Bemiparin versus Enoxaparin in the Prevention of Venous Thromboembolism among Intensive Care Unit Patients.
ABSTRACT: BACKGROUND:Critically ill patients are considered a high-risk group for developing venous thromboembolism (VTE). Due to their impaired cardiopulmonary reserve, these VTEs may result in significant morbidity and mortality. In this study, we compared two types of low molecular weight heparin, enoxaparin, and bemiparin, as regards to their efficacy and safety in VTE prevention among Intensive Care Unit (ICU) patients. METHODS:This study was a prospective, randomized trial of 100 critically ill patients who are at high risk for developing VTE were included in this study and assigned to receive subcutaneous injections of either 3500 international units (IU) anti-factor Xa of bemiparin sodium or 40 mg of enoxaparin given once a day and patient were followed for 60 days after initiation of anticoagulant therapy for the development of documented deep venous thrombosis (DVT) using bilateral lower limb venous duplex, documented pulmonary embolism using computed tomography pulmonary angiography, and complications related to injectant anticoagulant. RESULTS:Confirmed DVT was observed in two patients (4%) in the bemiparin group compared with 10 patients (20%) in the enoxaparin group with P < 0.05. Confirmed pulmonary embolism (PE) was observed in seven patients (14%) in the enoxaparin group with no recorded cases of confirmed PE in the bemiparin group (P < 0.05). No deaths were recorded in either group. Adverse events such as ecchymosis or hematoma at the injection site were observed in one patient (2%) in the bemiparin group and eight patients (16%) in the enoxaparin group (P < 0.05). There was no significant statistical difference between both groups as regards other adverse effects and complications related to the injectant anticoagulant. CONCLUSION:Bemiparin was superior to enoxaparin as a prophylactic anticoagulant for VTE in critically ill patients with less adverse local complications at the injection site. The study was registered on www.clinicaltrials.gov. Registration ID: NCT02795065. Registered June 8, 2016.
Project description:We compared the efficacy and safety of low-molecular-weight heparins (LMWHs) in patients with cancer who are at low risk of venous thromboembolism (VTE). Patients were treated by medical oncologists in Turkey at 15 sites, where they were enrolled and followed up for a period of 12 months. Due to the study design, there was no specific treatment protocol for LMWH. Primary end points were efficacy and the time to change in VTE status. Of the included 250 patients, 239 (95.6%), 176 (70.4%), 130 (52.0%), and 91 (36.4%) completed their day 15, month 3, month 6, and month 12 visits, respectively. Number of patients treated with enoxaparin, bemiparin, and tinzaparin were 133, 112, and 5, respectively. Anticoagulant therapy provoked thrombus resolution in 1.2% and 12.7% of patients using enoxaparin and bemiparin, respectively ( P = .004). Thrombus resolution was observed in 81 more patients at month 3 visit. This ratio was 35 (40.2%) of 87 and 46 (54.1%) of 85 patients administered enoxaparin and bemiparin at the third visit, respectively ( P = .038). Thrombus resolution was observed in 21 more patients during month 6 visit. This ratio was 5 (7.7%) of 65 and 15 (23.4%) of 64 patients administered enoxaparin and bemiparin at the fourth visit, respectively ( P = .022). The LMWH was discontinued in only 2 patients due to gastrointestinal bleeding. This pioneering study shows bemiparin is more effective than enoxaparin in thrombosis resolution and has a similar tolerability profile.
