Anticoagulants For Treatment Of Venous Thromboembolism Research Articles

The risk of intracranial hemorrhage in glioma patients receiving anticoagulant treatment for venous thromboembolism: a bayesian network meta-analysis.

We aimed to perform a Bayesian network meta-analysis to assess the risk of intracranial hemorrhage (ICH) in patients with glioma receiving anticoagulant treatment for venous thromboembolism. The PubMed, Embase and Web of Science databases were searched for relevant publications until September 2022. All studies evaluating the risk of ICH in patients with glioma receiving anticoagulant treatment were included. Bayesian network meta-analysis and pairwise meta-analysis were performed to compare the ICH risk between the anticoagulant treatments. The Cochrane's Risk of Bias Tool and the Newcastle-Ottawa Scale (NOS) were used to evaluate the quality of studies. A total of 11 studies with 1301 patients were included. Pairwise comparisons showed no significant differences excepted with LMWH vs. DOACs (OR: 7.28, 95% CI: 2.11-25.17) and LMWH vs. Placebo (OR: 3.66, 95% CI: 2.15-6.24). For network meta-analysis, significant difference was found between patients treated with LMWH vs. Placebo (OR: 4.16, 95% CI: 2.00-10.14) and LMWH vs. DOACs (OR: 10.13, 95% CI: 2.70-70.19). It seems that LMWH has the highest risk of ICH in glioma patients, while no evidence indicates that DOACs increase the risk of ICH. The use of DOACs may perhaps be a better choice. Further larger studies focusing on the benefit-to-risk ratio are warranted.

Definitions of fatal bleeding in clinical studies evaluating anticoagulant treatment for venous thromboembolism: A scoping review

BackgroundFatal bleeding is a component of the primary safety outcome in most studies evaluating anticoagulation for venous thromboembolism (VTE), but a standardized definition for fatal bleeding is lacking. ObjectivesTo summarize definitions of fatal bleeding and describe the range of case-fatality rates of major bleeding in VTE studies. MethodsMEDLINE, Embase, and CENTRAL databases were searched from January 2008 to July 2021 for prospective studies that enrolled patients with VTE and evaluated the efficacy/safety of anticoagulation for VTE treatment or included fatal or major bleeding as primary outcome. Two authors independently performed study selection and data extraction. The primary outcome was the definition of fatal bleeding. The secondary outcome was the case-fatality rate of major bleeding. Data were analyzed using descriptive statistics. ResultsOf 4911 records identified, we included 132 articles representing 89 distinct studies. Twenty-seven (20%) articles and 7 of 89 (8%) studies reported a definition of fatal bleeding. Overall, we identified 3 different types of definitions that were either on the basis of a specific time interval between bleeding and death, bleeding location (intracranial) or clinical presentation (hemodynamic deterioration), or mainly relied on the judgment of the adjudication committee to determine the cause of death. The case-fatality rate of major bleeding ranged from 0 to 60% (median, 9.1%; interquartile range, 2.8%-18%). ConclusionLess than 10% of studies assessing anticoagulant treatment for VTE reported a definition for fatal bleeding. The lack of a (standardized) definition for fatal bleeding may lead to inaccurate estimates of the risk of fatal bleeding, particularly when compared across studies.

The risk of major bleeding in patients with factor V Leiden or prothrombin G20210A gene mutation while on extended anticoagulant treatment for venous thromboembolism

BackgroundThrombophilia predisposes to venous thromboembolism (VTE) because of acquired or hereditary factors. Among them, it has been suggested that gene mutations of the factor V Leiden (FVL) or prothrombin G20210A mutation (PGM) might reduce the risk of bleeding, but little data exist for patients treated using anticoagulants. ObjectivesTo assess whether thrombophilia is protective against bleeding. MethodsThis multicentre, multinational, prospective cohort study evaluated adults receiving long-term anticoagulants after a VTE event. We analyzed the incidence of major bleeding as the primary outcome, according to the genotype for FVL and PGM (wild-type and heterozygous/homozygous carriers). ResultsOf 2260 patients with genotype testing, during a median follow-up of 3 years, 106 patients experienced a major bleeding event (17 intracranial and 7 fatal). Among 439 carriers of FVL, 19 experienced major bleeding and there were no differences between any mutation vs wild-type (hazard ratio [HR], 0.89 [0.53-1.49]; p = .66). The comparison of major bleeding events between the 158 patients with any-PGM mutation (heterozygous or homozygous) vs wild-type also showed a nonstatistically significant difference with HR of 0.53 (0.19-1.43), p = .21. However, multivariate analysis demonstrated that major bleeds or clinically relevant nonmajor bleeding were statistically less likely for patients with either FVL and/or PGM compared with patients with both wild-type factor V and prothrombin genes (HR, 0.73; 95% CI = 0.55-0.97; p = .03). ConclusionThis study demonstrates that thrombophilia, defined as the presence of either FVL or the prothrombin G20210A mutation, is related with a lower rate of major/clinically relevant nonmajor bleeding while on anticoagulants in the extended treatment for VTE.

