Treatment Of Acute Venous Thromboembolism Research Articles

Statins during Anticoagulation for Emergency Life-Threatening Venous Thromboembolism: A Review.

Venous thromboembolism (VTE) is the leading cause of morbidity and death worldwide, after cancer and cardiovascular diseases. VTE is defined to include pulmonary embolism (PE) and/or deep vein thrombosis (DVT). Approximately 25% of PE patients experience sudden death as an initial symptom of VTE, and between 10% and 30% of patients die within the first month after diagnosis. Currently, the only drugs approved for the treatment of both acute and chronic VTE are vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). However, their effectiveness is limited due to their associated risk of bleeding. Ideally, therapy should be able to treat VTE and limit the risk of VTE recurrence without increasing the risk of bleeding. Several studies have shown that the use of statins during anticoagulation for VTE reduces the risk of death and VTE recurrence. However, to date, there are conflicting data on the impact of statins during anticoagulation for VTE. A biological protective function of statins during anticoagulation has also been reported. Statins affect D-dimer levels; tissue factor (TF) gene expression; and VIII, VII, and Von Willebrand clotting factors-the major clotting factors they are able to affect. However, the usefulness of statins for the treatment and prevention of VTE is currently under debate, and they should not be substituted for guideline-recommended VTE prophylaxis or anticoagulation treatment. In this review of the literature, we illustrate the advances on this topic, including data on the role of statins in primary VTE prevention and secondary VTE prevention, related biological mechanisms, the risk of bleeding during their use, and their ability to reduce the risk of death.

Efficacy and Safety of Direct Oral Anticoagulants for Acute Treatment of Venous Thromboembolism in Older Adults: A Network Meta-Analysis of Randomised Controlled Trials.

This systematic review and network meta-analysis aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in adults aged 75 and over undergoing acute venous thromboembolism (VTE) treatment. PubMed, Embase and the CENTRAL were searched up to 25 December 2023. The incidence of VTE recurrence and bleeding events was assessed. Employing a frequentist network meta-analysis approach, interventions not directly compared could be indirectly assessed through the 95% confidence interval (CI), enhancing the interpretability of the search results. The surface under the cumulative ranking curves (SUCRA) was utilized to generate the relative ranking probabilities for each group. Our study, analysing 6 randomised controlled trials with 3665 patients, compares direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in adults aged 75 and over with acute venous thromboembolism. Edoxaban reduces VTE recurrence risk compared with VKAs (risk ratio [RR] .50, 95% CI 0.27 - .95), while apixaban significantly decreases bleeding risk compared with VKAs (RR .23, 95% CI 0.08 - .69), edoxaban (RR .28, 95% CI 0.09 - .86) and rivaroxaban (RR .28, 95% CI 0.09 - .86). Despite low overall evidence quality, apixaban consistently ranks highest for both efficacy and safety. Findings underscore the nuanced efficacy-safety balance in this population, emphasizing cautious interpretation due to evidence limitations. Apixaban emerges as a favourable choice for acute VTE treatment in the elderly, displaying reduced bleeding risk compared to other treatments while maintaining comparable efficacy. Future studies should explore diverse anticoagulants efficacy and safety in older populations. Additionally, clinical prediction models tailored to geriatric cohorts are crucial for guiding treatment duration decisions.

Retrospective, multicenter analysis of the safety and effectiveness of direct oral anticoagulants for the treatment of venous thromboembolism in obesity.

Direct oral anticoagulants (DOACs) are the preferred treatment for venous thromboembolism (VTE). However, DOAC use in patients with a BMI greater than 40kg/m2 has not been well studied despite the growing prevalence of obesity, and current literature is often underpowered. This multicenter, retrospective, observational study evaluated patients 18 years and older who received DOACs for acute VTE treatment. Patients receiving DOACs for recurrent VTE or for failure of another agent were excluded. The primary efficacy outcome was recurrent VTE and the primary safety outcome was major bleeding within 12 months (or one month after stopping anticoagulation therapy). A propensity score analysis was performed to balance patient characteristics and evaluate the primary endpoints by BMI group. Time-to-event outcomes were analyzed using weighted Kaplan-Meier curves. There were 165 patients with a BMI of at least 40kg/m2 and 320 patients with a BMI less than 40kg/m2. The majority received apixaban (373, 77%). Recurrent VTE occurred in 5 (3.0%) and 13 (4.1%) of patients in the higher and lower BMI groups, respectively (adjusted OR: 0.66; 95% CI: 0.16-2.69). Major bleeding occurred in 5 (3.0%) and 15 (4.7%) of patients in the higher and lower BMI groups, respectively (adjusted OR: 1.19; 95% CI: 0.36-3.92). There was no significant difference in VTE recurrence or major bleeding related to BMI among patients treated with DOACs. This study showed that DOACs may be a safe and effective VTE treatment option in patients with obesity.

