description: Key Points Symptomatic extensions, whether or not reaching the SFJ, are common complications of SVT. Their frequency and associated risk of venous thromboembolic complications and medical resource consumption are reduced by fondaparinux.

Description: Background We examined data from acutely ill medical patients enrolled in The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) to determine factors that are independently associated with an increased risk of bleeding during hospitalization. Methods Patients ≥18 years old, hospitalized for ≥3 days with an acute medical illness have been enrolled consecutively since July 2002. Exclusion criteria are: therapeutic antithrombotics/thrombolytics at admission; major surgery or trauma during 3 months prior to admission; and venous thromboembolism (VTE) treatment within 24 hours of admission. Patients with bleeding immediately prior to, or at admission were excluded from this analysis. Factors considered were: age, ICU stay, reduced creatinine clearance, severe infection, cerebrovascular stroke, cancer, diabetes, severe renal failure, hypertension, lower limb paralysis, bleeding disorders, hemorrhagic stroke, thrombocytopenia, gastro-duodenal ulcer, hepatic failure, central venous catheter at admission, hormonal therapy for cancer, platelet count, BMI, immobility, and length of hospital stay. Factors increasing the risk of bleeding were identified by univariate analysis (P≤0.20) and included in a multiple logistic regression model. Factors with significance of P≤0.05 were retained in the model. Bleeding events were defined as major or clinically significant non-major according to published criteria (Büller HR et al. N Engl J Med.2003;349:1695–702). Results . Data were from 2816 patients enrolled up to 30 June 2004 in 34 hospitals in 10 countries. Patients were: 48% female, mean age 64 years, mean weight 72 kg, mean length of hospital stay 12 days, and 37% were immobile for ≥3 days (median duration of immobility 6 days, including immobility immediately prior to admission). Only 89 (3.2%) patients had in-hospital bleeding: 1.2% major, 1.9% clinically significant non-major, 0.1% unspecified. Factors that were independently associated with an increased risk of bleeding (major or non-major) in acutely ill medical patients are shown in Table 1. Conclusion Only 3.2% of acutely ill medical patients in IMPROVE had in-hospital bleeding. Major bleeding (1.2%) was similar to that observed in a major clinical trial on VTE prophylaxis, MEDENOX (1.0%; Samama et al. N Engl J Med.1999;341:793–800). Advanced age, contrary to the belief of many physicians, was not independently associated with an increased risk of bleeding. Final results will be presented with adjustment for the influence of VTE prophylaxis and antiplatelet drugs. Table 1. Factors independently associated with an increased risk of bleeding in acutely ill medical patients Factor OR 95% CI *compared with creatinine clearance 〉60 mL/min (normal renal function) Bleeding disorder 8.38 3.53–19.90 Active gastro-duodenal ulcer 4.26 1.86–9.76 Hepatic failure 2.97 1.26–6.96 Creatinine clearance

Description: Abstract 171 Introduction: SVT is a common disease, associated with risks of clinically relevant venous thromboembolic complications. Currently, treatment of isolated SVT (i.e. without concomitant deep-vein thrombosis, DVT, or pulmonary embolism, PE) is based on analgesic agents, topical or oral nonsteroidal anti-inflammatory drugs, elastic stockings and occasionally surgery. Previous clinical trials have suggested the benefit of an extended antithrombotic therapy. Yet the optimal antithrombotic treatment remains unknown. Fondaparinux (Arixtra®) is a synthetic selective inhibitor of factor Xa with a favorable benefit-risk profile in the prevention and treatment of venous and arterial thrombosis in various medical and surgical settings. The large-scale, double-blind, randomized, placebo-controlled, CALISTO trial was designed to evaluate the benefit-risk ratio of fondaparinux 2.5 mg subcutaneously once daily during 45 days in 3000 patients with symptomatic, isolated SVT of the lower limbs documented by compression ultrasound (CUS). Methods: The study concerned male or female patients 18 years of age or greater with acute symptomatic isolated SVT of the lower limbs at least 5 cm long documented by standard CUS. After randomization (Day 1), subjects received fondaparinux 2.5 mg or placebo subcutaneously once daily up to Day 45. Study treatments were administered on an outpatient basis. Follow-up continued up to Day 75. Permitted medications included analgesic agents, topical non-steroidal anti-inflammatory drugs, graduated compression (elastic) stockings, aspirin at low dose (up to 325 mg per day) and other oral antiplatelet agents if the subject was receiving these drugs at the time of screening for a chronic medical condition. The