Anticoagulation for the initial treatment of venous thromboembolism in people with cancer.

Compared with people without cancer, people with cancer who receive anticoagulant treatment for venous thromboembolism (VTE) are more likely to develop recurrent VTE. To compare the efficacy and safety of three types of parenteral anticoagulants (i.e. fixed-dose low molecular weight heparin (LMWH), adjusted-dose unfractionated heparin (UFH), and fondaparinux) for the initial treatment of VTE in people with cancer. We performed a comprehensive search in the following major databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via Ovid) and Embase (via Ovid). We also handsearched conference proceedings, checked references of included studies, and searched for ongoing studies. This update of the systematic review is based on the findings of a literature search conducted on 14 August 2021. Randomised controlled trials (RCTs) assessing the benefits and harms of LMWH, UFH, and fondaparinux in people with cancer and objectively confirmed VTE. Using a standardised form, we extracted data - in duplicate - on study design, participants, interventions, outcomes of interest, and risk of bias. Outcomes of interest included all-cause mortality, symptomatic VTE, major bleeding, minor bleeding, postphlebitic syndrome, quality of life, and thrombocytopenia. We assessed the certainty of evidence for each outcome using the GRADE approach. Of 11,484 identified citations, 3073 were unique citations and 15 RCTs fulfilled the eligibility criteria, none of which were identified in the latest search. These trials enrolled 1615 participants with cancer and VTE: 13 compared LMWH with UFH; one compared fondaparinux with UFH and LMWH; and one compared dalteparin with tinzaparin, two different types of low molecular weight heparin. The meta-analyses showed that LMWH may reduce mortality at three months compared to UFH (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.40 to 1.10; risk difference (RD) 57 fewer per 1000, 95% CI 101 fewer to 17 more; low certainty evidence) and may reduce VTE recurrence slightly (RR 0.69, 95% CI 0.27 to 1.76; RD 30 fewer per 1000, 95% CI 70 fewer to 73 more; low certainty evidence). There were no data available for bleeding outcomes, postphlebitic syndrome, quality of life, or thrombocytopenia. The study comparing fondaparinux with heparin (UFH or LMWH) found that fondaparinux may increase mortality at three months (RR 1.25, 95% CI 0.86 to 1.81; RD 43 more per 1000, 95% CI 24 fewer to 139 more; low certainty evidence), may result in little to no difference in recurrent VTE (RR 0.93, 95% CI 0.56 to 1.54; RD 8 fewer per 1000, 95% CI 52 fewer to 63 more; low certainty evidence), may result in little to no difference in major bleeding (RR 0.82, 95% CI 0.40 to 1.66; RD 12 fewer per 1000, 95% CI 40 fewer to 44 more; low certainty evidence), and probably increases minor bleeding (RR 1.53, 95% CI 0.88 to 2.66; RD 42 more per 1000, 95% CI 10 fewer to 132 more; moderate certainty evidence). There were no data available for postphlebitic syndrome, quality of life, or thrombocytopenia. The study comparing dalteparin with tinzaparin found that dalteparin may reduce mortality slightly (RR 0.86, 95% CI 0.43 to 1.73; RD 33 fewer per 1000, 95% CI 135 fewer to 173 more; low certainty evidence), may reduce recurrent VTE (RR 0.44, 95% CI 0.09 to 2.16; RD 47 fewer per 1000, 95% CI 77 fewer to 98 more; low certainty evidence), may increase major bleeding slightly (RR 2.19, 95% CI 0.20 to 23.42; RD 20 more per 1000, 95% CI 14 fewer to 380 more; low certainty evidence), and may reduce minor bleeding slightly (RR 0.82, 95% CI 0.30 to 2.21; RD 24 fewer per 1000, 95% CI 95 fewer to 164 more; low certainty evidence). There were no data available for postphlebitic syndrome, quality of life, or thrombocytopenia. Low molecular weight heparin (LMWH) is probably superior to UFH in the initial treatment of VTE in people with cancer. Additional trials focusing on patient-important outcomes will further inform the questions addressed in this review. The decision for a person with cancer to start LMWH therapy should balance the benefits and harms and consider the person's values and preferences.

Apixaban and Dalteparin for the Treatment of Venous Thromboembolism in Patients with Different Sites of Cancer.

Efficacy and safety of anticoagulant treatment for venous thromboembolism (VTE) may vary in patients with different cancer sites. We evaluated the rates of VTE recurrence and major bleeding and the relative efficacy and safety of 6-month treatment with oral apixaban or subcutaneous dalteparin in patients with different cancer sites randomized in the Caravaggio study. Primary cancer was located at gastrointestinal sites in 375 patients (32.5%), lung in 200 (17.3%), breast in 155 (13.4%), genitourinary sites in 139 (12%), gynecological sites in 119 (10.3%), and was hematological in 85 patients (7.4%). Rates of VTE recurrence were 10.9% in patients with gynecological, 8.8% with gastrointestinal, 6.5% with genitourinary, and 5.5% with lung cancer with lower rates in the other sites of cancer. Rates of major bleeding were 7.2% in patients with genitourinary and 4.8% with gastrointestinal cancer, with lower rates in patients with other sites of cancer. The observed absolute risk difference in VTE recurrence in favor of apixaban was 11.9% in patients with gynecological, 5.5% with lung, 3.7% with genitourinary cancer, and 0.6% with gastrointestinal cancer. None of the risk differences was statistically significant. The rates of major bleeding in patients treated with apixaban or dalteparin was similar across patients with different cancer sites. In conclusion, recurrences appear to be more common in patients with gastrointestinal and gynecological cancer and major bleedings in patients with genitourinary and gastrointestinal cancer. Oral apixaban is a valid oral alternative to subcutaneous dalteparin for the treatment of a large spectrum of patients with cancer-associated VTE.