Dabigatran for Treatment and Secondary Prevention of Venous Thromboembolism in Pediatric Congenital Heart Disease.

Congenital heart disease (CHD) is common in children and associated with greater risk of thrombotic complications. Management of these complications with standard-of-care treatment is suboptimal for these children. The effectiveness and safety of dabigatran were demonstrated in pivotal pediatric studies for the treatment of acute venous thromboembolism (VTE; NCT01895777) and secondary VTE prevention (NCT02197416). We report safety and efficacy outcomes from subgroup analyses of these studies for children with CHD (diagnosed according to local practice) and those without. In NCT01895777, 17/21 (81.0%) and 16/27 (59.3%) patients with CHD (including cyanotic) treated with dabigatran and standard of care, respectively, met the primary end point (complete thrombus resolution, freedom from recurrent VTE, and freedom from VTE-related death; odds ratio [OR], 0.34 [95% CI, 0.08-1.23]). In patients without CHD, 41.0% (n=64) versus 34.9% (n=22) achieved this end point with the respective treatments (OR, 0.77 [95% CI, 0.42-1.41]). Although numerical differences were observed, no heterogeneity in treatment effect of dabigatran on the composite primary end point was detected in patients with and without CHD (interaction P =0.2674). In NCT02197416, recurrent VTE at 12 months occurred in 0/17 patients with CHD versus 3/194 (1.5%) without. No patient with CHD experienced major or clinically relevant nonmajor bleeding events. Data on favorable anticoagulant alternatives for the unmet needs of children with CHD are emerging, and our exploratory results suggest that dabigatran could be an appropriate treatment choice, although challenging sample size limitations in pediatric studies require cautious interpretation of findings. URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01895777, NCT02197416.

Safety of dabigatran

Thrombosis ranks first among the leading causes of death worldwide and is a fatal risk factor for patients’ health. Rapid diagnosis and appropriate treatment are necessary. There are three categories of antithrombotic agents: antiplatelet agents, anticoagulants, and fibrinolytics. Anticoagulants are first-line therapy for the prevention and treatment of venous thrombi. Dabigatran etexilate is a direct thrombin inhibitor. The effectiveness of dabigatran has been demonstrated in several clinical studies for the prevention of venous thromboembolism in patients undergoing total hip or total knee arthroplasty, for the prevention of stroke in patients with non-valvular atrial fibrillation, and in the treatment of acute venous thromboembolism. Some studies have demonstrated that the use of dabigatran leads to an increased risk of bleeding. Therefore, the purpose of this review is to examine the safety of dabigatran in patients over 18 years of age. We identified potentially relevant studies by searching the electronic databases PubMed, Web of Science, Cochrane Library, MEDLINE, and Google Scholar. Further, according to the inclusion and exclusion criteria, as well as by means of independent selection, all the authors of this article selected the sources that were suitable according to the criteria and compiled this review.

Use and Outcomes of Secondary Anticoagulation in Patients <21 Years Old Following Completion of a Primary Course of Anticoagulation for Treatment of Acute Provoked VTE: Findings from the Multinational Kids-DOTT Trial