primary efficacy outcome was confirmed symptomatic thromboembolic complications (a composite of PE, DVT, extension of SVT with thrombus head ≤3 cm from the saphenofemoral junction or recurrence of SVT) or all-cause death up to Day 45. Safety outcomes included major bleeding, clinically relevant non-major bleeding and death. All efficacy and safety outcomes were adjudicated by a central adjudication committee, unaware of treatment assignment. Results: The study started in March 2007 and inclusions were completed on May 15th 2009, with the recruitment of 3002 patients. The follow-up of the last patient was completed on July 31st 2009. Overall, on blinded preliminary data available on June 23rd 2009 (n=2994), the median age of patients was 58 [range: 19-92] years; 63.9% were women; 37.0% were obese (BMI ≥30 kg/m2). The main predisposing risk factors for SVT were varicose veins (88.6%) and a history of SVT (11.9%). More than one SVT was observed on baseline CUS in 19.2% of patients. The qualifying SVT predominantly involved the great saphenous vein alone (64.6% of patients). At Day 45, the overall incidence of adjudicated and adjudicated-pending symptomatic thromboembolic complications or death was 4.4% (Table). There was one adjudicated major bleeding. The final results according to treatment groups will be presented during the congress. Conclusions: There is an unmet medical need for an evidence-based anticoagulant treatment for isolated SVT. CALISTO is the first large randomized, controlled trial designed to establish standard anticoagulant therapy in patients with isolated SVT. It also provides a large database on the clinical characteristics of this disease. Disclosures: Décousus: GSK: Consultancy, Research Funding. Leizorovicz:GSK: Consultancy.

Description: Background: Patients with a first episode of unprovoked pulmonary embolism have a high risk of recurrent venous thromboembolism (VTE) after anticoagulation is discontinued. Prolongation of anticoagulant therapy beyond the initial period of 3 to 6 months is associated with a significant reduction of recurrent VTE, but an excess of bleeding events. In addition, most studies assessing prolonged treatment did not follow the patients after treatment had been stopped. Thus, the optimal duration of anticoagulation in patients with a first unprovoked pulmonary embolism remains uncertain. Method: In a multicenter, randomized, double-blind, controlled trial, we compared an additional 18 months of warfarin (target International Normalized Ratio, 2 to 3) with placebo in patients with a first episode of unprovoked pulmonary embolism that had been initially treated with a vitamin K antagonist for 6 uninterrupted months. In both groups, all patients were followed up for an additional median period of 2 years after treatment had been stopped. Primary outcome was the composite of recurrent VTE or major bleeding during the 18-month treatment period. Secondary outcomes included the composite outcome during the entire study period (i.e. 18 months plus a median follow-up of 2 years), deaths not caused by pulmonary embolism or major bleeding and the components of the composite outcome during the treatment period and during the entire study period. All outcomes were centrally adjudicated. Results: A total of 371 patients were included in the study and analyzed on an intention-to-treat basis. During the treatment period, the composite outcome occurred in 6 of 184 patients (3.3%) in the warfarin group and in 25 of 187 patients (13.5%) in the placebo group (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.09-0.55; p=0.0004). Recurrent VTE occurred in 3 (1.7%) patients in the warfarin group and in 25 (13.5%) in the placebo group (HR, 0.11; 95%CI, 0.03-0.37); major bleeding occurred in 4 (2.2%) patients in the warfarin group and in 1 (0.5%) in the placebo group (HR, 4.07; 95%CI, 0.45-36.38). Two deaths not related to the study outcome occurred in each group. During the entire median study period of 41 months, the composite outcome occurred in 33 (20.8%) patients in the warfarin group and in 41 (23.5%) in the placebo group (HR, 0.76; 95%CI, 0.48-1.20; p=0.24) (Figure 1). Recurrent VTE occurred in 28 (17.9%) patients in the warfarin group and in 39 (22.1%) in the placebo group (HR, 0.67; 95%CI, 0.41-1.08); major bleeding occurred in 6 (3.5%) patients in the warfarin group and in 4 (2.5%) in the placebo group (HR, 1.57; 95%CI, 0.44-5.55). Thirteen (11.9%) patients died in the warfarin group, four deaths being related to recurrent VTE and one to major bleeding; six (3.6%) patients died in the placebo group from a cause unrelated to recurrent VTE or bleeding (p=0.08). Of the 67 episodes of recurrent VTE, 52 (77.6%) were pulmonary embolism and 58 (86.6%) were unprovoked. Conclusion: After 6 months of anticoagulation for a first episode of unprovoked pulmonary embolism, extending anticoagulation for an