Reduction In Risk Of Venous Thromboembolism Research Articles

Dyslipidemia, Statins, and Venous Thromboembolism

Venous thromboembolism (VTE) is one of the most frequent and serious vascular diseases. Although the major risk factors of VTE are well recognized, the pathology often develops in subjects without any obvious precipitating factor. Recent evidence suggests a link between arterial and venous thrombosis, particularly in patients with idiopathic venous thrombosis. Therefore, similar or identical risk factors may play a role in the development of both diseases. A positive association between classical risk factors of atherosclerosis, including dyslipidemia, and VTE has been reported. Recent studies demonstrated an association between hypercholesterolemia and objectively verified VTE. Circulating lipids have been shown to have both prothrombotic- and endothelium-deteriorating properties. Studies suggested a greater generation of thrombin, endothelial dysfunction, and higher platelet activity in hyperlipidemic blood. By impeding these mechanisms, statins may protect against VTE. Observational, controlled studies and two meta-analyses showed that statins significantly reduced VTE risk, most likely in a process independent from cholesterol lowering, through mechanisms related to the pleiotropic effects of these drugs. Currently, it is unknown whether VTE prevention is a class-effect of statins, or if statins differ in their antithrombotic efficacy, and it is also unknown if statin benefit is dose-dependent. However, there are also opposite findings about the efficacy of statins in prevention of VTE. Therefore, the use of statins for prophylaxis of VTE cannot be generally recommended at this stage. Further studies are needed to identify those patients who could eventually benefit maximally from treatment with statins for prevention of VTE.

Thromboembolism and Antithrombotic Therapy in Patients With Heart Failure in Sinus Rhythm

Heart failure (HF) represents a major and growing public health problem because of its prevalence, incidence, morbidity, mortality, and economic costs. The prevalence of HF is 2% to 3% of the general population.1 Five million Americans are affected, with >550 000 cases diagnosed each year.2 The mortality rate from severe HF remains >60% within 5 years of diagnosis, and 50% of hospitalized patients with HF require readmission within 6 months of discharge. In the US estimated costs amount to > $35 billion per year.3 Although several therapies (eg, β-blockers, angiotensin-converting enzyme [ACE] inhibitors, and cardiac resynchronization therapy) have been proven effective in improving HF outcomes, many unanswered questions about optimal treatment remain. One area of ongoing uncertainty is the appropriate role for antithrombotic therapy in patients with HF. Observational data suggest that patients with HF have an increased venous thromboembolism (VTE) risk (deep venous thromboembolism [DVT], pulmonary embolism [PE], peripheral arterial thromboembolism, and stroke).4 These epidemiological findings are supported by multiple mechanisms that can contribute to a hypercoagulable state in patients with HF. Despite this increased risk of VTE, the role of antithrombotic therapy remains unclear. In this article, we provide an overview of epidemiology, pathophysiology, clinical trial data, and therapeutic recommendations for prevention of thromboembolism in HF. We searched PubMed for articles published between 1958 and 2010 using the following search terms: epidemiology of heart failure , thromboembolism and heart failure , thrombogenesis and heart failure , anticoagulation in heart failure , antiplatelet agent and heart failure , aspirin and heart failure , bleeding risk and anticoagulation , and aspirin and angiotensin-converting enzyme inhibitors . We also studied abstracts from national and international cardiovascular meetings to identify unpublished studies using the key words anticoagulation and dilated cardiomyopathy . Data from published observational studies and secondary …

Rates of venous thromboembolism in multiple myeloma patients undergoing immunomodulatory therapy with thalidomide or lenalidomide: a systematic review and meta‐analysis

The incidence of venous thromboembolism (VTE) in patients with multiple myeloma (MM) treated with thalidomide- and lenalidomide-based regimens is high. Recent observational studies have suggested that thromboprophylaxis might be efficacious in decreasing the risk of VTE in this population. To determine the absolute rates of VTE with and without different thromboprophylactic agents in patients with newly diagnosed or previously treated MM receiving thalidomide- or lenalidomide-based regimens. Patients with newly diagnosed MM treated with thalidomide in combination with dexamethasone have a VTE risk of 4.1 (95% CI, 2.8-5.9) per 100 patient-cycles. Therapeutic doses of anticoagulants seem to provide the largest absolute risk reduction of VTE. The rate of VTE in patients with previously treated MM receiving thalidomide in combination with dexamethasone is 0.8 (95% CI, 0.1-2.1) per 100 patient-months. A combination of lenalidomide and dexamethasone is associated with of risk of VTE of 0.8 (95% CI, 0.07-2.0) per 100 patient-cycles and 0.7 (95% CI, 0.4-0.9) per 100 patient-cycles in patients with newly diagnosed and previously treated MM, respectively. Similarly, the rates of VTE in patients also receiving thromboprophylaxis with aspirin were 0.9 (95% CI, 0.5-1.5) and 0.6 (95% CI, 0.01-2.1), respectively. Patients with newly diagnosed or previously treated MM receiving thalidomide- or lenalidomide-based regimens in combination with dexamethasone are at high risk of VTE. The benefit of various types of thromboprophylaxis is difficult to quantify in patients with MM receiving immunomodulatory therapy, especially in those receiving lenalidomide-based therapy or who have previously treated MM. Randomized controlled trials are needed to address this important clinical need.