Project description:Venous thromboembolism (VTE) is a leading cause of maternal mortality and morbidity, with the highest incidence occurring during the postpartum period. This study compared the ability of two types of low-molecular-weight heparin, enoxaparin and bemiparin, to decrease the incidence of VTE following elective caesarean section, emergency caesarean section, and vaginal delivery in women who had risk factors for thromboembolism.In this prospective clinical trial using a sequential group allocation method, 7020 haemodynamically stable women delivered vaginally or abdominally at the Maternity Teaching Hospital, Kurdistan region, Erbil, Iraq, between May 1, 2012, and November 1, 2013. These women had risk factors for VTE and were allocated to the following groups: treatment with 3500 IU/day of bemiparin, 4000 IU/day of enoxaparin, or no intervention (control). The first dose was administered 6 hours after vaginal or abdominal delivery, or 8 hours after delivery in women receiving spinal anaesthesia. Subsequent doses were administered daily for up to 6 days. The incidence of VTE was assessed for up to 40 days postpartum. Data were analyzed using the Statistical Package for Social Sciences version 19. Proportions were compared using the chi square test of association or Fisher's exact test. Binary logistic regression analysis was used with VTE as the dependent variable.VTE occurred in 1 (0.042%) woman in the bemiparin group, two (0.085%) women in the enoxaparin group, and nine (0.384%) women in the control group (P?=?0.017). Regression analysis showed that women on bemiparin (OR?=?0.106; 95% CI?=?0.013-0.838) and enoxaparin (OR?=?0.226; 95% CI?=?0.049-1.049) were at lower risk of developing VTE than control women. Adverse events in the enoxaparin group included wound dehiscence, haematoma, and separation. None of these occurred in the bemiparin group.Postpartum bemiparin is significantly effective as a prophylaxis for VTE. Wound complications develop after use of enoxaparin, but not after bemiparin.ClinicalTrials.gov; Identifier: NCT01588171 ; date: April 26, 2012.
Project description:Background:The rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and coronavirus disease 2019 (COVID-19), has caused more than 3.9 million cases worldwide. Currently, there is great interest to assess venous thrombosis prevalence, diagnosis, prevention, and management in patients with COVID-19. Objectives:To determine the prevalence of venous thromboembolism (VTE) in critically ill patients with COVID-19, using lower limbs venous ultrasonography screening. Methods:Beginning March 8, we enrolled 25 patients who were admitted to the intensive care unit (ICU) with confirmed SARS-CoV-2 infections. The presence of lower extremity deep vein thrombosis (DVT) was systematically assessed by ultrasonography between day 5 and 10 after admission. The data reported here are those available up to May 9, 2020. Results:The mean (± standard deviation) age of the patients was 68 ± 11 years, and 64% were men. No patients had a history of VTE. During the ICU stay, 8 patients (32%) had a VTE; 6 (24%) a proximal DVT, and 5 (20%) a pulmonary embolism. The rate of symptomatic VTE was 24%, while 8% of patients had screen-detected DVT. Only those patients with a documented VTE received a therapeutic anticoagulant regimen. As of May 9, 2020, 5 patients had died (20%), 2 remained in the ICU (8%), and 18 were discharged (72%). Conclusions:In critically ill patients with SARS-CoV-2 infections, DVT screening at days 5-10 of admission yielded a 32% prevalence of VTE. Seventy-five percent of events occurred before screening. Earlier screening might be effective in optimizing care in ICU patients with COVID-19.
Project description:BACKGROUND: Clinical trials have shown low-molecular weight heparin (LMWH) to be at least as safe and efficacious as unfractionated heparin (UFH) for preventing venous thromboembolism (VTE) in acutely-ill medical inpatients. OBJECTIVE: To compare clinical and economic outcomes among acutely-ill medical inpatients receiving the LMWH enoxaparin versus UFH prophylaxis in clinical practice. METHODS: Using a large, multi-hospital, US database, we identified persons aged > or =40 years hospitalized for > or =6 days for an acute medical condition (including circulatory disorders, respiratory disorders, infectious diseases, or neoplasms) from Q4 1999 to Q1 2002. From these patients, those who received thromboprophylaxis with either enoxaparin or UFH were identified. Surgical patients and those requiring or ineligible for anticoagulation were excluded. We compared the incidence of deep-vein thrombosis (DVT), pulmonary embolism (PE), and all VTE (i.e., DVT and/or PE). Secondary outcomes were occurrence of side-effects, length of hospital stay and total costs. RESULTS: 479 patients received enoxaparin prophylaxis and 2,837 received UFH. The incidence of VTE was 1.7% with enoxaparin prophylaxis versus 6.3% with UFH (RR = 0.26; p < 0.001). Occurrence of side effects, length of stay (10.00 days with enoxaparin vs. 10.26 days with UFH; p = 0.348) and total costs ($18,777 vs. $17,602; p = 0.463) were similar in the 2 groups. CONCLUSION: We observed a 74% lower risk of VTE among patients receiving enoxaparin prophylaxis versus UFH prophylaxis. There was no significant difference in side effects or economic outcomes. These results provide evidence that the LMWH enoxaparin is more effective than UFH in reducing the risk of VTE in current clinical practice.