additional 18 months was associated with a major reduction in the risk of recurrent VTE or major bleeding during the treatment period. However, this benefit was not maintained after discontinuation of anticoagulation. (ClinicalTrials.gov number NCT00740883). Figure 1. Cumulative risk of the composite outcome (recurrent VTE or major bleeding) over the entire study period Figure 1. Cumulative risk of the composite outcome (recurrent VTE or major bleeding) over the entire study period Disclosures Couturaud: Astra Zeneka: Co-investigator in clinical trial, Co-investigator in clinical trial Other, Membership on an entity's Board of Directors or advisory committees; Bayer: Co-investigator in clinical trial Other, Membership on an entity's Board of Directors or advisory committees. Sanchez:Bayer: Membership on an entity's Board of Directors or advisory committees. Mismetti:Bayer: Membership on an entity's Board of Directors or advisory committees; pfizer: Membership on an entity's Board of Directors or advisory committees; boerhinger ingelheim: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. Jego:Bayer: Membership on an entity's Board of Directors or advisory committees; actelion: Research Funding; GlaxoSmithKline: Research Funding. Parent:Bayer: Membership on an entity's Board of Directors or advisory committees. Lorillon:Astra Zeneka: Membership on an entity's Board of Directors or advisory committees, symposium invitation Other; Sanofi: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Girard:Leo Pharma: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Lacut:Bayer-Healthcare: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Boehringer Ingelheim: Research Funding. Leroyer:Novartis: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Investigator in COPD clinical trials, Investigator in COPD clinical trials Other, Membership on an entity's Board of Directors or advisory committees; Astra Zeneka: Investigator in asthma clinical trials Other, Membership on an entity's Board of Directors or advisory committees. Decousus:Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Meyer:Sanofi-Aventis: Research Funding; LEO Pharma: Research Funding; Bayer: Research Funding; Boehringer Ingelheim: Research Funding. Mottier:Pfizer: Membership on an entity's Board of Directors or advisory committees; bayer: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding.

Description: Introduction: Findings from the recent EXCLAIM study demonstrate that selected acutely ill medical patients with reduced mobility benefit from extended-duration enoxaparin venous thromboembolism (VTE) prophylaxis (Blood2007;110:1862). However, it is unknown whether the EXCLAIM population is representative of acutely ill medical patients admitted to hospitals worldwide. In this subanalysis, we assessed whether the EXCLAIM population was representative of the medical patients enrolled in the multinational IMPROVE (Chest2007;132:936–45) and ENDORSE (Lancet2008;371:387–94) registries known to be at risk for VTE. Methods: Using patient data from IMPROVE and ENDORSE, we applied the EXCLAIM eligibility criteria to a representative, multinational population of acutely ill medical patients at risk for VTE. The IMPROVE and ENDORSE studies assessed VTE-risk and prophylaxis use of enrolled patients according to the 2004 American College of Chest Physicians (ACCP) guidelines (Chest2004;126:338S–400S). ACCP criteria for VTE risk were met in 46% (6,907/15,156) of IMPROVE and 43% (15,487/36,351) of ENDORSE study patients (Chest2007;132:936–45; Lancet2008;371:387–94). The EXCLAIM eligibility criteria required patients to be confined to total bed rest (level 1 immobility), or bed rest with bathroom privileges (level 2 immobility) and have at least 1 of 3 predefined risk factors for VTE (i.e., age 〉 75 years; history of VTE; active or prior cancer). Results: EXCLAIM eligibility criteria were met in 30% (2,072/6,907) IMPROVE and 36% (5,535/15,487) ENDORSE medical patients considered at risk for VTE by ACCP. During hospitalization, ACCP-recommended prophylaxis was provided to 69% (1,426/2,072) and 46% (2,548/5,535) of EXCLAIM-eligible patients enrolled in IMPROVE and ENDORSE, respectively. Following discharge from hospital (median length of stay 5 days for US, 8 days for non-US), only 9% (153/1,719) of EXCLAIM-eligible patients in the IMPROVE study received any type of ACCP-recommended VTE prophylaxis. Conclusions: Evidence from the EXCLAIM study demonstrated that the benefit-to-risk ratio in selected hospitalized medical patients favors the use of prolonged VTE prophylaxis. This population corresponds to one in three of the representative hospitalized patients with acute medical illness enrolled in IMPROVE and ENDORSE. Data on prophylaxis use from the IMPROVE registry suggest that only 9% of such patients are currently receiving optimal VTE prophylaxis following hospital discharge.