Prevention of venous thromboembolism in obesity

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in hospitalized patients. Where appropriate, evidence-based methods of prophylaxis are implemented and the burden of VTE can be reduced substantially. Obesity, including morbid obesity, is associated with a high risk of VTE and, unfortunately, fixed doses of US FDA-approved anticoagulant regimens, including unfractionated heparins, low-molecular-weight heparins and factor Xa inhibitors, may not provide optimal VTE prophylaxis in these patients. Although the data are still limited, a rapidly growing body of literature and cumulative evidence suggests that anticoagulant dose adjustments in morbidly obese patients may optimize pharmacodynamic activity and reduce VTE risk. With the prevalence of morbid obesity continuing to rise, more high-quality clinical data are needed to better understand the pathobiology of VTE in obesity and provide effective, yet safe, prevention strategies.

Statin Therapy and Levels of Thrombosis Risk Factors In a Healthy Population: the Multi-Ethnic Study of Atherosclerosis

AbstractAbstract 3178 Background:HMG CoA reductase inhibitors (statins) were recently reported to reduce the rate of venous thromboembolism (VTE) in healthy people. Statins reduce levels of inflammation biomarkers, however the mechanism for a reduction in VTE risk is unknown. We studied cross-sectional associations of statin use with hemostatic factors related to venous thrombosis risk in a large cohort of healthy people. Methods:Cross-sectional analyses were performed in the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort study of 6814 healthy men and women age 45–84, free of clinical cardiovascular disease at baseline; 1001 were using statins. Twenty three warfarin users were excluded. Age, race, and sex-adjusted mean hemostatic factor levels were compared between statin users and nonusers, and multivariable linear regression models were used to assess associations of statin use with hemostasis factors, adjusted for age, race/ethnicity, education, income, hormone replacement therapy (in women) and major cardiovascular risk factors. Results:The table shows that those using statins had significantly lower levels of D-dimer, C-reactive protein and factor VIII than non-users. Homocysteine and von Willebrand factor did not differ by statin use. Specific adjustment for LDL and triglycerides did not attenuate the observed differences in these factors by statin use. Conclusions:Findings of lower D-dimer, factor VIII and C-reactive protein levels with statin use suggest mechanisms whereby statins might lower VTE risk. These associations were not explained by lipid levels on treatment. A prospective study linking these biochemical differences to VTE outcomes is warranted. Disclosures:No relevant conflicts of interest to declare.

Prevalence of Venous Thromboembolism In Patients with Secondary Polycythemia

AbstractAbstract 3164 Background:Polycythemia vera is associated with an increased risk for venous thromboembolism (VTE). Although phlebotomy is employed as an adjunct to treatment with hydroxyurea and/or aspirin for VTE risk reduction, emerging data suggest that hematocrit is less of a determinant of VTE risk than leukocyte count and JAK2 V617F gene mutation allele burden. The role of secondary polycythemia as a risk factor for VTE is unknown, but phlebotomy for thrombosis risk reduction is frequently practiced. Based on the polycythemia vera model, however, we hypothesize that secondary polycythemia does not increase VTE risk. The purpose of this study was to determine the prevalence of VTE in patients with secondary polycythemia and to investigate the factors associated with VTE in this population. Methods:We performed a case control study that included patients admitted to Dartmouth-Hitchcock Medical Center with a diagnosis of chronic obstructive pulmonary disease (COPD) and a hematocrit greater than or equal to 50% from August 2004 to July 2009. The controls were matched for age and sex and carried a diagnosis of chronic obstructive pulmonary disease (COPD) without evidence of secondary polycythemia. Data were collected on body mass index (BMI), VTE history, comorbid conditions, thrombophilia and smoking history. Clinical characteristics of patients with and without secondary polycythemia were analyzed using chi square and t-test to evaluate for significant differences in the two populations. Results:Eighty-six patients with secondary polycythemia and 86 controls were included in the study. The mean hematocrit was 53.5% in the case group and 43.7% in the control group (p=<0.005). Among cases, a history of VTE was documented in 17/86 (19.8%), 10 of which (58.8%) were judged to be idiopathic. In the control group, VTE was documented in 12/86 (14%), 4 of which (33.3%) were judged to be idiopathic. There was no statistically significant difference in the number of total (OR=1.52, p=0.42) or idiopathic (OR=2.7; p=0.16) VTE between cases and controls, respectively. There were no statistically significant differences noted in age, sex, body mass index, presence of diabetes mellitus, smoking history or the presence of malignancy in the two groups. Patients with VTE in both groups had higher BMI, however, compared to patients without VTE. Conclusions:We did not observe an increased prevalence of VTE in patients with secondary polycythemia compared to age- and sex-matched controls. Our findings suggest that the high prevalence of VTE observed in patients with secondary polycythemia is more likely related to known risk factors such as obesity rather than hyperviscosity due to increased cell mass. The role of phlebotomy for VTE risk reduction in patients with secondary polycythemia is therefore questionable. Disclosures:No relevant conflicts of interest to declare.