Background: Although the rate of venous thromboembolism (VTE) recurrence is low among pediatric patients with provoked VTE, children with a history of VTE who have persistent prothrombotic risk factors such as central venous catheters (CVCs), thrombophilia and cancer have been shown to have increased risk for recurrent VTE (e.g., Brandao et al., Lancet Hematology 2020). Prospective multicenter data on the use of secondary anticoagulation in patients with a first provoked VTE are limited. Objective: We sought to characterize the use and outcomes of secondary anticoagulation in patients <21 years old with provoked VTE, via the multinational Kids-DOTT trial. We hypothesized that older patient age is associated with use of secondary anticoagulation among patients with provoked VTE who have persistent prothrombotic risk factors following completion of a primary course of anticoagulation for treatment of acute provoked VTE, and that frequencies of clinically relevant bleeding and recurrent VTE are low in this setting. Methods: We conducted a secondary analysis of patients enrolled in the NIH-sponsored, multinational randomized controlled Kids-DOTT trial (NCT00687882; Goldenberg et al., JAMA 2022) who received secondary anticoagulation. We defined secondary anticoagulation as anticoagulant use beyond the initial treatment period of 6-12 weeks for the purpose of secondary VTE prevention, as captured in case report forms. “Chronic” secondary anticoagulation was defined as that which began within 2 weeks of the prescribed treatment course; otherwise, secondary anticoagulation was defined as “episodic”. The presence of new and/or recurrent prothrombotic risk factors was captured in association with each episode. Variables were summarized as counts and percentages for categorical variables and medians with interquartile ranges (IQR) for continuous variables. To compare groups that did versus did not receive secondary anticoagulation, Mann-Whitney U test was used for continuous variables and chi-square, or Fisher's exact test was used for categorical variables, with alpha <0.05 considered significant. All statistical analyses were performed using R version 4.1.2 (R Core Team, 2021). Results: Among 532 patients enrolled in the Kids-DOTT trial, 18 (3.4%) received secondary anticoagulation, all of whom had persistence or recurrence of prothrombotic risk factors (Table 1). The most frequent prothrombotic risk factors associated with use of secondary anticoagulation were a new or persistent central venous catheter (28%, N=5) and infection (17%, N=3). Despite having persistence or recurrence of prothrombotic risk factors, only 1 patient who received secondary anticoagulation developed recurrent VTE and 2 patients experienced clinically relevant bleeding during a median follow-up of 1.99 years [IQR 1.06-2.02], none of which was temporally related to secondary anticoagulation use. As shown in Table 2, patients who received secondary anticoagulation were older (median 12.9 years [IQR 7.6-15.5 years] vs. 8 years [1-15 years], P=0.05) and more likely to have upper extremity deep vein thrombosis (50% vs. 29%; P=0.003) when compared to those who did not receive secondary anticoagulation. Conclusion: These findings suggest that use of secondary anticoagulation is low among patients <21 years old with provoked VTE. However, among those who receive secondary anticoagulation for persistent or recurrent prothrombotic risk factors, the risks of recurrent VTE and clinically relevant bleeding may be low. Furthermore, focused study of use and outcomes of chronic and episodic secondary anticoagulation is warranted to inform future practice on secondary prevention in children, adolescents, and young adults with a history of provoked VTE.

Clinical Characteristics, Treatment, and Outcomes of Provoked Acute Cerebral Sinovenous Thrombosis in Patients

Background Cerebral sinus venous thrombosis (CSVT) is a rare pediatric condition with an estimated incidence of 0.7 per 100,000 children. However, amongst pediatric venous thromboembolism (VTE), the proportion of CSVT is high, at about 10% of all pediatric VTE. Key risk factors include perinatal stressors in cases of neonatal CSVT and acute infections, especially head and neck infections, in older children. To date, few multinational trials of pediatric VTE treatment have reported findings specifically among CSVT patients. Aims We sought to describe the clinical characteristics, treatment strategies, and outcomes of the patients with provoked acute CSVT enrolled in the Kids-DOTT trial and to compare these features to those of Kids-DOTT participants with non-CSVT VTE. Methods Kids-DOTT was an NIH-sponsored multinational randomized clinical trial (RCT) comparing 6 weeks vs. 3 months of anticoagulation for provoked acute VTE treatment in patients <21 years, with two non-randomized cohort arms run in parallel to the RCT for patients with persistent antiphospholipid antibodies or complete veno-occlusion at 6 weeks post-diagnosis of the index VTE. The primary RCT findings were recently published. In the present analysis, descriptive statistics were used to summarize patient and thrombus characteristics, treatments, and outcomes, and variables were compared between CSVT and non-CSVT VTE groups using Mann-Whitney U test for continuous variables and Chi-squared or Fisher's exact test, as appropriate, for categorical variables. All statistical analyses were performed using R Core Team, 2021. A P-value of <0.05 was considered statistically significant. Results Among 532 patients enrolled in the Kids-DOTT trial, the index VTE was a CSVT in 75 (14%). Age distribution differed significantly ( P=0.002) between CSVT and non-CSVT VTE patients, with the CSVT more likely to occur in neonates and children, compared to non-CSVT VTE more likely to occur in adolescents. CSVT was less likely to be CVC-related compared to non-CSVT VTE. The frequency of any infection (56.9% vs 26%, p<0.001) and specifically infection of the head/neck (35.4% vs 2%; P<0.001) as a provoking factor was significantly higher for CSVT vs. non-CSVT VTE. Non-head and neck infections were less likely to be associated with CSVT compared to non-CSVT VTE. One-third of CSVT patients received 6 weeks, while two-thirds received > 3 months, of anticoagulation (Table 2). No patients developed ISTH-defined symptomatic recurrent VTE or clinically relevant bleeding. Conclusions These multinational trial findings substantiate those of retrospective studies implicating head/neck infection as an important provoking factor for CSVT in young patients. The absence of recurrent VTE or clinically relevant bleeding among CSVT patients managed with anticoagulation in Kids-DOTT serve to augment recent RCT findings of CSVT treatment in children involving direct oral anticoagulants, demonstrating the safety and efficacy of therapeutic anticoagulation for pediatric CSVT.