Project description:Optimal prophylaxis for prevention of venous thromboembolism (VTE) after total joint arthroplasty (TJA) remains debated. The purpose of this study was to compare postoperative complications in patients receiving different VTE chemoprophylactic regimens. Using a nationwide healthcare database, 72,670 THA patients without a history of VTE were identified. Study cohorts received VTE prophylaxis within 30 days postoperatively. Odds ratios and 95% confidence intervals were used to assess 30-day and 90-day postoperative complications (hematoma, hemorrhage, transfusion, pulmonary embolism (PE), VTE, prosthetic joint infection (PJI), and incision/drainage (I&D)). Of the 72,670 THA patients, 25,966 received single medication VTE prophylaxis; 551 (2.12%) aspirin, 6791 (26.15%) enoxaparin, 12,008 (46.25%) warfarin, 5403 (20.81%) rivaroxaban, 876 (3.37%) fondaparinux and 337 (1.30%) apixaban. 30-day complications included; aspirin: I&D; warfarin: I&D, hematoma, hemorrhage, transfusion, PJI, PE and DVT; apixaban: hematoma and hemorrhage. 90-day complications included; aspirin: I&D; warfarin: I&D, hematoma, hemorrhage, transfusion, PJI, PE and DVT. Warfarin was the only anticoagulant associated with a higher risk for DVT, and the highest risk for 30-day and 90-day complications. Aspirin had the highest risk for I&D. Despite three times increased 30-day risk for bleeding, apixaban was effective in preventing VTE during the high-risk 3-month-period. Enoxaparin had the lowest risk for PE and DVT while rivaroxaban had the lowest risk for PJI, hematoma, I&D, hemorrhage and transfusion.
Project description:<h4>Background</h4>After arthroplasty treatment, some complications commonly occur, such as early revision, infection/dislocation, and venous thromboembolism (VTE). This study aims to use a network meta-analysis to compare effects of 9 anticoagulant drugs (edoxaban, dabigatan, apixaban, rivaroxaban, warfarin, heparin, bemiparin, ximelagatran, and enoxaparin) in preventing postoperative complications in arthroplasty patients.<h4>Methods</h4>After retrieving PubMed, Embase, and Cochrane Library database from the inception to November 2016, randomized controlled trials were enrolled. The integration of direct and indirect evidences was performed to calculate odd ratios and the surface under the cumulative ranking curves. Nineteen eligible randomized controlled trials were included.<h4>Results</h4>The network meta-analysis results showed that compared with warfarin, edoxaban, apixaban, and rivaroxaban had a lower incidence rate in asymptomatic deep venous thrombosis, which indicated that edoxaban, apixaban, and rivaroxaban had better effects on prevention. Similarly, in comparison to enoxaparin, edoxaban and rivaroxaban had better effect; rivaroxaban was better than ximelagatran in preventive effects. Compared with apixaban, edoxaban, dabigatan, rivaroxaban, and enoxaparin had a higher incidence rate in clinically relevant non-major bleeding, which showed that preventive effects were relatively poor. In addition, the results of the surface under the cumulative ranking curves showed that rivaroxaban and bemiparin worked best on symptomatic deep venous thrombosis and pulmonary embolism. In terms of bleeding, apixaban and warfarin had better preventive effects.<h4>Conclusion</h4>Our findings suggested that rivaroxaban may work better in terms of symptomatic deep venous thrombosis and pulmonary embolism, whereas apixaban had better preventive effects in bleeding.