Risk Factors for Venous Thromboembolism In Hospitalized Cancer Patients with Central Catheters

AbstractAbstract 810 Background:The incidence of venous thromboembolism (VTE) and central venous catheter (CVC) related thrombosis is increased in cancer patients, in particular those with advanced hematologic malignancies. Bloodstream infection (BSI) is thought to increase CVC associated thrombosis in several small studies. In July 2007, systematic changes including intensive education, process changes and use of the Biopatch.. (Ethicon 360) were effective in decreasing the incidence of BSI (from 3% to 0.7%) at the Hospital of the University of Pennsylvania (HUP).Our primary objective was to identify risk factors for VTE in hospitalized cancer patients, particularly hematologic malignancy and stem cell transplant (SCT) patients. Secondary objectives were to evaluate the effect of VTE prophylaxis and infection control measures in preventing VTE and CVC thromboses and describe treatment strategies in this population. Methods:After IRB approval was obtained, patients admitted to oncology floors were identified using an inpatient database. This was cross-referenced with an Interventional Radiology Hickman catheter placement database. Demographic and clinical data were retrieved retrospectively from the electronic medical record (EMR). Clinical events including objectively documented VTE were confirmed by review of the EMR by investigators. A case-control study was performed. Odds ratios were calculated for risk factors associated with thrombosis and univariate and multivariate regression analysis was performed. Results:Between July 1, 2005 and June 30, 2009, 770 oncology inpatients had a tunneled catheter placed. 50 patients with a VTE after the CVC was placed were identified as cases. 182 controls without VTE were identified randomly. Mean patient age with and without VTE was 52 and 53 years respectively. Women constituted 42% and 41% of patients with and without VTE. Diagnoses in cases include leukemia in 33 (66%), lymphoma in 7 (14%), myeloma in 4 (8%), MDS and aplastic anemia in 1 each (4%) and solid tumor in 4 (8%). Types of SCT in cases were allogeneic in 16 (62%), non-myeloablative in 4 (15%) and autologous in 6 (23%).Of the 50 cases, 15 (31%) had multiple VTEs, 26 (52%) were CVC associated, 17 (34%) were DVT and 4 (8%) were PE. No VTE prophylaxis was used in 22 (47%) of cases. Median platelet count at time of thrombosis was 86. Anticoagulant therapy was used in 33 patients (67%), including UFH in 28 (85%) and LMWH in 5 (15%). Bleeding during anticoagulation occurred in 4 cases (12%). With regard specifically to CVC thrombosis, 13 (50%) cases presented before infection control measures were put in place, and 13 (50%) after, vs. controls (38% before and 62% after) (p= 0.23). BSI was present in 16 (62%) cases and 51 (28%) of controls (p = 0.27). In a SCT subset analysis, VTE occurred in 26 (31%) of 83 SCT patients vs. 25 (17%) of 150 nonSCT patients (p=0.01); CVC thrombosis occurred in 14 (20%) SCT patients vs. 12 (9%) nonSCT patients (p=0.02).Risk factors for venous thrombosis by univariate analysis include:VariableOR95% CIp-valueRelapsed/refractory Heme Malignancy2.151.11–4.230.01History of VTE3.011.00–8.990.02History of Obesity6.251.84–24.070.003Post SCT10.203.52–29.55<0.001VTE prophylaxis0.530.28–0.990.03Left sided CVC2.331.03–5.140.02BSI1.550.82–2.910.14Biopatch ..1.540.83–2.780.14Active chemo0.420.20–0.880.01In multivariate regression analysis, the following risk factors remained statistically significant: status post SCT (p = 0.001); obesity (p = 0.02); line type- PICC (p = 0.02); CVC not in the internal jugular (IJ) vein (p=0.03), and CVC tip not in the superior vena cava (SVC) (p=0.003). Conclusions:Subjects with a history of VTE, obesity, advanced hematologic malignancies and SCT recipients were more likely to develop a VTE. Active chemotherapy did not increase the risk of VTE. CVC related risk factors include left sided placement, non- IJ vessel, and tip not in the SVC. While the presence of BSI was minimally associated with CVC- thrombosis, use of infection control measures did not significantly reduce VTE risk. VTE prophylaxis appears to be effective in preventing VTE; however 47% of cases were not on any, suggesting that at least mechanical measures may be warranted in high risk patients. Thrombocytopenia is not protective against VTE and should not preclude prophylaxis in these patients. Additional studies are warranted to further define risk factors for VTE in this population. Disclosures:Trerotola:Bard: Consultancy; MedComp: Consultancy; Cook: Consultancy; Teleflex: Consultancy; Grant Adler: Consultancy.