A framework to characterise the reproducibility of meta-analysis results with its application to direct oral anticoagulants in the acute treatment of venous thromboembolism.

The number of meta-analyses of aggregate data has dramatically increased due to the facility of obtaining data from publications and the development of free, easy-to-use, and specialised statistical software. Even when meta-analyses include the same studies, their results may vary owing to different methodological choices. Assessment of the replication of meta-analysis provides an example of the variation of effect 'naturally' observed between multiple research projects. Reproducibility of results has mostly been reported using graphical descriptive representations. A quantitative analysis of such results would enable (i) breakdown of the total observed variability with quantification of the variability generated by the replication process and (ii) identification of which variables account for this variability, such as methodological quality or the statistical analysis procedures used. These variables might explain systematic mean differences between results and dispersion of the results. To quantitatively characterise the reproducibility of meta-analysis results, a bivariate linear mixed-effects model was developed to simulate both mean results and their corresponding uncertainty. Results were assigned to several replication groups, those assessing the same studies, outcomes, treatment indication and comparisons classified in the same replication group. A nested random effect structure was used to break down the total variability within each replication group and between these groups to enable calculation of an intragroup correlation coefficient and quantification of reproducibility. Determinants of variability were investigated by modelling both mean and variance parameters using covariates. The proposed model was applied to the example of meta-analyses evaluating direct oral anticoagulants in the acute treatment of venous thromboembolism.

Direct Oral Anticoagulants in The Treatment Of Acute Venous Thromboembolism in Patients With Obesity: A Systematic Review With Meta-Analysis

Direct Oral Anticoagulants in The Treatment Of Acute Venous Thromboembolism in Patients With Obesity: A Systematic Review With Meta-Analysis

Apixaban versus rivaroxaban for treatment of acute deep venous thrombosis in patients with cancer.

12113 Background: Direct oral anticoagulants (DOAC) such as Apixaban and Rivaroxaban are increasingly used for the treatment of acute venous thromboembolism (VTE) over traditional vitamin K antagonists. Malignant neoplasms predispose to acute VTE and clinical management necessitates anticoagulation to prevent further complications. We compare Apixaban to Rivaroxaban for the treatment of acute VTE in the setting of malignancy with the endpoint of chronic deep venous thrombosis (DVT) development after 2 years. Methods: The TriNetX Research network was used for this study. TriNetX provides access to anonymized medical record information on more than 107 million patients in 76 large healthcare organizations. Two cohorts were created for this study using the International Classification of Disease-10 (ICD-10) codes. All patients were required to have a diagnosis of breast (C50), lung (C34), colon (C18), or prostate cancer (C61). All were diagnosed with acute deep venous thrombosis (DVT) of the lower extremities (I82.409). One cohort was treated with rivaroxaban while the other was treated with apixaban within 3 days of DVT diagnosis. Each cohort was excluded from being treated with the other anticoagulant. The cohorts were balanced for age, race, gender, and ethnicity, then evaluated for the development of chronic DVT (I82.509) within the subsequent twelve months. Results: The development of chronic DVT was significantly more common in the apixaban cohort, with a risk ratio of 1.36 (95% CI (1.12,1.65), p-value 0.0015). See table. Conclusions: Patients with acute VTE in the setting of malignancy were at a significantly higher risk of developing chronic DVT following treatment with Apixaban compared to those who received Rivaroxaban at 2 years post-treatment. These results may contribute to increased discussion between physicians and patients when deciding between these two direct oral anticoagulants for the management of acute VTE. Diagnosis of chronic DVT in cancer patients treated with apixaban and rivaroxaban. [Table: see text]