Anticoagulant treatment of venous thromboembolism in pregnant women

Venous thromboembolism (VTE), in particular pulmonary embolism (PE), remains the leading cause of death among pregnant women. Low-molecular-weight heparin (LMWH), with preference for therapeutic doses given twice daily according to European guidelines, is the drug of choice for the treatment of VTE in pregnancy and the puerperium. The recommended therapeutic dose is calculated on early pregnancy body weight. Evidence to support anti-Xa monitoring in pregnancy is weak. Unfractionated heparin (UFH) with multiple activated partial thromboplastin time measurements is still used in the acute treatment of high-risk PE. American experts have suggested considering initial outpatient therapy over hospital admission also in pregnant women with low-risk acute VTE, but European experts suggest adopting such a strategy selectively, for example in isolated distal leg thrombosis. Scheduled delivery with prior discontinuation of anticoagulant therapy in pregnant women who received a therapeutic dose of LMWH is suggested with the restart of therapy 4–6 h after a vaginal birth and 6–12 h after a cesarean delivery. It is recommended that UFH, LMWH, warfarin, acenocoumarol, or fondaparinux, but not direct-acting oral anticoagulants, should be used in breastfeeding women. This review summarizes the key messages from current guidelines mainly based on low-quality evidence and expert consensus.

Treatment and Secondary Prevention of Venous Thromboembolism in Real Clinical Practice Based on Health Care Professional Survey

Aim. To assess the duration of the anticoagulant treatment of venous thromboembolism (VTE) in various categories of patients in real clinical practice through survey of practitioners, as well as correspondence of the duration with current clinical guidelines.Material and methods. Data obtained from electronic survey of practicing surgeons as part of a commercial brand assessment (Brand Adoption Monitor) was studied. Survey was carried out by the "Validata” analytical agency at the request and with the financial support of Bayer. Inpatient and outpatient vascular surgeons, as well as general outpatient surgeons were invited to complete the electronic questionnaire. The number of interviewed specialists was 100: 50 inpatient vascular surgeons and 50 outpatient specialists, among whom the share of vascular surgeons (phlebologists, angi-ologists) was about 20%. The study was completed in 20 cities of Russia with a population of at least 200,000 people from all federal districts except the North Caucasus and the Republic of Crimea. The selection criteria for participants were: work experience in the specialty ≥3 years, work experience at the current organization >6 months, ≥5 patients with VTE during in the last month.Results. In total, 104 doctors were surveyed during the period from December 11, 2019 to January 20, 2020, of which 50 were inpatient vascular surgeons and 54 were from outpatient setting. According to the survey of vascular surgeons in hospitals, 75% (6 [5;10]) of patients were hospitalized with a primary episode of VTE and 25% (2 [1;4]) with a recurrent thrombotic event. In an outpatient surgeon, 27.5% (3 [2;5]) of patients were treated in an outpatient setting without hospitalization, 34.7% (3 [2;5]) came to an appointment immediately after discharge from the hospital and 38.8% (2 [1;4]) were a repeat visit regarding a previous VTE. Most often, surgeons observed episodes of clinically unprovoked VTE in 27.3% of cases, thrombotic events provoked by major transient risk factors were 12.2%, event provoked by small transient risk factors were 13.3% and events provoked by small persistent risk factors were 12.6%, while cancer-associated thrombosis represented 13.5%. Most surgeons chose to prescribe anticoagulant therapy beyond 3 months. About half of the specialists prescribed therapy for a year or longer for cancer-associated thrombosis and recurrent VTE. When treating the first episode of clinically unprovoked VTE, about half of the respondents chose anticoagulation for a period of 3 to 6 months. About 60% of specialists prescribed anticoagulant therapy for a period of 3 to 6 months to patients with minor transient or persistent risk factors and patients with VTE provoked by major transient risk factor (trauma or surgery).Conclusion. Correspondence of the duration of anticoagulant therapy in real clinical practice with the international clinical guidelines varies within 450% range and, on average, does not exceed 30%. This discrepancy was both in situations when the duration of therapy was lower than recommended, but also in situations when treatment extension would not have been recommended.

Anticoagulant treatment for venous thromboembolism: A pooled analysis and additional results of the XALIA and XALIA‐LEA noninterventional studies

BackgroundThe XALIA and XALIA‐LEA prospective, noninterventional studies investigated the safety and effectiveness of rivaroxaban versus standard anticoagulation for venous thromboembolism (VTE) treatment in routine clinical practice across global regions. ObjectivesThis pooled analysis combined their data to determine the incidence of thromboembolic and bleeding events in both treatment groups and addressed specific bleeding patterns in a broad range of patients. MethodsPatients with objectively confirmed VTE and an indication for ≥3 months’ anticoagulation treatment received rivaroxaban or standard anticoagulation (eg, initial treatment with heparin/fondaparinux, followed by a vitamin K antagonist [VKA]). Treatment choice, dose, management, and duration were at the physician’s discretion. Primary outcomes (major bleeding, recurrent VTE, and all‐cause mortality) were compared between the two treatment groups. Propensity score stratification, and matching were used to reduce bias due to confounding variables. ResultsOverall, 7129 patients were enrolled from 36 countries; 6445 and 2714 patients were included in the propensity score–stratified and –matched analyses, respectively. Major bleeding and incidences of recurrent VTE were similar between treatment groups; all‐cause mortality was lower with rivaroxaban than with standard anticoagulation. The incidences of genitourinary bleeding were higher with rivaroxaban than with standard anticoagulation therapy (46 and 23 events in the matched analysis, respectively). VKA management in real‐world practice was suboptimal. ConclusionXALIA and XALIA‐LEA show similar safety and effectiveness profiles of rivaroxaban and standard anticoagulation for VTE treatment in routine practice in many parts of the world. The observations are consistent with results from the phase III EINSTEIN randomized controlled trials.

Heavy menstrual bleeding in women on anticoagulant treatment for venous thromboembolism: Comparison of high‐ and low‐dose rivaroxaban with aspirin

BackgroundRivaroxaban may induce heavy menstrual bleeding. It is unknown if this effect is dose related or if rivaroxaban is associated with more menstrual bleeding than aspirin. ObjectivesTo demonstrate and compare menstrual patterns and actions taken among women receiving aspirin and two doses of rivaroxaban. MethodsThe EINSTEIN‐CHOICE trial compared once‐daily rivaroxaban 20 mg, rivaroxaban 10 mg, and aspirin 100 mg for extended treatment of venous thromboembolism in patients who had completed 6 to 12 months of anticoagulant therapy. In 362 women with menstrual cycles, menstrual flow duration and intensity assessed at days 30, 90, 180, and 360 were compared with those before starting anticoagulant therapy. ResultsMenstrual flow duration increased in 12%‐18% of the 134 women given 20‐mg rivaroxaban, in 6% to 12% of 120 women given 10‐mg rivaroxaban, and in 9% to 12% of 108 women given aspirin. Corresponding increases in flow intensity were 19% to 24%, 14% to 21%, and 13% to 20%. The odds ratios (ORs) for increased menstrual flow duration were 1.36 (95% confidence interval [CI], 0.62‐2.96) for rivaroxaban 20 mg versus aspirin, 0.77 (95% CI, 0.33‐1.81) for rivaroxaban 10 mg versus aspirin, and 0.57 (95% CI, 0.26‐1.25) for rivaroxaban 10 mg versus 20 mg. The ORs for increased menstrual flow intensity were 1.41 (95% CI, 0.67‐2.99), 1.07 (95% CI, 0.49‐2.34), and 0.76 (95% CI, 0.37‐ 1.57), respectively. ConclusionsThere were no statistically significant differences in menstrual hemorrhage patterns between women treated with 10 or 20 mg of rivaroxaban and aspirin. Compared with 10‐mg rivaroxaban or aspirin, 20‐mg rivaroxaban showed numerically more often increased menstrual flow duration and intensity. [Display omitted]

Pragmatic Recommendations for the Management of Anticoagulation and Venous Thrombotic Disease for Hospitalized Patients with COVID-19 in Low- and Middle-Income Countries.

ABSTRACTNew studies of COVID–19 are constantly updating best practices in clinical care. Often, it is impractical to apply recommendations based on high-income country investigations to resource limited settings in low- and middle-income countries (LMICs). We present a set of pragmatic recommendations for the management of anticoagulation and thrombotic disease for hospitalized patients with COVID-19 in LMICs. In the absence of contraindications, we recommend prophylactic anticoagulation with either low molecular weight heparin (LMWH) or unfractionated heparin (UFH) for all hospitalized COVID-19 patients in LMICs. If available, we recommend LMWH over UFH for venous thromboembolism (VTE) prophylaxis to minimize risk to healthcare workers. We recommend against the use of aspirin for VTE prophylaxis in hospitalized COVID-19 and non–COVID-19 patients in LMICs. Because of limited evidence, we suggest against the use of “enhanced” or “intermediate” prophylaxis in COVID-19 patients in LMICs. Based on current available evidence, we recommend against the initiation of empiric therapeutic anticoagulation without clinical suspicion for VTE. If contraindications exist to chemical prophylaxis, we recommend mechanical prophylaxis with intermittent pneumatic compression (IPC) devices or graduated compression stockings (GCS) for hospitalized COVID-19 patients in LMICs. In LMICs, we recommend initiating therapeutic anticoagulation for hospitalized COVID-19 patients, in accordance with local clinical practice guidelines, if there is high clinical suspicion for VTE, even in the absence of testing. If available, we recommend LMWH over UFH or Direct oral anticoagulants for treatment of VTE in LMICs to minimize risk to healthcare workers. In LMIC settings where continuous intravenous UFH or LMWH are unavailable or not feasible to use, we recommend fixed dose heparin, adjusted to body weight, in hospitalized COVID-19 patients with high clinical suspicion of VTE. We suggest D-dimer measurement, if available and affordable, at the time of admission for risk stratification, or when clinical suspicion for VTE is high. For hospitalized COVID-19 patients in LMICs, based on current available evidence, we make no recommendation on the use of serial D-dimer monitoring for the initiation of therapeutic anticoagulation. For hospitalized COVID-19 patients in LMICs receiving intravenous therapeutic UFH, we recommend serial monitoring of partial thromboplastin time or anti-factor Xa level, based on local laboratory capabilities. For hospitalized COVID-19 patients in LMICs receiving LMWH, we suggest against serial monitoring of anti-factor Xa level. We suggest serial monitoring of platelet counts in patients receiving therapeutic anticoagulation for VTE, to assess risk of bleeding or development of heparin induced thrombocytopenia.

The Effect of Anticoagulant Choice on Venous Thromboembolism Recurrence and Bleeding in Sickle Cell Disease

Patients with sickle cell disease (SCD) experience accelerated morbidity and mortality. Venous thromboembolism (VTE), a risk factor for early mortality in SCD, occurs in 11-12% of patients with SCD by the age of 40. While indefinite anticoagulation is indicated in the SCD population, there is limited understanding of comparative efficacy and hemorrhagic risk of individual anticoagulation agents in this population. We reviewed the use of anticoagulation for treatment of VTE in patients with SCD at our institution to begin to address these questions. A retrospective chart review of all patients with SCD 18 years of age and older (currently alive or deceased) who received care at Boston Medical Center/Boston University between 2003 and 2018 was performed. VTE was defined as deep venous thrombosis (DVT) diagnosed by duplex ultrasound or pulmonary embolism (PE) diagnosed by either ventilation-perfusion scanning or computed tomography angiography. The primary efficacy outcome was the number of VTE events which occurred while the patient was receiving anticoagulation. The primary safety outcome was major bleeding as defined by the International Society on Thrombosis and Hemostasis 2005 guidelines. The medical records of 233 patients with SCD were reviewed; VTE was identified in 55 (23.6%) patients. Sixty-five percent were female. In these 55 patients, a total of 94 VTE events occurred. Fifteen (16.0%) were catheter-associated upper extremity DVTs. For the first event, initial outpatient treatment consisted of warfarin in 56%, low-molecular-weight heparin (LMWH) in 18.2%, rivaroxaban in 9.1%, apixaban in 5.5%, and fondaparinux in 3.6%. The median length of treatment was 7.3 (median: 6, IQR: 3-12) months. Recurrent VTEs occurred in 27 (49%) patients with a total of 39 recurrent events. Among the recurrent events, thirteen (33.0%) were treatment failures occurring during anticoagulation therapy (see Table 1): 7 of 37 (18.9%) on warfarin, 2 of 20 (10.0%) on LMWH, and 4 of 15 (26.7%) on rivaroxaban. Death from recurrent VTE occurred in two patients; one occurred while a patient was therapeutic on warfarin. Major bleeding occurred in two patients (3.6%); in both cases, this was intracranial hemorrhage while on warfarin. In this retrospective study, there was a high rate of VTE recurrence despite anticoagulation in patients with SCD. Treatment failure was highest with warfarin and rivaroxaban, although adherence was difficult to assess. Risk of hemorrhage and death appears higher in those prescribed warfarin. These data affirm the need for long-term anticoagulation in most patients with SCD with a VTE and support the use of direct oral anticoagulants as a first-line agent. Disclosures Sloan: Abbvie: Other: Endpoint Review Committee; Stemline: Consultancy; Merck: Other: endpoint review commitee.

Abstract 4: Disparities in the Use of Direct Oral Anticoagulant Treatment of Venous Thromboembolism in the United States, 2010-2016