Venous Thromboembolism Prophylaxis among Elderly Heart Failure Patients and 60-Day Outcomes: An Analysis from ADHERE Linked to Medicare Claims

Background: Hospitalized medically ill patients are at increased risk for venous thromboembolism (VTE). While antithrombotic prophylaxis regimens have reduced VTE risk in medically ill patients, their effectiveness for post-discharge outcomes among HF patients is unknown. Methods: We used ADHERE registry data linked to Medicare claims. We included patients hospitalized from 2001 to 2004, discharged alive. Patients on warfarin or IV heparin were excluded. We estimated observed 60-day rates of mortality, thromboembolic events, major adverse cardiovascular events (MACE), and rehospitalization for HF using estimates based on the cumulative incidence function.

Risk factors for developing a new venous thromboembolism in ambulatory patients with non-hematologic malignancies and impact on survival for gastroesophageal malignancies.

Venous thromboembolism(VTE) is a significant, common comorbidity of cancer patients associated with increased mortality. We evaluated the incidence and risk factors for developing a new VTE in ambulatory cancer patients while they were receiving therapy for advanced cancer. We also examined the affect of developing a new VTE on survival for patients with gastroesophageal malignancies. All patients with non-hematologic malignancies who were treated using investigator-initiated therapeutic protocols at Memorial Sloan Kettering Cancer Center (MSKCC) from 2003 through to 2005 were identified for this cohort study. The occurrence of VTE was prospectively recorded in an actively managed clinical research database. Baseline laboratory parameters, treatment details and tumor type were correlated with VTE risk and patient survival. 115 out of 2120 patients being treated for advanced malignancy developed a new VTE (12.8 VTEs/100 person-years). In multivariate analysis, a diagnosis of gastroesophageal cancer (hazard ratio (HR), 2.76 (1.41-5.38); P=0.003), pancreatic cancer (HR, 2.26 (1.06-4.80); P=0.05), use of white cell growth factors (HR 1.69(1.09-2.64); P=0.02) and irinotecan therapy (HR, 1.89 (1.29-3.59); P=0.05) were independently associated with VTE development. Hemoglobin >10 g dL(-1) (HR, 0.52 (0.3-0.91); P=0.02) and albumin ≥ 4 g dL(-1) (HR, 0.61 (0.39-0.94); P=0.024) were associated with reduced VTE risk. The unadjusted HR for death among ambulatory gastroesophageal cancer patients with VTE is 0.89 (0.61-1.3), P=0.53. After adjusting for confounding risk factors associated with survival, the HR for death associated with VTE is 0.78 (0.5-1.2), P=0.25. Upper gastrointestinal malignancies are independently associated with the development of a new VTE, implicating tumor biology in VTE development. Even after adjusting for prognostic factors, we were unable to demonstrate an adverse impact on survival due to the new development of VTE amongst patients with active gastroesophageal malignancy receiving therapy.

NICE guidance on reducing the risk of venous thromboembolism in patients admitted to hospital

NICE guidance on reducing the risk of venous thromboembolism in patients admitted to hospital

Statins, fibrates, and venous thromboembolism: a meta-analysis

The aim is to make a systematic review of the literature to assess the effect of lipid-lowering drugs on venous thromboembolism (VTE) occurrence. MEDLINE and EMBASE databases were searched to identify studies that evaluated the effect of lipid-lowering drugs, in particular statins and fibrates, on VTE risk until April 2009. A scoring system was used to divide studies into two quality categories. Odds ratios (ORs) and 95% confidence intervals (CIs) were then calculated and pooled using a fixed and a random-effects model. Statistical heterogeneity was evaluated through the use of I(2) statistics. Three randomized controlled trials (RCTs), three cohort, and eight case-control studies were included in our systematic review, for a total of 863 805 patients. Statins use significantly reduced VTE risk [OR, 0.81; 95% CI, 0.66-0.99, random-effect model)]. There was a very high heterogeneity among the studies (I(2) > 80%). The use of fibrates was associated with a significant increase in the risk of VTE (OR, 1.58; 95% CI, 1.23-2.02), without heterogeneity (I(2) = 0%). Data on other lipid-lowering drugs were lacking. This meta-analysis of available literature suggests that statins may lower the risk of VTE, whereas fibrates may increase this risk. Due to several methodological limitations, this conclusion should be considered with caution, and additional, specifically designed RCTs are warranted.