Real world experience of efficacy and safety of rivaroxaban in paediatric venous thromboembolism

IntroductionPaediatric clinical practice for treatment of venous thromboembolism (VTE) is based on extrapolation from adult trials with minimal data on anticoagulation efficacy and safety in children. Based on EINSTEIN-Jr clinical trial data, rivaroxaban was approved to treat VTE and prevent its recurrence in children of all ages. AimTo report the safety and efficacy of rivaroxaban use in paediatric VTE and to present real-world data, specifically about very young children. MethodsWe conducted a retrospective observational study at Birmingham Children's Hospital. Data were collected from patients <16 years old who received rivaroxaban after its licensure in the period between March 2021 and June 2022. ResultsRivaroxaban was used for treatment of acute VTE in 64 patients. Thrombosis was CVC-related in 26 patients, unprovoked in 3, while the rest had one or more risk factors for VTE. Safety and efficacy of rivaroxaban were assessed in 52 patients after excluding patients who were on current rivaroxaban treatment and those who were lost to follow up or stopped rivaroxaban due to intolerance. No bleeding events were reported, and recurrence of thrombosis occurred in only 3.6 %. About 35 % had normalised re-imaging, 40.3 % improved, 9.6 % were unchanged and 11.5 % stopped rivaroxaban without re-imaging. Rivaroxaban was used for secondary VTE prophylaxis in 6 patients in our cohort with no recurrence of thrombosis or bleeding reports. ConclusionsOur real-world experience confirmed that rivaroxaban was well tolerated, effective and safe. Further real-world data and observational studies are essential to investigate the use of rivaroxaban among different risk groups.

Direct oral anticoagulants in pediatric venous thromboembolism: Experience in specialized pediatric hemostasis centers in the United States

BackgroundBefore the official US Food and Drug Administration approval in 2021, pediatric hematologists across the United States have used direct oral anticoagulants (DOACs) “off-label” and based on extrapolation from labeling for adults with venous thromboembolism (VTE) and interim results of pediatric-specific DOAC clinical studies. ObjectivesThe American Thrombosis and Hemostasis Network 15 (ATHN 15) study aimed to characterize the use of DOACs from 2015 to 2021 at 15 specialized pediatric hemostasis centers in the United States, with emphasis on safety and effectiveness. MethodsEligible participants were those aged 0 to 21 years who had a DOAC included as part of their anticoagulation regimen for the treatment of acute VTE or secondary prevention of VTE. Data were collected for up to 6 months after initiation of the DOAC. ResultsA total of 233 participants were enrolled, with a mean age of 16.5 years. Rivaroxaban was the most commonly prescribed DOAC (59.1%) followed by apixaban (38.8%). Thirty-one (13.8%) participants reported bleeding complications while on a DOAC. Major or clinically relevant nonmajor bleeding events occurred in 1 (0.4%) and 5 (2.2%) participants, respectively. Worsening menstrual bleeding was reported in 35.7% of females aged >12 years and occurred more frequently in those using rivaroxaban (45.6%) compared with apixaban (18.9%). The recurrent thrombosis rate was 4%. ConclusionPediatric hematologists at specialized hemostasis centers in the United States have been using DOACs for the treatment and prevention of VTEs, primarily in adolescents and young adults. Reported DOAC use showed adequate safety and effectiveness rates.

Direct oral anticoagulants versus low-molecular-weight heparins for the treatment of acute venous thromboembolism in patients with gastrointestinal cancer: a systematic review and meta-analysis

BackgroundThe association between gastrointestinal (GI) cancer and a high incidence of venous thromboembolism (VTE) is well known. Previous randomized controlled studies demonstrated that direct oral anticoagulants (DOACs) effectively treat cancer-associated thrombosis (CAT). However, some DOACs appeared to increase the risk of bleeding, particularly in patients with GI malignancies. Therefore, the current systematic review and meta-analysis were conducted to evaluate the safety and efficacy of DOACs in GI cancer-associated thrombosis.MethodsTwo investigators individually reviewed all studies that compared DOACs and low-molecular-weight heparins (LMWHs) in GI cancer-associated thrombosis and were published in MEDLINE and EMBASE before February 2022. The effect estimates and 95% confidence intervals (CIs) from each eligible study were combined using the Mantel–Haenszel method.ResultsA total of 2226 patients were included in the meta-analysis. The rates of major bleeding in the DOAC and LMWH groups were not significantly different (relative risk [RR]: 1.31; 95% CI: 0.84–2.04; P = 0.23; I2 = 41%). However, the rate of clinically relevant nonmajor bleeding (CRNMB) was significantly higher in the DOAC group (RR: 1.76; 95% CI: 1.24–2.52; P = 0.002; I2 = 8%). The risks of recurrent VTE in the groups did not significantly differ (RR: 0.72; 95% CI: 0.49–1.04; P = 0.08; I2 = 0%).ConclusionsThe current data suggest that treatment of GI cancer-associated thrombosis with DOACs significantly increases the risk of CRNMB. However, the risk of major bleeding was not significantly different. The efficacy of DOACs for preventing recurrent VTE in GI cancer was comparable to that of LMWHs.Trial registrationINPLASY202180113.