Project description:Background ?Elevated D-dimer concentrations are associated with an increased risk of venous thromboembolism (VTE). However, they may also provide prognostic value. The present analysis sought to study the association of D-dimer levels with VTE event rates and the efficacy of betrixaban versus enoxaparin in the APEX trial. Methods ?Hospitalized acutely medically ill subjects ( n ?=?7,513) were randomized in a double-dummy double-blind fashion to either extended-duration oral betrixaban (80?mg once daily for 35-42 days) or standard dose subcutaneous enoxaparin (40?mg once daily for 10?±?4 days) for venous thromboprophylaxis. D-dimer was assessed using a central core laboratory measurement. Results ?For every 0.25 µg/mL increase in D-dimer concentration, there was a 2% increase in the relative risk of experiencing the primary efficacy endpoint (asymptomatic deep vein thrombosis [DVT], symptomatic DVT, nonfatal pulmonary embolism, or VTE-related death) in both the betrixaban ( p ?<?0.001) and enoxaparin ( p ?<?0.001) treatment arms. Among D-dimer-positive (? 2?×?upper limit of normal; corresponding to ? 1.00 µg/mL) subjects, extended-duration betrixaban reduced the risk of experiencing the primary efficacy outcome (5.4% [ n ?=?124] vs. 7.6% [ n ?=?170]; odds ratio?=?0.69; 95% confidence interval: 0.55-0.88; absolute risk reduction?=?2.2%, number needed to treat?=?46, p ?=?0.003). There was no interaction between D-dimer and the treatment effect ( p int ?=?0.53). Conclusion ?Extended-duration betrixaban was superior to standard-duration enoxaparin, irrespective of D-dimer level at baseline. To prevent one VTE event, 46 D-dimer-positive patients would need to be treated with betrixaban.
Project description:Background Asymptomatic proximal deep vein thrombosis (DVT) is an end point frequently used to evaluate the efficacy of anticoagulant thromboprophylaxis in medical patients. Recently, the clinical relevance of asymptomatic DVT has been challenged. Methods and Results The objective of this study was to evaluate the relationship between asymptomatic proximal DVT and all-cause mortality (ACM) using a cohort analysis of a randomized trial for the prevention of venous thromboembolism (VTE) in acutely ill medical patients. Patients who received at least 1 dose of study drug and had an adequate compression ultrasound examination of the legs on either day 10 or day 35 were categorized into 1 of 3 cohorts: no VTE, asymptomatic proximal DVT, or symptomatic DVT. Cox proportional hazards model, with adjustment for significant independent predictors of mortality, were used to compare the incidences of ACM. Of the 7036 patients, 6776 had no VTE, 236 had asymptomatic DVT, and 24 had symptomatic VTE. The incidence of ACM was 4.8% in patients without VTE. Both asymptomatic proximal DVT (mortality, 11.4%; hazard ratio [HR], 2.31; 95% CI, 1.52-3.51; <i>P</i><0.0001) and symptomatic VTE (mortality, 29.2%; HR, 9.42; 95% CI, 4.18-21.20; <i>P</i><0.0001) were independently associated with significant increases in ACM. The analysis was post hoc, and ultrasound results were not available for all patients. Adjustment for baseline variables significantly associated with ACM may not fully compensate for differences. Conclusions Asymptomatic proximal DVT is associated with higher ACM than no VTE and remains a relevant end point to evaluate the efficacy of anticoagulant thromboprophylaxis in medical patients. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00571649.