Low Molecular Weight Heparin Thromboprophylaxis in Ambulatory Cancer Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Abstract 490 Background:Patients with cancer experience an increased risk of venous thromboembolism (VTE) throughout the course of their illness. The risk of VTE appears to be greatest among hospitalized cancer patients, in the perioperative period of major surgery and in those receiving systemic cancer therapies. While encouraged in hospitalized and surgical patients, routine VTE prophylaxis for cancer patients is not recommended in the ambulatory setting except in very selective high risk circumstances. A number of randomized clinical trials (RCTs) of low molecular weight heparin (LMWH) in ambulatory cancer patients have been reported with inconsistent results. Presented here are the results from our updated meta-analysis of LMWH prophylaxis, including recently presented RCTs. Methods:A systematic review of RCTs of VTE prophylaxis with LMWH in ambulatory cancer patients was conducted including the results of published and recently presented trials. Electronic databases including Medline, EMBASE, and Cochrane Library were searched along with meeting abstracts from ASCO and ASH. Eligibility criteria included RCTs of ambulatory cancer patients randomized to LMWH or not and reporting rates of VTE as a primary outcome (primary VTE prophylaxis studies) or a secondary outcome. Dual blinded data extraction was performed with conflict resolution by a third party. Following assessment of heterogeneity, meta-analyses using the method of Mantel and Haenszel were conducted providing weighted summary estimates of both relative risk (RR) and absolute risk (AR) ± 95% confidence intervals (95% CI). Primary study outcomes consist of all reported VTE events and all major bleeds. Most trials did not require VTE screening by imaging, precluding a separate analysis of asymptomatic VTE events. Results:A total of 7 RCTs of LMWH in ambulatory patients with cancer were identified with a total of 2,960 patients including 1,685 receiving LMWH and 1,275 controls. These include 3 RCTs with various solid tumors and one RCT each in breast cancer, lung cancer, pancreatic cancer, and glioblastoma. Patients receiving LMWH experienced 47 VTE events compared to 74 control subjects for crude rates of 2.79% and 5.80%, respectively. No significant heterogeneity was observed across trials (Cochran Q=6.19; I2=3.03; P=.40). The RR for VTE across trials was estimated at 0.54 [95% CI: 0.38 – 0.78; P=.001] while the AR decrease was 2.55% [95% CI: 1.06% – 4.05%; P<.001]. The RR for VTE for the 5 primary VTE prophylaxis trials was 0.50 [95% CI: 0.34 – 0.75; P<.001] with an AR decrease estimated at 2.95% [95% CI: 1.26 – 4.63%; P<.001]. Major bleeding events were reported in 30 patients receiving LMWH compared to 15 control subjects for crude rates of 1.78% and 1.18%, respectively. No significant heterogeneity was observed across trials (Cochran Q=5.50; I2=0.0; P=.481). The RR for major bleeding across trials was estimated at 1.74 [95% CI: 0.95 – 3.18; P=.071], while the AR increase was 0.75% [95% CI: 0.17% – 1.33%; P=.011]. The RR for major bleeding in the 5 primary prophylaxis trials was 2.27 [95% CI: 1.12 – 4.59; P=.022] with AR increase estimated at 1.27% [95% CI: 0.27% – 2.27%; P=.013]. Conclusions:LMWH thromboprophylaxis in ambulatory cancer patients is effective and results in a significant 46% relative risk reduction of venous thromboembolism. However, the risk of VTE is low in this setting and the absolute risk reduction with prophylactic anticoagulation is only 2.6%, while concerns remain about the increase in major bleeding events. Additional research is needed to identify ambulatory cancer patients at increased risk for VTE, in whom VTE prophylaxis may have a more favorable risk-benefit ratio. Disclosures:Ortel:Eisai: Research Funding. Khorana:sanofi-aventis: Consultancy; Eisai: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding. Francis:Eisai: Consultancy, Honoraria.