Model-informed bridging of rivaroxaban doses for thromboprophylaxis in pediatric patients aged 9 years and older with congenital heart disease.

Rivaroxaban is approved in various regions for the treatment of acute venous thromboembolism (VTE) in children aged between 0 and 18 years and was recently investigated for thromboprophylaxis in children aged between 2 and 8 years (with body weights <30 kg) with congenital heart disease who had undergone the Fontan procedure. In the absence of clinical data, rivaroxaban doses for thromboprophylaxis in post‐Fontan children aged 9 years and older or ≥30 kg were derived by a bridging approach that used physiologically‐based pharmacokinetic (PBPK) and population pharmacokinetic (popPK) models based on pharmacokinetic (PK) data from 588 pediatric patients and from adult patients who received 10 mg once daily for thromboprophylaxis after major orthopedic surgeries as a reference. Both models showed a tendency toward underestimating rivaroxaban exposure in post‐Fontan patients aged between 2 and 5 years but accurately described rivaroxaban PK in post‐Fontan patients aged between 5 and 8 years. Under the assumption that hepatic function is not impaired in post‐Fontan patients, PBPK and popPK simulations indicated that half of the rivaroxaban doses for the same body weight given to pediatric patients treated for acute VTE would yield in pediatric post‐Fontan patients exposures similar to the exposure observed in adult patients receiving 10 mg rivaroxaban once daily for thromboprophylaxis. Simulation‐derived doses (7.5 mg rivaroxaban once daily for body weights 30–<50 kg and 10 mg once daily for body weights ≥50 kg) were therefore included in the recent US label of rivaroxaban for thromboprophylaxis in children aged 2 years and older with congenital heart disease who have undergone the Fontan procedure.

Deep vein thrombosis and pulmonary embolism : Diagnosis and treatment

This review summarizes current evidence and guideline recommendations concerning diagnosis and treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). For the diagnostic pathway, evidence-based algorithms should be employed, based on the assessment of pretest clinical probability. D‑dimer tests may reduce the need for subsequent diagnostic procedures. Clinical management of PE is guided by risk stratification according to early mortality. Lactate levels may be helpful for further risk stratification. The acute treatment of venous thromboembolism (VTE) is commenced with intensified anticoagulation (AC), either with parenteral AC or higher initial doses of apixaban or rivaroxaban. All patients with VTE should receive the anticoagulation maintenance therapy for 3-6months, while the duration of the subsequent secondary prophylaxis depends on the presumed risk of VTE recurrence and bleeding. Compression therapy is used to prevent postthrombotic syndrome. Acute revascularization procedures are limited to rare special cases. In obese patients up to 150 kg, standard doses of rivaroxaban and apixaban are appropriate. In cancer-associated thromboembolism (CAT), the previous guideline recommendation to use low molecular weight heparin (LMWH) for 3-6months is now broadened with the recommendation for factor Xa inhibitors, with the caveat for gastrointestinal and urothelial cancer or expected drug-drug interactions with the anticancer treatment. Here, and in unstable clinical situations, LMWH is preferred.

Effectiveness and Safety of Oral Anticoagulants in the Treatment of Acute Venous Thromboembolism: A Nationwide Comparative Cohort Study in France.