Project description:<h4>Background</h4>Venous thromboembolism (VTE) is one of the most common preventable causes of in-hospital death in trauma patients surviving their injuries. We assessed the prevalence, incidence and risk factors for deep venous thrombosis (DVT) and pulmonary embolism (PE) in critically ill trauma patients, in the setting of a mature and early mechanical and pharmacological thromboprophylaxis protocol.<h4>Methods</h4>This was a prospective observational study on a cohort of patients from a surgical intensive care unit of a university level 1 trauma centre. We enrolled consecutive primary trauma patients expected to be in intensive care for ?48 h. Thromboprophylaxis was protocol driven. DVT screening was performed by duplex ultrasound of upper and lower extremities within the first 48 h, between 5 and 7 days and then weekly until discharge. We recorded VTE risk factors at baseline and on each examination day. Independent risk factors were analysed using a multivariate logistic regression.<h4>Results</h4>In 153 patients with a mean Injury Severity Score of 23 ± 12, the prevalence of VTE was 30.7%, 95 CI [23.7-38.8] (29.4% DVT and 4.6% PE). The incidence was 18%, 95 CI [14-24] patients-week. The median time of apparition of DVT was 6 days [1; 4]. The global protocol compliance was 77.8% with a median time of introduction of the pharmacological prophylaxis of 1 day [1; 2]. We identified four independent risk factors for VTE: central venous catheter (OR 4.39, 95 CI [1.1-29]), medullar injury (OR 5.59, 95 CI [1.7-12.9]), initial systolic arterial pressure <80 mmHg (OR 3.64, 95 CI [1.3-10.8]), and pelvic fracture (OR 3.04, 95 CI [1.2-7.9]).<h4>Conclusion</h4>Despite a rigorous, protocol-driven thromboprophylaxis, critically ill trauma patients showed a high incidence of VTE. Further research is needed to tailor pharmacological prophylaxis and balance the risks and benefits.
Project description:BACKGROUND:Statins may reduce the risk of first and recurrent venous thromboembolism (VTE). No data are available on their potential benefit in patients treated with the oral anticoagulant rivaroxaban. METHODS:The EINSTEIN DVT/PE and EINSTEIN Extension studies compared rivaroxaban with standard of care (n=8280) and placebo (n=1188), respectively. The incidences of recurrent VTE and major bleeding per 100 patient-years for exposure (or not) to statins were calculated. A Cox proportional hazards model was constructed, stratified by index event and intended treatment duration, with statin use as a time-dependent variable, for each treatment group (rivaroxaban vs enoxaparin/vitamin K antagonist or placebo) and adjusted for relevant variables. RESULTS:In EINSTEIN DVT/PE, 1509 (18.3%) patients used statins during the at-risk period, and 6731 (81.7%) did not. Overall, 2.6 recurrent VTEs occurred per 100 patient-years with statin use compared with 3.8 per 100 patient-years without statins (adjusted hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.46-1.25). HRs for recurrent VTE were similar for concomitant use of rivaroxaban-statin and enoxaparin/VKA-statin. Major bleeding events occurred in 3.0 per 100 patient-years with statin use compared with 2.3 per 100 patient-years without statins (adjusted HR 0.77; 95% CI 0.46-1.29). Due to adjustments in the Cox regression model, the direction of this HR is in contrast to the crude comparison. In EINSTEIN Extension, no recurrent VTEs occurred with statin use in the rivaroxaban group compared with 1.6 per 100 patient-years without statins. In the placebo group, 12.2 recurrent VTEs occurred per 100 patient-years with statin use compared with 13.2 per 100 patient-years without (adjusted HR 0.81; 95% CI 0.35-1.86). CONCLUSIONS:The effect of statins in this secondary analysis of the EINSTEIN VTE treatment program is consistent with other studies that suggest a reduced risk of recurrent VTE, but conclusive evidence of this benefit is lacking. Statins are simple to use, inexpensive, very safe and do not cause bleeding. Therefore, the potential effect on reducing recurrent VTE, which is in the range of that of acetylsalicylic acid, deserves evaluation in a large randomized trial. TRIAL REGISTRATION NUMBER:ClinicalTrials.gov: EINSTEIN PE, NCT00439777; EINSTEIN DVT, NCT00440193; EINSTEIN Extension, NCT00439725.