Low-molecular-weight heparin for venous thromboprophylaxis in ambulatory cancer patients: A meta-analysis

9537 Background: Patients with cancer have an increased risk of venous thromboembolism (VTE). However, routine VTE prophylaxis is generally not recommended in ambulatory cancer patients. Several randomized controlled trials (RCTs) of low-molecular-weight heparin (LMWH) in ambulatory cancer patients have been reported with inconclusive results. Methods: A systematic review of RCTs of LMWH in ambulatory cancer patients without a VTE diagnosis was conducted. Included trials had to report VTE as primary or secondary outcome. An extensive electronic database search was conducted, including Medline, EMBASE, Cochrane Library along with abstracts from major meetings. Dual-blinded data extraction was performed. Meta-analysis was conducted using Mantel and Haenszel method to estimate relative risk (RR) and absolute risk difference (ARD) ± 95% CI. Primary outcomes in this analysis were all reported VTE and major bleeds. Most trials did not require VTE screening by imaging, precluding a separate analysis of asymptomatic VTE events. Results: Six RCTs were identified with a total of 2,648 patients including 1,525 receiving LMWH and 1,123 controls. No significant heterogeneity was observed across trials. Among patients receiving LMWH, the crude incidence of VTE was 2.95% compared to 5.25% among control patients. LMWH reduced the RR of VTE by 36% compared to controls (RR=0.64 [0.44 - 0.94], P=0.021), and reduced the ARD by 1.8% [0.2% - 3.4%]. Major bleeding events were reported in 1.57% LMWH patients compared to 0.98% in controls. The non-significant RR increase by LMWH for major bleeding was 1.85 [0.923 - 3.68], P=0.081, with an ARD of 0.9% [0.0% - 1.8%]. Results were comparable in the analysis limited to studies with VTE as primary outcome. Conclusions: While patients experienced a 36% relative risk reduction in VTE with LMWH, the absolute risk reduction was small, and concerns remain about the potential increase in major bleeding. Therefore, routine VTE prophylaxis in ambulatory cancer patients cannot be recommended at this time. Additional research is needed to identify cancer outpatients at high risk for VTE, in whom prophylaxis may have a more favorable risk-benefit ratio. [Table: see text]

Flu Shot May Protect Against Vein Problems

NEW ORLEANS — Influenza vaccination reduced the incidence of venous thromboembolism by 26% in a case-control study. This novel finding requires confirmation. Should that happen, it would become appropriate to recommend a change in clinical practice incorporating routine administration of influenza vaccine by injection as a means of preventing repeat venous thromboembolism (VTE) episodes in all patients who have experienced pulmonary embolism or deep vein thrombosis, Joseph Emmerich, MD, PhD, said at the annual scientific sessions of the American Heart Association. He presented an 11-center retrospective case-control study involving 727 French adults with a first objectively documented episode of VTE and no history of cancer within the prior 5 years, and an equal number of VTE-free controls. Participants were asked if they had received a flu shot—the nasal spray flu vaccine isn't available in France—within the past 12 months. Among the participants, 28.2% of those with VTE and 32.1% of controls had received a flu shot. After adjustment in a multivariate regression analysis for potential confounders including age, sex, body mass index, use of oral contraceptives, education level, and varicose veins, influenza vaccination was associated with a highly significant 26% relative risk reduction in VTE. In participants younger than age 52 years—the median age of the study population—the relative risk reduction was even larger, at 48%. The preventive effect was of similar size against pulmonary embolism and deep vein thrombosis, according to Dr. Emmerich, professor of vascular medicine at the René Descartes University, Paris. The protective effect against VTE associated with flu vaccination was particularly robust in women. In women younger than 51 years, the unadjusted risk of VTE associated with flu vaccination was reduced by 50%. After adjustment for oral contraceptive use and other potential confounders, the relative risk reduction rose to 59%. Dr. Emmerich listed several potential mechanisms for influenza vaccination's apparent protective effect against VTE. One possibility is that by protecting individuals from getting the flu, vaccination prevents them from being immobilized in bed for days, a VTE risk factor. Another possibility is that infection with the influenza virus provokes a systemic inflammatory reaction that could promote thrombosis. Arguing against either of these proposed mechanisms, however, was the fact that VTE events were evenly distributed throughout the year, Dr. Emmerich noted. Dr. Emmerich is planning a definitive multicenter, randomized, prospective study of influenza vaccination for secondary prevention of VTE. His case-control study was funded by the French national medical research foundation and other academic sources. The American Heart Association recommends annual flu shots in patients with cardiovascular disease, as they are at increased risk of death when they do contract influenza. Bruce Jancin is with the Denver bureau of Elsevier Global Medical News.