Introduction Data from clinical trials indicate that direct oral anticoagulants (DOACs) are noninferior and safer than conventional therapy (low-molecular-weight heparin followed by a vitamin K antagonist [VKA]) for treating venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism (PE). This study compared the effectiveness and safety of DOACs and conventional therapy in a real-world setting. Methods This observational study used French national claims data of adult, treatment-naïve patients diagnosed with VTE (majority PE) who were hospitalized and treated for VTE with a DOAC (apixaban or rivaroxaban) or VKAs during 2013 to 2018. Patients with active cancer were excluded. After propensity score matching for each DOAC-VKA comparison, risks of bleeding, recurrent VTE, and all-cause mortality were compared at 6 months. Cox proportional hazards regression was used to estimate adjusted hazard ratios of the endpoints. Results A total of 58,137 patients were included (10,775 VKAs, 10,440 apixaban, 36,922 rivaroxaban). Propensity score-matched cohort sizes were 7,503 for apixaban and 9,179 for rivaroxaban. The hazard ratio (95% confidence interval) was significantly lower for apixaban than VKAs for bleeding requiring hospitalization (0.43 [0.32–0.59]), all-cause death (0.61 [0.51–0.74]), and first recurrent VTE (0.67 [0.52–0.85]). The hazard ratio was also significantly lower for rivaroxaban than VKAs for all-cause death (0.63 [0.53–0.74]) but not for bleeding requiring hospitalization (0.86 [0.69–1.07]) or first recurrent VTE (0.91 [0.74–1.13]). Conclusion Apixaban was associated with superior safety and effectiveness than VKAs. All-cause mortality was lower in both DOACs than VKAs. Our results support recommendations to use DOACs over VKAs for the treatment of VTE.

Comparative efficacy and safety of oral anticoagulants for the treatment of venous thromboembolism in the patients with different renal functions: a systematic review, pairwise and network meta-analysis

ObjectivesTo compare the efficacy and safety of direct oral anticoagulants (DOACs) in patients with venous thromboembolism (VTE) and different renal functions.DesignSystematic review containing pairwise and Bayesian network meta-analysis of randomised...

Ibero-American Society of Interventionism (SIDI) and the Spanish Society of Vascular and Interventional Radiology (SERVEI) Standard of Practice (SOP) for the Management of Inferior Vena Cava Filters in the Treatment of Acute Venous Thromboembolism.

Objectives: to present an interventional radiology standard of practice on the use of inferior vena cava filters (IVCFs) in patients with or at risk to develop venous thromboembolism (VTE) from the Iberoamerican Interventional Society (SIDI) and Spanish Vascular and Interventional Radiology Society (SERVEI). Methods: a group of twenty-two interventional radiologist experts, from the SIDI and SERVEI societies, attended online meetings to develop a current clinical practice guideline on the proper indication for the placement and retrieval of IVCFs. A broad review was undertaken to determine the participation of interventional radiologists in the current guidelines and a consensus on inferior vena cava filters. Twenty-two experts from both societies worked on a common draft and received a questionnaire where they had to assess, for IVCF placement, the absolute, relative, and prophylactic indications. The experts voted on the different indications and reasoned their decision. Results: a total of two-hundred-thirty-three articles were reviewed. Interventional radiologists participated in the development of just two of the eight guidelines. The threshold for inclusion was 100% agreement. Three absolute and four relative indications for the IVCF placement were identified. No indications for the prophylactic filter placement reached the threshold. Conclusion: interventional radiologists are highly involved in the management of IVCFs but have limited participation in the development of multidisciplinary clinical practice guidelines.

Long-term VTE treatment with rivaroxaban: Results from the DRESDEN NOAC REGISTRY

Data on long-term effectiveness and safety of venous thromboembolism (VTE) treatment with rivaroxaban are scarce and not available from randomized clinical trials. To supplement the positive results of phase III VTE treatment trials with rivaroxaban, we used data from the ongoing, prospective, non-interventional DRESDEN NOAC REGISTRY to evaluate long-term management patterns and clinical outcomes.Between December 1st 2011 and September 30th 2020, 812 patients with acute VTE (575 DVT; 237 PE) and rivaroxaban treatment were prospectively followed. During treatment (median rivaroxaban exposure 1.1 years IQR 0.3–5.0 years; median follow-up 6.1 years IQR 4.7–7.8 years) rates of recurrent VTE and ISTH major bleeding were 0.7/100 pt. years (95% CI 0.4–1.1) and 2.1/100 pt. years; 95% CI 1.5–2.8, respectively. Of the 427 patients still taking rivaroxaban at 12 months, 276 and 202 were still taking rivaroxaban at 3 and 5 years, respectively. “Scheduled end of treatment” was the leading discontinuation reason also beyond 12 months. When exposure days were divided by the number of major clinical outcomes (recurrent VTE + other major cardiovascular + ISTH major bleeding), continued rivaroxaban treatment had the longest “exposure per event” period (6398 days/event) compared to patients switching to alternative treatments (4658 days/event) or stopping anticoagulation completely (4337 days/event).Our results confirm low thrombotic and major bleeding rates for long-term VTE treatment with rivaroxaban. Beyond 12 months, scheduled treatment discontinuations still occur. Although 3–5% of patients planned for indefinite rivaroxaban therapy switched to other anticoagulants each year, the overall persistence to rivaroxaban was high.