Background: Venous thromboembolism (VTE) occurs in approximately 100 persons per 100,000 each year in the United States, and for decades warfarin had been the mainstay of therapy. However, beginning in 2012 direct oral anticoagulants (DOAC) were approved for treatment and prevention of VTE, and are now recommended as first-line therapy. We assessed the factors associated with direct oral anticoagulant use among commercially-insured VTE patients. Methods: We performed a retrospective cohort analysis of adult patients with an incident diagnosis of VTE between 01/01/2010 and 12/01/2016 using OptumInsight’s Clinformatics Data Mart, a large US health care claims database. We identified the first filled anticoagulant prescription within 30 days of discharge, as well as baseline demographic and socioeconomic characteristics for all VTE patients with available prescription data. We then performed a multivariate logistic regression, adjusting for age, sex, race/ethnicity, region of residence, household net worth, prescribing provider specialty, and clinical covariates to identify factors associated with the use of direct oral anticoagulants. Results: There were 12,390 patients included in the analysis. In adjusted multivariate analyses, there was no difference in the use of DOAC among men and women (OR 0.99, 95% CI 0.91 - 1.08, p=0.80). Black patients were less likely to receive a DOAC compared to white patients (OR 0.86, 95% CI 0.76 - 0.98, p=0.020). There were no differences in the utilization among Asian patients (OR 1.21, 95% CI 0.83 - 1.75, p=0.324) or Hispanic patients (OR 1.04, 95% CI 0.88 - 1.23, p=0.66) as compared to white patients. Conclusion: Although DOAC adoption has increased steadily, among a commercially-insured population, black race was independently associated with the use of warfarin as compared to DOAC for incident VTE despite controlling for other socioeconomic factors. This finding was not present among Asian or Hispanic patients. This suggests the possibility of a racial disparity in access to this new pharmacotherapy.

Update on diagnosis and anticoagulant therapy for venous thromboembolism.

Venous thromboembolism (VTE) continues to be a common medical problem requiring the need for rapid treatment with anticoagulant therapy. Until the recent availability of the direct oral anticoagulants for treatment of VTE, the option for oral anticoagulation was limited to warfarin therapy. The addition of these new medications has been welcomed, but has led to added complexities in deciding the most appropriate agent for each patient based on individual risk factors. Furthermore, there are several circumstances where optimal duration of therapy is not well established. This article will focus on the diagnosis of VTE, the choice of anticoagulant and treatment duration.

Patients' Satisfaction with Anticoagulant Treatment for Venous Thromboembolism

Background: Data on treatment expectation and perception towards vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs), and low molecular weight heparins (LMWH) for the management of venous thromboembolism (VTE) are sparse.Methods: Prospective observational study including subjects admitted to the hospital with a diagnosis of VTE and a prescription of VKA, DOAC, or a LMWH. Treatment expectations, convenience and satisfaction were assessed using the Perception of anticoagulant treatment questionnaire (PACT-Q) at baseline and at three months.Results: A total of 140 patients were included. Treatment expectations regarding ease of use and the ability to self-manage anticoagulation therapy were higher in patients on DOACs. However, overall treatment satisfaction scores were similar at three months between the groups.Conclusion: Patients with VTE who are prescribed an anticoagulant have different expectations at baseline, but appear to have similar treatment satisfaction regardless of the type of anticoagulant prescribed.

Anticoagulation for the initial treatment of venous thromboembolism in people with cancer.

Compared with people without cancer, people with cancer who receive anticoagulant treatment for venous thromboembolism (VTE) are more likely to develop recurrent VTE. To compare the efficacy and safety of three types of parenteral anticoagulants (i.e. fixed-dose low molecular weight heparin (LMWH), adjusted-dose unfractionated heparin (UFH), and fondaparinux) for the initial treatment of VTE in people with cancer. A comprehensive search included a major electronic search of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) (2018, Issue 1), MEDLINE (via Ovid) and Embase (via Ovid); handsearching of conference proceedings; checking of references of included studies; use of the 'related citation' feature in PubMed; and a search for ongoing studies. This update of the systematic review was based on the findings of a literature search conducted on 14 January 2018. Randomized controlled trials (RCTs) assessing the benefits and harms of LMWH, UFH, and fondaparinux in people with cancer and objectively confirmed VTE. Using a standardized form, we extracted data in duplicate on study design, participants, interventions outcomes of interest, and risk of bias. Outcomes of interested included all-cause mortality, symptomatic VTE, major bleeding, minor bleeding, postphlebitic syndrome, quality of life, and thrombocytopenia. We assessed the certainty of evidence for each outcome using the GRADE approach. Of 15440 identified citations, 7387 unique citations, 15 RCTs fulfilled the eligibility criteria. These trials enrolled 1615 participants with cancer and VTE: 13 compared LMWH with UFH enrolling 1025 participants, one compared fondaparinux with UFH and LMWH enrolling 477 participants, and one compared dalteparin with tinzaparin enrolling 113 participants. The meta-analysis of mortality at three months included 418 participants from five studies and that of recurrent VTE included 422 participants from 3 studies. The findings showed that LMWH likely decreases mortality at three months compared to UFH (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.40 to 1.10; risk difference (RD) 57 fewer per 1000, 95% CI 101 fewer to 17 more; moderate certainty evidence), but did not rule out a clinically significant increase or decrease in VTE recurrence (RR 0.69, 95% CI 0.27 to 1.76; RD 30 fewer per 1000, 95% CI 70 fewer to 73 more; moderate certainty evidence).The study comparing fondaparinux with heparin (UFH or LMWH) did not exclude a beneficial or detrimental effect of fondaparinux on mortality at three months (RR 1.25, 95% CI 0.86 to 1.81; RD 43 more per 1000, 95% CI 24 fewer to 139 more; moderate certainty evidence), recurrent VTE (RR 0.93, 95% CI 0.56 to 1.54; RD 8 fewer per 1000, 95% CI 52 fewer to 63 more; moderate certainty evidence), major bleeding (RR 0.82, 95% CI 0.40 to 1.66; RD 12 fewer per 1000, 95% CI 40 fewer to 44 more; moderate certainty evidence), or minor bleeding (RR 1.53, 95% CI 0.88 to 2.66; RD 42 more per 1000, 95% CI 10 fewer to 132 more; moderate certainty evidence)The study comparing dalteparin with tinzaparin did not exclude a beneficial or detrimental effect of dalteparin on mortality (RR 0.86, 95% CI 0.43 to 1.73; RD 33 fewer per 1000, 95% CI 135 fewer to 173 more; low certainty evidence), recurrent VTE (RR 0.44, 95% CI 0.09 to 2.16; RD 47 fewer per 1000, 95% CI 77 fewer to 98 more; low certainty evidence), major bleeding (RR 2.19, 95% CI 0.20 to 23.42; RD 20 more per 1000, 95% CI 14 fewer to 380 more; low certainty evidence), or minor bleeding (RR 0.82, 95% CI 0.30 to 2.21; RD 24 fewer per 1000, 95% CI 95 fewer to 164 more; low certainty evidence). LMWH is possibly superior to UFH in the initial treatment of VTE in people with cancer. Additional trials focusing on patient-important outcomes will further inform the questions addressed in this review. The decision for a person with cancer to start LMWH therapy should balance the benefits and harms and consider the person's values and preferences.