Fibrinogen gamma gene 3’-end polymorphisms and risk of venous thromboembolism in the African-American and Caucasian population

Genetic determinants of venous thromboembolism (VTE) in the African-American population are poorly characterised. It was recently shown that fibrinogen gamma gene (FGG) polymorphisms 10034C>T and 9340T>C influence VTE risk in the Caucasian population. In the African-American population these polymorphisms are common, with allele frequencies above 25%. Here we evaluated whether these and other FGG 3'-end polymorphisms were associated with VTE risk in the African-American population and aimed to replicate the association in the Caucasian population. We examined 557 Caucasian patients and 678 Caucasian controls, and 537 African-American patients and 586 African-American controls from the ;Genetic Attributes and Thrombosis Epidemiology' (GATE) study. In the African-American population, 10034C>T and 9340T>C marginally influenced VTE-risk, with a 20% increase in risk for 10034TT carriers and a 20% reduction in risk for 9340CC carriers. In the Caucasian population, 10034TT was associated with a 1.7-fold increase in risk, which increased to 2.1-fold for idiopathic VTE patients. 9340CC significantly reduced VTE risk approximately two-fold. In conclusion, both FGG polymorphisms 10034C>T and 9340T>C influence VTE-risk, with the strongest effects observed in the Caucasian population, confirming previous data on these polymorphisms in this population.

PL-37: Prophylactic measures to reduce the risk of venous thromboembolism in bariatric surgery: Chemoprophylaxis added to sequential compression may not reduce this risk when compared to sequential compression alone

The use of sequential compression devices on lower extremities perioperatively and early ambulation reduce venous thromboembolism (VTE) postoperatively. Anti-coagulation medication is recommended by ASMBS to reduce VTE risk. This study examines 30 day post-op VTE or death among bariatric surgery patients who had sequential compression alone (SEQUEN) or with anticoagulation (ANTICOAG).

PL-38: Low surgical volumes in hospitals that meet surgical review corporation (SRC) bariatric surgery center of excellence (BSCOE) minimum standards do not demonstrate an adverse impact on surgical outcomes

extremities perioperatively and early ambulation reduce venous thromboembolism (VTE) postoperatively. Anti-coagulation medication is recommended by ASMBS to reduce VTE risk. This study examines 30 day post-op VTE or death among bariatric surgery patients who had sequential compression alone (SEQUEN) or with anticoagulation (ANTICOAG). Methods: LABS participants from 10 centers in the US who underwent their first bariatric surgery between 3/2005 and 10/2007 comprise the study group. We examined 30-day incidence of VTE, defined as DVT or PE, and mortality. Results: Of 3,539 patients, 370 (10%) received sequential compression alone, while the others also received anticoagulation therapy. The two groups were similar in age, race, ethnicity, and BMI. There was a significantly higher percentage of males (30% vs. 20%, p 0.0001) and smokers (7% vs. 3%, p 0.003) in the SEQUEN group. The prevalence of hypertension, diabetes, congestive heart failure, history of VTE , vena cava filter, ischemic heart disease, and pulmonary hypertension at baseline, were not significantly different. The SEQUEN group had longer operative times (207 vs. 169 min, p .0001). The two groups were similar in % of re-hospitalization and re-operation. Open surgery was associated with 1.8% of VTE, and laparoscopic surgery with 0.4%. After adjusting for sex, current smoking, length of operation, and history of VTE, there was not a significant difference between groups in the combined incidence of DVT/PE/mortality (1.0% in ANTICOAG versus 0.4% in SEQUEN, p 0.25). Conclusion: The overall incidence of VTE or death was small (1%). The addition of anticoagulation to the use of sequential compression devices may not lower the rate of VTE following bariatric surgery. Further study of this topic is warranted (sample size). PII: S1550-7289(08)00406-1

Prevention of venous thromboembolism in the orthopedic surgery patient.

Patients undergoing major orthopedic surgery--hip or knee arthroplasty, or hip fracture repair--are in the highest risk category for venous thromboembolism (VTE) solely on the basis of the orthopedic procedure itself. Despite this, nearly half of patients undergoing these procedures do not receive appropriate prophylaxis against VTE, often due to a disproportionate fear of bleeding complications in this population. Guidelines from the American College of Chest Physicians (ACCP) provide evidence-based recommendations for many aspects of VTE risk reduction in the setting of orthopedic surgery, as detailed in this review. The ACCP recommends the use of either low-molecular-weight heparin (LMWH), fondaparinux, or adjusted-dose warfarin as preferred VTE prophylaxis in patients undergoing either hip or knee arthroplasty. Fondaparinux is the preferred recommendation for patients undergoing hip fracture repair, followed by LMWH, unfractionated heparin, and adjusted-dose warfarin as alternative options. Extended-duration prophylaxis (for 4 to 5 weeks) is now recommended for patients undergoing hip arthroplasty or hip fracture repair. Patients undergoing knee arthroscopy do not require routine pharmacologic VTE prophylaxis.

Aspirin and other antiplatelet drugs in the prevention of venous thromboembolism

While there is good evidence for a protective effect of aspirin against occlusive vascular events in individuals with arterial disease, its role in preventing venous thromboembolism (VTE) is unclear. In this article we review the role of aspirin and other antiplatelet drugs in prevention of venous thromboembolism in surgical patients, high risk medical patients requiring aspirin for other reasons, patients with myeloproliferative disorders, long distance travellers and patients receiving treatment with the IMiD class of drugs. Overall, data from the PEP study and Anti-Platelet Trialists' systematic review show that aspirin reduces the risk of VTE by around 25% in high risk surgical patients. Data from retrospective and before/after studies also suggest efficacy in reducing VTE in myeloma patients on IMiD drugs in combination with dexamethasone or chemotherapy. However, there has been no direct comparison with coumarins or heparin to indicate that aspirin is the optimal form of thromboprophylaxis. In patients who require aspirin because of high risk of arterial vascular occlusion (including patients with polycythaemia vera and essential thrombocythaemia), the additional small reduction in VTE risk is an added benefit with no additional risk associated. There is no evidence for a role of aspirin in prevention of travel-related thrombosis. At present there is no clear evidence that aspirin is the drug of choice for the prevention of VTE in any patient group.

Prevention of Venous Thromboembolism after Acute Ischemic Stroke with Enoxaparin Versus Unfractionated Heparin and the Impact of Stroke Severity.

Background: Venous thromboembolism (VTE) prophylaxis with low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) is recommended in acute ischemic stroke patients, but most studies comparing LMWH and UFH are limited in methodology or sample size. The PREVAIL study was designed to assess the superiority of enoxaparin over UFH for VTE prophylaxis in acute ischemic stroke patients and to evaluate efficacy and safety according to stroke severity.Methods: Patients with acute ischemic stroke, confirmed by CT scan, and unable to walk unassisted due to motor impairment of the leg were enrolled in this prospective, open-label, parallel group, multicenter study. Patients from 15 countries were randomized within 48 h of stroke symptoms to receive enoxaparin 40 mg SC qd or UFH 5000 IU SC q12h for 10±4 days. Patients were stratified by NIH Stroke Scale score (NIHSS; severe ≥14, less severe <14). The primary efficacy endpoint was the composite of symptomatic or asymptomatic deep-vein thrombosis (DVT), symptomatic pulmonary embolism (PE), or fatal PE during treatment. DVT was confirmed primarily by venography, or ultrasonography when venography was not practical. PE was confirmed by VQ or CT scan, or angiography. Primary safety endpoints included clinically significant intracranial and major extracranial bleeding.Results: 1762 acute ischemic stroke patients were randomized. Characteristics were similar between groups; mean age was 66.0±12.9 yrs, mean NIHSS score was 11.3. In the efficacy population, enoxaparin (n=666) and UFH (n=669) were given for a mean of 10.5±3.2 days. Enoxaparin resulted in a 43% relative reduction in the risk of the primary efficacy endpoint compared with UFH (10.2% vs 18.1%; RR 0.57; 95% CI 0.44–0.76; p=0.0001, adjusted for NIHSS score). Incidences of VTE events are shown in Table 1. Reductions in the primary endpoint remained significant in patients with a NIHSS score ≥14 (16.3% vs 29.7%, p=0.0036) and <14 (8.3% vs 14.0%, p=0.0043). The composite of clinically significant intracranial and major extracranial bleeding was low and not significantly different between groups (Table 1).Conclusion: Enoxaparin 40 mg qd is superior to UFH q12h for reducing the risk of VTE in acute ischemic stroke patients, with no significant difference in clinically relevant bleeding. The reduction in VTE risk was consistent in patients with a NIHSS score ≥14 or <14.Table 1:Incidence of VTE and bleedingEndpointEnoxaparin n/N (%, 95% CI)UFH n/N (%, 95% CI)Symptomatic VTE2/666 (0.3, 0.0–0.7)6/669 (0.9, 0.2–1.6)Proximal DVT30/666 (4.5, 2.9–6.1)64/669 (9.6, 7.3–11.8)*Distal DVT44/666 (6.6, 4.7–8.5)85/669 (12.7, 10.2–15.2)*PE1/666 (0.2, 0.0–0.4)6/669 (0.9, 0.2–1.6)Composite of major extracranial and clinically significant intracranial bleeding11/877 (1.3, 0.5–1.9)6/872 (0.7, 0.1–1.2)*P<0.001