Description: INTRODUCTION Women with a history of venous thromboembolism (VTE) have a 2% to 10% absolute risk of developing pregnancy-associated recurrent VTE. Based on these figures, current guidelines recommend postpartum thromboprophylaxis in all pregnant women with a history of VTE. Women with a moderate or high risk of recurrent VTE (i.e. women with a history of VTE that is either unprovoked or associated with a hormonal or minor risk factor), should also receive thromboprophylaxis antepartum. The optimal dose of low-molecular-weight heparin (LMWH) for thromboprophylaxis in pregnant women at moderate or high risk of recurrent VTE is currently unknown, as only two very small prospective trials, both with methodological limitations, have evaluated pharmacological prevention of recurrent VTE in this population. Therefore, the major international guidelines suggest the use of either a prophylactic or intermediate (half-therapeutic) dose of LMWH in this setting, without a preference of one dose over the other. The Highlow study is an investigator-initiated, multicenter, international, open-label, randomized controlled trial (RCT) that compares the efficacy and safety of a fixed dose of LMWH versus an intermediate dose of LMWH for the prevention of pregnancy-associated recurrent VTE (NCT 01828697; www.highlowstudy.org). The rationale and design features of the Highlow study were recently published [Bleker SM, Thromb Res, 2016]. Here, we present an interim report. METHODS In April 2013, we enrolled the first patient in the Highlow study. For the current report, we analyzed the enrolment rates and baseline characteristics of patients in the Highlow study between 1 April 2013 and 28 June 2016. Twelve centers recorded eligible women that did not give informed consent. Using the enrolment data from these centers, we analyzed the percentage of women giving informed consent, and reasons for not giving consent. All characteristics were summarized using descriptive statistics. RESULTS A total of 222 pregnant patients with a history of VTE that fitted the in- and exclusion criteria of the Highlow study were enrolled in 43 centers in 5 countries (Figure 1). The inclusion rate has been growing exponentially over time (Figure 2). In 12 centers that recorded eligible women not giving consent, 101 of 149 identified patients gave informed consent (68%). Patients who declined participation either did not give a specific reason (N=22; 46%), preferred a low dose of LMWH (N=20; 42%), preferred an intermediate dose (N=2; 4%), preferred a therapeutic dose (N=2; 4%), refused antepartum prophylaxis (N=1; 2%) or had been advised by another physician not to participate (N=1; 2%). On 28 June 2016, baseline data in the CRF had been completed for 181 patients. Six patients participated twice. The mean age was 33 years ± 5.1, with a mean body mass index of 26.7 ± 5.9. The majority had a history of lower limb deep vein thrombosis (N=102; 56%) or pulmonary embolism (N=72, 40%). Of all previous VTE, the majority was hormone-related (N=97; 54%) or related to pregnancy (N=58; 32%). In total, 34 (19%) of prior VTE were unprovoked, and in only 19 cases (11%) a minor risk factor had been present. Thrombophilia screening had been performed previously in 101 patients (56%) and more than half of them (59 patients, 58%) had positive tests, especially for heterozygous factor V Leiden (N=39; 64%) and the heterozygous prothrombin 20210A mutation (N=13; 22%). CONCLUSIONS This report represents the largest number of pregnant women with a history of VTE participating in a RCT to date, and the future results are very likely to impact current clinical practice and consensus guidelines. Reassuringly, our enrolment rate shows that recruitment of pregnant women with a history of VTE is feasible. With the current enrolment rate we expect to include the last patient, reaching the event-driven sample size of approximately a 1000 patients, by the end of 2019. Hence, the outcome results can be expected in 2020. SPONSORSHIP AND FINANCIAL SUPPORT An unrestricted grant is provided by Aspen Pharma to the Academic Medical Center in Amsterdam (the Netherlands), who is the sponsor of the Highlow study. In France, where CHU de Saint Etienne is the sponsor, a grant was acquired from the French Ministry of Health (PHRC national 2014). Figure 1 NUMBER OF ENROLLED PATIENTS FROM APRIL 2013 TO JUNE 2016 Figure 1. NUMBER OF ENROLLED PATIENTS FROM APRIL 2013 TO JUNE 2016 Figure 2 NUMBER OF INCLUSIONS PER QUARTILE Figure 2. NUMBER OF INCLUSIONS PER QUARTILE Disclosures Buchmüller: French Ministry of Health: Research Funding. Chauleur:Sanofi: Honoraria; French Ministry of Health: Research Funding. Ní Áinle:Actelion UK: Research Funding. Verhamme:Boehringer Ingelheim: Honoraria, Research Funding; Bayer-Healthcare: Honoraria, Research Funding; Pfizer: Honoraria; Sanofi-Aventis: Honoraria, Research Funding; LeoPharma: Research Funding; Daiichi-Sankyo: Honoraria. Décousus:French Ministry of Health: Research Funding.

Description: Background Without evidence from autopsies, the majority of deaths resulting from pulmonary emboli (PE) are indistinguishable from deaths due to other cardiovascular diseases. This has led to a gap in perceptions between the benefits and risks of providing venous thromboembolism (VTE) prophylaxis. In this study, we estimated the incidence of clinically apparent VTE in hospitalized acutely ill medical patients in The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE), and compared this with the expected incidence derived from clinical studies that used autopsy or prospective venographic confirmation of clinically important VTE. Methods Beginning in July 2002, a consecutive, unselected sample of patients who were aged ≥18 years and hospitalized for ≥3 days with an acute medical illness, were enrolled in this observational cohort from 49 hospitals in 12 countries. Up to 31 March 2005, 6946 patients were enrolled. Results Based on autopsy series of all-cause in-hospital deaths reported in the literature, PE is associated with 10% of deaths, is the primary cause in 5%, and is clinically recognized as the primary cause in 1.5% of deaths. A review of clinical studies with mandatory venography resulted in predicted rates of 10% for all VTE and 1% for clinically recognized (confirmed) VTE. In IMPROVE, there were 4/291 (1.4%) deaths due to clinically recognized PE (vs. 4 predicted). There were 79 (1.1%) treated VTE events (vs. 69 predicted). Conclusions Observed rates of death due to PE and clinically recognized VTE in a real-world setting are consistent with predictions from clinical study data. Physicians should be aware of the significant gap that exists between clinically important and clinically evident VTE events. Reliance on the low rates of clinically recognized events to assess the seriousness of this disease can lead to a significant under-estimation of its impact on public health and a consequent failure to realize the proven benefits of VTE prophylaxis in hospitalized acutely ill medical patients.

Description: Abstract 2310 on behalf of the Steering Committee of the CALISTO Study. Background The CALISTO trial demonstrated the clinical benefit of anticoagulant therapy in patients with spontaneous isolated superficial-vein thrombosis (SVT) in the legs (n=3002).1 Compared with placebo, a 45-day once-daily subcutaneous treatment with fondaparinux 2.5 mg was associated with a 85% relative reduction in the risk of the composite of all-cause death and adjudicated symptomatic thromboembolic complications at day 47, a benefit that was maintained at 30-day follow-up (day 77) and was not associated with an increased bleeding risk. The benefit of fondaparinux was observed with the same magnitude on each thromboembolic component of the primary efficacy outcome, including symptomatic extension of SVT to the sapheno-femoral junction (SFJ). However, although all symptomatic extensions of the index SVT were reported and reviewed, only those within 3 cm of the SFJ were counted for the primary outcome. To better characterize the efficacy of fondaparinux we used a new composite efficacy outcome, including all symptomatic extensions of SVT, regardless of their distance from the SFJ. Methods The composite thromboembolic outcome of the original primary endpoint of the CALISTO trial included symptomatic pulmonary embolism (PE), symptomatic deep-vein thrombosis (DVT), symptomatic extension of the index SVT to ≤3 cm (EXT ≤3 cm) from the SFJ, and symptomatic recurrence of SVT (composite outcome CO-1). In a post-hoc analysis, we additionally included in the composite outcome (CO-2) all symptomatic extensions of the index SVT regardless of their final distance from the SFJ (EXT 〉3 cm). All symptomatic thromboembolic events were confirmed by appropriate objective tests and reviewed by an independent, central, blinded adjudication committee. Results Overall, symptomatic EXT ≤3 cm and EXT 〉3 cm of index SVT at day 77 were reported in 59 (2.0%) and 68 patients (2.3%), respectively. Compared with placebo, fondaparinux significantly reduced at day 77 both the rate of CO-1, from 6.2% (93/1500) to 1.1% (17/1502; RR, 0.18, 95% confidence interval [CI], 0.11 to 0.31, p3 cm from the SFJ, experienced symptomatic PE or DVT. Fondaparinux was associated with less use of medical resources, particularly in terms of surgery to treat SVT or need for anticoagulant therapy (Table). Conclusion Extension of the index SVT is a clinically relevant complication of the disease, regardless of the distance of the extension from the SFJ, and is associated with additional use of medical resources. Compared with placebo, fondaparinux reduced the rate of symptomatic thromboembolic complications in patients with spontaneous isolated SVT in the legs. 1 Decousus H, et al; CALISTO Study Group. N Engl J Med 2010;363:1222-32. Disclosures: Leizorovicz: BMS: Research Funding; Sanofi Aventis: Honoraria; Bayer: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria. Off Label Use: Fondaparinux for the treatment of Superficial Vein Thrombosis, labelled in Europe. Prandoni:GSK: Membership on an entity's Board of Directors or advisory committees. Décousus:GSK: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Boehringer Ingelheim: Research Funding; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees.

Description: Background Despite consensus group recommendations indicating that medical patients should receive appropriate venous thromboembolism (VTE) prophylaxis, prophylaxis practices remain poorly characterized. This analysis of IMPROVE, a prospective study of acutely ill medical patients, describes in-hospital prophylaxis practices prior to the publication of updated VTE prevention guidelines by the American College of Chest Physicians. Methods Patient recruitment began in July 2002. Patients ≥18 years old, and hospitalized for ≥3 days with an acute medical illness are enrolled consecutively. Exclusion criteria are: therapeutic antithrombotics/thrombolytics at admission; major surgery or trauma during 3 months prior to admission; and VTE treatment begun within 24 hours of admission. Results Data were from 4315 patients (32% from USA) enrolled up to 30 June 2004 in 37 hospitals in 11 countries (76% with 3-month follow-up data). Patients are 50% female, median (IQR) age 69 (50–80) years, median length of hospital stay 8 (5–14) days, median weight 68 (58–80) kg, and 40% were immobile for ≥3 days (median length of immobility 7 [4–14] days, including immobility immediately prior to admission). In-hospital VTE prophylaxis was received by 41% of patients (Table 1). Of patients with no risk factors (44%), one risk factor (40%), or ≥2 risk factors (16%), 25%, 49%, and 67% received prophylaxis, respectively. 12% of IMPROVE patients would have been eligible for inclusion in the MEDENOX study. Of these, only 52% received prophylaxis in hospital. Prophylaxis was provided to 6% of patients during the 3-month follow-up period, and continued in 11% of patients after discharge. Conclusions Only 41% of IMPROVE patients received VTE prophylaxis, with considerable variation in types and regimens of prophylaxis used. While MEDENOX showed the benefits of VTE prophylaxis (enoxaparin 40 mg) in acutely ill medical patients, only half of MEDENOX-eligible patients received prophylaxis. Table 1. Use of in-hospital VTE prophylaxis (N=4315) VTE prophylaxis Patients receiving VTE prophylaxis, % ROW, rest of world; *Excluding elastic stockings and aspirin ≥1 type of VTE prophylaxis* 41 LMWH - USA (Q12h, Qd) 7 (5, 1) LMWH- ROW (Q12h, Qd) 31 (29, 2) UFH - USA (Q12h, Q8h) 28 (15, 11) UFH - ROW (Q12h, Q8h) 6 (5, 0) Intermittent pneumatic compression (USA, ROW) 6 (19, 0) Aspirin (USA, ROW) 4 (7, 3) Elastic stockings (USA, ROW) 6 (3, 8)