Quality of Life in Cancer Patients Undergoing Anticoagulant Treatment for Venous Thromboembolism: The Quavitec Study

Introduction: Treatment and prevention of VTE is crucial, yet anticoagulation is under-prescribed in cancer patients. The recommended treatment for established VTE in cancer patients is low molecular weight heparin (LMWH) once daily for at least 3 months, and termination or continuation of treatment after 3-6 months is still based on individual evaluation of the benefit-risk ratio, tolerability, drug availability, patient preference, and cancer. Despite important concerns about long-term patient tolerance for LMWH treatment (after 10 days) and its side effects, no study has analyzed the overall impact of LMWH on quality-of-life (QoL) in cancer patients.Methods: In this prospective, longitudinal, multicenter study, consecutive eligible adult cancer patients (>18 years), diagnosed with either deep vein thrombosis or a pulmonary embolism (PE), were recruited at participating centers between February 2011 and 2012. Patients were asked to answer three questionnaires administered at time of VTE diagnosis (M0), and 3 (M3) and 6 (M6) months after start of anticoagulant treatment: 1) the Medical Outcome Study 36-item Short-Form Health Survey (MOS SF-36) for generic Health-Related Quality of Life (HRQoL), 2) the European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire, and 3) the Venous Insufficiency Epidemiological and Economic Study (VEINES)-QOL questionnaire.Results (median[iqr], Wilcoxon Signed Rank Test): At M0, 400 cancer patients (51.5% female) were included, 60.4% with metastatic disease and 67.0% on chemotherapy. The choice of anticoagulant was made by the attending physician. 88.75% of patients received LMWH, 5.5% a vitamin K antagonist, 1.5% unfractionated heparin, and 3.75% a direct oral anticoagulant. Throughout the study, 18.9% of patients on LMWH reported at least one side effect with injection (number of reports: pain, 26 (7.3%); ecchymosis, 57(16.1%); pruritis, 2(0.6%); nodules, 28 (7.9%)). Mortality rate was 24.73%, with 79 deaths attributable to cancer progression and 3 to VTE.At M3, patients on LMWH showed a significant increase of 3.9 [5.7-14 ] points in the MOS SF-36 global HRQoL score (p=0.0007) and 8.3 [-8.3;17] points in the EORTC global Health status/QoL survey (p=0.0001). The veinsQoL score decreased by 2 [-5.2-4] points (p=0.022). Logistic regression analysis identified predictive factors common to both MOS SF-36 and EORTC: ECOG scores (MOS SF-36, p=0.050; EORTC, p=0.006) and whether patients were ambulatory as opposed to bedridden (MOS SF-36, p=0.001; EORTC, p=0.019). Cancer surgery (p=0.005), presence of central venous catheter (CVC) (p=0.018) or PE (p=0.029), and absence of chemotherapy (p=0.017), or acute infection (p=0.048) were also positive predictors of cancer-related QoL in the EORTC survey. No predictive factors were identified for veinsQoL.At M6, patients on LMWH showed sustained point increases of 5.5 [-5.6; 22] in the MOS SF-36 global HRQoL score (p<0.0001) and 8.3 [-8.3;33] in the EORTC global Health status/QoL score (p<0.0001), with no change in VeinsQoL. Logistic regression identified the pattern of change in QoL in the first three months of anticoagulation as a strong predictor of QoL scores at the M6 follow-up (MOS SF-36, p<0.0001; EORTC, p<0.0001; veinesQoL, p<0.0001). Tumor histology (p=0.005), CVC (p=0.024), absence of acute infection (p=0.034), and being ambulatory as opposed to bedridden (p=0.045), were additional predictive factors in the MOS SF-36.There was no change in the MOS SF-36 global HRQoL score between 3 and 6 months, but there was significant improvement in the sub-dimensions of general health (1.9 pts, p=0.057) and vitality (3.7 pts; p=0.016). The improved global health status/QoL score in the EORTC was also maintained between 3 and 6 months, with a significant 4.7 point reduction in the fatigue symptom subscale (p=0.016). No change was observed in the VeinsQoL. Painful side effects of LMWH treatment did not predict diminished QoL in the logistic regression analysis. Cancer progression was a negative predictor of MOS SF-36 global HRQoL in these patients (p=0.051).Conclusion: In cancer patients with established VTE who survive to 3 and 6 month follow-ups under recommended anticoagulant treatment, QoL increases despite long term treatment with LMWH. This analysis is the first to show that LMWH treatment from 3 to 6 months does not diminish QoL in cancer patients diagnosed with VTE. DisclosuresNo relevant conflicts of interest to declare.

LMWH in cancer patients with renal impairment – better than warfarin?

Venous thromboembolism (VTE) is one of the leading causes of death in cancer patients, which are known to have a 5- to 7-fold increased risk for VTE. The anticoagulant treatment of VTE in cancer patients is less effective with a three-fold increased risk of VTE recurrence compared to non-cancer patients, and it is less safe with more than double rates of major bleeding. Compared to vitamin-K antagonists (VKA), long-term secondary prevention with low molecular weight heparin (LMWH) has been shown to reduce the risk of recurrent VTE in cancer-associated thrombosis (CAT), and therefore, current international guidelines recommend the use of LMWH over VKA. With increasing age, cancer prevalence and VTE incidence increase while renal function decreases. Anti-cancer treatment may impair renal function additionally. Therefore, renal insufficiency is a frequent challenge in CAT patients, which is associated with a higher risk of both bleeding and recurrent VTE. Both VKA and LMWH may be associated with less efficacy and higher bleeding risk in renal insufficiency. Unfortunately, there is a lack of prospective data on renal insufficiency and CAT. A recent sub-analysis from a large randomized controlled trial shows that the bleeding risk in patients with severe renal insufficiency in CAT is not elevated with the use of LMWH compared to VKA while efficacy is maintained. In addition, LMWH treatment has several practical advantages over VKA, particularly in patients with CAT while they are receiving anti-cancer treatment.

Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer.

Compared with patients without cancer, patients with cancer who receive anticoagulant treatment for venous thromboembolism (VTE) are more likely to develop recurrent VTE. To compare the efficacy and safety of three types of parenteral anticoagulants (i.e. fixed-dose low molecular weight heparin (LMWH), adjusted-dose unfractionated heparin (UFH), and fondaparinux) for the initial treatment of VTE in patients with cancer. A comprehensive search for studies of anticoagulation in patients with cancer including a February 2013 electronic search of: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and ISI Web of Science. Randomized clinical trials (RCTs) comparing LMWH, UFH, and fondaparinux in patients with cancer and objectively confirmed VTE. Using a standardized data form, review authors extracted data in duplicate on methodologic quality, participants, interventions, and outcomes of interest that included mortality, recurrent VTE, major bleeding, minor bleeding, postphlebitic syndrome, quality of life, and thrombocytopenia. Of 9559 identified citations, 16 RCTs were eligible: 13 compared LMWH with UFH, two compared fondaparinux with heparin, and one compared dalteparin with tinzaparin. Meta-analysis of 11 studies showed a statistically significant reduction in mortality at three months of follow-up with LMWH compared with UFH (risk ratio (RR) 0.71; 95% confidence interval (CI) 0.52 to 0.98). There was little change in the effect estimate after excluding studies of lower methodologic quality (RR 0.72; 95% CI 0.52 to 1.00). A meta-analysis of three studies comparing LMWH with UFH showed no statistically significant reduction in VTE recurrence (RR 0.78; 95% CI 0.29 to 2.08). The overall quality of evidence was low for LMWH versus UFH due to imprecision and likely publication bias. There were no statistically significant differences between heparin and fondaparinux for the outcomes of mortality (RR 1.27; 95% CI 0.88 to 1.84), recurrent VTE (RR 0.95; 95% CI 0.57 to 1.60), major bleeding (RR 0.79; 95% CI 0.39 to1.63), or minor bleeding (RR 1.50; 95% CI 0.87 to 2.59). The one study comparing dalteparin with tinzaparin found no statistically significant difference in mortality (RR 0.86; 95% CI 0.43 to 1.73). LMWH is possibly superior to UFH in the initial treatment of VTE in patients with cancer. Additional trials focusing on patient-important outcomes will further inform the questions addressed in this review.

Rivaroxaban

Rivaroxaban

EINSTEIN transforms anticoagulant therapy in acute PE

The EINSTEIN-PE trial showed that rivaroxaban has equal efficacy and a lower rate of bleeding than coumarins in the treatment of acute pulmonary embolism. We anticipate regulatory and consumer acceptance for rivaroxaban, representing the first new anticoagulant treatment for venous thromboembolism since the introduction of warfarin compounds 50 years ago.