Efficacy and Safety of Tinzaparin in CAT Patients with Hematological Malignancy

IntroductionIn patients with hematological cancers, the high risk of bleeding raises serious concerns when anticoagulant therapy is initiated for treatment of acute venous thromboembolism (VTE). In the CATCH trial, we showed that tinzaparin is associated with a significantly lower risk of clinically relevant bleeding (CRB) and clinically relevant non-major bleeding (CRNMB) compared with warfarin therapy in patients with a solid tumor or hematological cancer. Hence, we performed a post-hoc analysis to assess the risk of recurrent VTE (rVTE) and bleeding in the hematological cancer patient subgroup. Risk factors associated with rVTE and bleeding were also explored.MethodsCATCH (ClinicalTrials.govNCT01130025; Lee A et al. JAMA 2015) was a Phase III, multinational, randomized, active-controlled, open-label trial. Patients with solid tumors or hematological malignancies were randomized to receive therapeutic dosing of tinzaparin (175 IU/kg OD) vs warfarin (INR target 2.0 - 3.0) for treatment of acute VTE. Treatment was given for up to 6 months but was withheld during periods of severe thrombocytopenia (platelet count < 50 x 10 9/L). The primary efficacy outcome was the composite of symptomatic deep vein thrombosis (DVT), symptomatic nonfatal pulmonary embolism (PE), fatal PE, incidental proximal DVT and incidental proximal PE. All thrombosis and bleeding outcomes, including rPE, rDVT, major bleeding (MB), CRB, and CRNMB were objectively documented and centrally adjudicated in a treatment-blinded fashion. Patients with myeloma, lymphoma or leukemia were included in this sub-group analysis. Treatment effect was assessed by means of a cox-regression with time to first event as outcome and deaths not due to fatal PE as a competing risk factor. The cumulative incidence functions and the corresponding 95% CIs were estimated.Results94 of 900 subjects (10.4%) in CATCH had a hematological cancer. Of these patients, 44 and 50 received tinzaparin and warfarin, respectively. The most common hematological cancer was lymphoma (59.6%), followed by myeloma (30.9%), chronic leukemia (5.3%) and acute leukemia (4.3%). rVTE occurred in fewer patients assigned to tinzaparin versus warfarin (2.4% vs 6.4%) but this difference was not statistically significant (HR 0.36; 95%CI 0.04-3.14). All recurrent thrombotic events were PE; no rDVT occurred. Also, trends for less bleeding with tinzaparin were noted for MB (tinzaparin 0.0% versus warfarin 5.0%), CRB (tinzaparin 10.4% vs warfarin 23.5%; HR 0.53; 95%CI 0.15-1.83) and CRNMB (tinzaparin 10.4% vs warfarin 19.5%; HR 0.69; 95%CI 0.19-2.51). 3 patients in each treatment arm had a fatal bleeding event and there was no difference in overall mortality (tinzaparin 22.7% vs warfarin 22.0%). There were no risk factors associated with rVTE identified. Factors associated with CRB in patients with hematological cancer included the use of antiplatelet agents (HR 7.63; 95%CI 1.17-49.6; p=0.033) and renal insufficiency (HR 12.4; 95%CI 2.15-72.0; p=0.005).ConclusionIn this post-hoc subgroup analysis of patients with hematological cancers who received anticoagulation for acute VTE, tinzaparin may be a more effective and safer alternative to warfarin. Randomized controlled trials are warranted to test this hypothesis in this challenging population with a high risk of bleeding. [Display omitted] DisclosuresLee: Leo Pharma: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Servier: Consultancy, Honoraria. Bauersachs: Bayer: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; LEO Pharma: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau. Janus: LEO Pharma: Current Employment. Leeder: LEO Pharma: Current Employment. Thoning: LEO Pharma: Current Employment. Khorana: Anthos: Consultancy, Honoraria; Halozyme: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria.