Recurrent Venous Thromboembolism Events Research Articles

Pharmacologic Anticoagulation Is Associated With a Lower Risk of Recurrent Venous Thromboembolic Events During Janus Kinase Inhibitor Use for Patients With a Prior Thrombosis.

Janus kinase (JAK) inhibitors tofacitinib and upadacitinib are effective therapies for inflammatory bowel disease and rheumatologic disorders but currently possess a warning for increased venous thromboembolism (VTE) risk. Some patients with a history of VTE may benefit from a JAK inhibitor, but the risk of recurrent VTE with JAK inhibitor use is unclear. Our goal was to observe rates of new VTE events after starting JAK inhibitor therapy in patients with a prior VTE, and observe whether concurrent anticoagulation (AC) reduces this risk. We conducted a review of adults prescribed tofacitinib or upadacitinib between January 1, 2000, and June 30, 2023, with a prior history of VTE. Patient charts were reviewed for demographic data, disease type, and VTE date(s), and to verify duration of JAK inhibitor use along with any concurrent AC. VTEs following JAK inhibitor initiation were identified by International Classification of Diseases-Tenth Revision code and verified by physician documentation and imaging. We identified 79 patients with a documented VTE history before initiating JAK inhibitors, 47 of whom began a JAK inhibitor with concurrent AC. Of these, 15 patients discontinued AC while receiving JAK inhibitors. In total, 5 new VTE events were observed during 55.42 patient-years of JAK inhibitor treatment without concurrent AC (9.0 events per 100 patient-years), while no new VTE events occurred during 65.2 patient-years of JAK inhibitor treatment with concurrent AC, demonstrating a lower risk of recurrent VTE (P = .020). These results suggest that for patients with a prior VTE history there is a high risk for recurrent VTE while receiving JAK inhibitors. Concurrent use of AC with JAK inhibitors appears to be protective against recurrent VTEs in this population.

Risk of recurrent venous thromboembolism and bleeding in patients with acute isolated subsegmental pulmonary embolism

IntroductionApproximately 10 % of all diagnosed pulmonary embolism are isolated to the subsegmental vessels. The risk of recurrent venous thromboembolism (VTE) in patients with an acute subsegmental pulmonary embolism (SSPE) managed with or without anticoagulant therapy remains poorly understood. MethodsThis is an observational cohort study including consecutive adult patients diagnosed with acute isolated SSPE between June 01, 2019, and August 31, 2022. We excluded patients with a concomitant diagnosis of deep vein thrombosis and those who had an indication for long-term anticoagulation. The primary outcome was objectively confirmed recurrent VTE. ResultsOverall, 118 patients with acute SSPE were included in the analysis. The mean (± standard deviation [SD]) age of the participants was 59 ± 17 years and 44 % of them had active cancer. Mean (±SD) duration of follow-up was 438 ± 426 days. Seventy-seven patients (65 %) were initially treated with anticoagulation, whereas 41 patients (35 %) were not. Of the 77 patients receiving anticoagulant therapy, 23 (30 %) received extended-duration anticoagulation (beyond 3 months) for secondary prevention. Overall, recurrent VTE events occurred in 6/118 (5 %, 95 % CI 2.4 to 10.7) patients. Four events (4/77 = 5.2 %, 95 % CI 2.0 to 12.6) occurred in initially treated patients. Two recurrent VTE occurred in patients initially left untreated (2/41 = 4.9 %, 95 % CI 1.4 to 16.1). Half of the recurrent VTE occurred in patients with active cancer. ConclusionsMost patients diagnosed with an acute SSPE received anticoagulation. The incidence of recurrent VTE detected over time was relatively high, especially in patients with cancer.

Comparison of Clinical Outcomes in Patients with Active Cancer Receiving Rivaroxaban or Low-Molecular-Weight Heparin: The OSCAR-UK Study.

In most patients with cancer-associated venous thromboembolism (CT), essentially those not at high risk of bleeding, guidelines recommend treatment with direct oral anticoagulants as an alternative to low-molecular-weight heparins (LMWHs). Population-based studies comparing these therapies are scarce. To compare the risk of venous thromboembolism (VTE) recurrences, significant bleeding, and all-cause mortality in patients with CT receiving rivaroxaban or LMWHs. Using UK Clinical Practice Research Datalink data from 2013 to 2020, we generated a cohort of patients with first CT treated initially with either rivaroxaban or LMWH. Patients were observed 12 months for VTE recurrences, significant bleeds (major bleeds or clinically relevant nonmajor bleeding requiring hospitalization), and all-cause mortality. Overlap weighted sub-distribution hazard ratios (SHRs) compared rivaroxaban with LMWH in an intention-to-treat analysis. The cohort consisted of 2,259 patients with first CT, 314 receiving rivaroxaban, and 1,945 LMWH, mean age 72.4 and 66.9 years, respectively. In the 12-month observational period, 184 person-years following rivaroxaban and 1,057 following LMWH, 10 and 66 incident recurrent VTE events, 20 and 102 significant bleeds, and 10 and 133 deaths were observed in rivaroxaban and LMWH users, respectively. The weighted SHR at 12 months for VTE recurrences in rivaroxaban compared with LMWH were 0.80 (0.37-1.73); for significant bleeds 1.01 (0.57-1.81); and for all-cause mortality 0.49 (0.23-1.06). Patients with CT, not at high risk of bleeding, treated with either rivaroxaban or LMWH have comparable effectiveness and safety outcomes. This supports the recommendation that rivaroxaban is a reasonable alternative to LMWH for the treatment of CT.

Recurrent Venous Thromboembolism in Patients on Anticoagulation: An Update Based on the Revised AWMF S2k Guideline.

In the recently updated German S2k Guideline "Diagnostics and Therapy of Venous Thrombosis and Pulmonary Embolism," a new chapter was incorporated about recurrent venous thromboembolism (VTE) in patients on anticoagulation treatment. Despite the high efficacy of anticoagulation in most patients, approximately 2% experience a recurrent VTE event while receiving anticoagulant drugs. The proper diagnosis of the recurrent VTE is important and possible only with the knowledge of localization and thrombus burden of the primary VTE event. Possible reasons for recurrent VTE events in patients on anticoagulation are non-adherence to medication, sub-therapeutic drug levels due to resorption disorders or drug interactions, or concomitant disease with high thrombogenicity. Cancer is the most common underlying disease, but it is important to investigate and understand possible other causes whenever a breakthrough VTE event occurs. This results in the recommendation that in patients with VTE recurrence on therapeutic anticoagulation, in particular, the presence of malignant disease, antiphospholipid syndrome, and rare diseases like paroxysmal nocturnal hemoglobinuria or Behçet's disease should be considered. For VTE recurrence during heparin therapy, heparin-induced thrombocytopenia type II needs to be ruled out, even if platelet counts are within the normal range. Although the mechanisms of recurrence on anticoagulation can be evaluated in a certain degree, clinical evidence for the management of recurrent VTE in anticoagulated patients is minimal and mainly based on expert opinion. Switching anticoagulant medication and intensifying anticoagulant treatment are possible options.

Hormonal contraceptive use after a first venous thrombotic event and the risk of recurrence in premenopausal women

BackgroundExtensive evidence is available on hormonal contraceptive (HC) use and the risk of a first venous thromboembolism (VTE) event. Despite recommendations to discontinue combined HC (CHC) use, some women continue or start its use after a first VTE. ObjectivesWe aimed to evaluate the VTE recurrence risk associated with HC use in premenopausal women. MethodsPremenopausal women with a first VTE included in the Multiple Environmental and Genetic Assessment of Venous Thrombosis study between 1999 and 2004 were followed for a recurrence until 2010. Data on HC use were available through linkage to the Dutch Foundation for Pharmaceutical Statistics. The risk of recurrence was assessed 1) during anticoagulant therapy and 2) after cessation of anticoagulant therapy. Time-dependent Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs adjusted for age and body mass index at baseline and thromboprophylaxis use during follow-up. ResultsSix hundred fifty women were uniquely linked and followed for a total of 3538 person-years (median, 6.1 years), during which 57 VTE recurrences occurred. Five occurred (8.8%) during anticoagulation treatment, with no clear risk difference for CHC use vs nonuse (HR, 0.8; 95% CI, 0.1-8.2). After anticoagulation cessation, CHC use was associated with a 2.4-fold higher risk of recurrence (HR, 2.4; 95% CI, 1.2-5.0) compared with nonuse. Recurrence risk for levonorgestrel-releasing intrauterine device use was similar to that for nonuse (HR, 0.9; 95% CI, 0.3-3.1). ConclusionCHC use after a first VTE is safe during anticoagulant use but substantially increases the risk of a recurrent VTE event in absence of anticoagulant use. This study adds to the evidence regarding the use of a levonorgestrel-releasing intrauterine device as a safe alternative.

Does anticoagulation in combination with immunosuppressive therapy prevent recurrent thrombosis in Behçet's disease?

Vascular involvement in Behçet's disease (BD) occurs in up to 50% of patients. The main mechanism of thrombosis is inflammation. Thus, immunosuppressants (IS) are the mainstay of therapy, and adding anticoagulation (AC) is controversial. In daily practice, we observed that patients who received AC in combination with IS experienced less recurrent thrombosis and decided to investigate our BD patients retrospectively. We hypothesized that adding AC to immunosuppressive therapy may lower the risk of recurrent thrombosis. Treatment at the time of first or recurrent thrombotic events was recorded. Events under the only IS and IS + AC treatments were compared. There were 40 patients (33 males). The most common types of first vascular events were deep vein thrombosis (77.5%) followed by pulmonary embolism (PE) (52.5%). One patient did not receive any treatment. Among the 39 patients, 32 received glucocorticoid and at least one of the azathioprine, or cyclophosphamide, anti-TNF, 5 received monotherapy with azathioprine, 1 received monotherapy with corticosteroid, and the remaining 1 received monotherapy with cyclophosphamide. In total, 22 patients (55%) experienced 27 recurrent venous thromboembolism (VTE) events. Two (7.4%) events while only on AC, 2 (7.4%) events while on AC + IS, and 15 (55.5%) events occurred while on only IS. Eight (19.6%) patients were not receiving any treatment during relapses. The recurrence rate was statistically significantly lower in the IS + AC treatment group compared to IS alone. In conclusion, IS are the mainstay of treatment for BD, and adding AC may help to lower the recurrence risk of thrombotic events.

Early Time Courses of Recurrent Venous Thromboembolism and Bleeding during Apixaban or Dalteparin Therapy for Patients with Cancer.

In patients with acute venous thromboembolism (VTE), the rates of recurrence and major bleeding are highest during the first weeks of anticoagulation. The CARAVAGGIO trial demonstrated noninferiority of apixaban to dalteparin for treatment of cancer-associated VTE without an increased risk of major bleeding. We compared the early time course of VTE recurrence and major bleeding events of apixaban compared with dalteparin at 7, 30, and 90 days of treatment in patients with cancer-associated VTE. The study design of the CARAVAGGIO trial has been described. Eligible patients were randomly assigned to receive monotherapy with either apixaban or dalteparin for 6 months. The primary efficacy outcome was the incidence of objectively confirmed recurrent VTE. The primary safety outcome was major bleeding. In 1,155 patients, recurrent VTE after 7, 30, and 90 days occurred in 6 (1%), 15 (2.6%), and 27 (4.7%) patients in the apixaban arm versus 5 (0.9%), 20 (3.5%), and 36 (6.2%) patients respectively in the dalteparin arm. By day 7, 30, and 90, major bleeding events had occurred in 3 (0.5%), 9 (1.6%), and 16 (2.8%) patients in the apixaban group versus 5 (0.9%), 11 (1.9%), and 17 (2.9%) patients in the dalteparin group. The frequencies of recurrent VTE and major bleeding events at 7, 30, and 90 days of apixaban compared with dalteparin were similar in patients with cancer-associated VTE. This supports the use of apixaban for the initiation and early phase of anticoagulant therapy in cancer-associated VTE.

Kidney disease in antiphospholipid antibody syndrome

Antiphospholipid syndrome (APS) is a rare autoimmune disease characterized by recurrent arterial and venous thromboembolic events. Renal complications occur in 3 % of patients. Renal artery stenosis is the most common, and APS-related nephropathy is the predominant microvascular complication. APS nephropathy has heterogeneous manifestations ranging from hematuria and non-nephrotic range proteinuria to hypertension and multi-organ failure caused by catastrophic antiphospholipid antibody syndrome. Anticoagulation and thromboprophylaxis are key to management. Immunosuppression has been used with some success but lacks randomized controlled trial validation for their use.

Efficacy and safety of rivaroxaban versus apixaban for venous thromboembolism: A systematic review and meta-analysis of observational studies.

Direct-acting oral anticoagulants (DOACs) including rivaroxaban and apixaban are preferred over vitamin K antagonists for the treatment of venous thromboembolism (VTE). We conducted a systematic review and a meta-analysis to compare the efficacy and safety of rivaroxaban versus apixaban in the treatment of VTE. We conducted an electronic search for studies that directly compared treatment with rivaroxaban and apixaban in adult patients with VTE. The relative risks (RRs) and 95% confidence intervals (CIs) were estimated and pooled using a fixed-effect model unless significant heterogeneity was present (I2 > 40%), then random-effects model was used. The primary efficacy and safety outcomes were recurrent VTE (rVTE) and major bleeding events, respectively. Nine observational studies were included in our meta-analysis, assessing 24,156 patients for apixaban and 38,847 for rivaroxaban. Pooling of data for our primary efficacy outcome showed a trend towards lower risk of rVTE with apixaban compared to rivaroxaban (RR 0.77, 95% CI 0.57-1.04, I2 = 53%). Analysis of our primary safety outcome showed a significantly lower risk of major bleeding with apixaban compared to rivaroxaban (RR 0.68, 95% CI 0.61-0.76, I2 = 0%). Apixaban was associated with significantly decreased risk of net clinical harm, clinically relevant non major bleeding (CRNMB) and any bleeding, compared to rivaroxaban (RR 0.75, 95% CI 0.61-0.92, I2 = 50%; RR 0.58, 95% CI 0.50-0.67, I2 = 7%; RR 0.64, 95% CI 0.59-0.70, I2 = 0%, respectively). Apixaban is associated with a significantly lower risk of major bleeding compared to rivaroxaban for treatment of VTE. Given the limitations of the existing evidence, further interventional studies comparing the two drugs are needed.

Management and Evolution after VTE Recurrence and/or Bleeding in Cancer Patients Receiving Anticoagulant Therapy for VTE: A Nationwide Cohort Study in France

CONCLUSION Until recently, the standard of care for treatment of venous thromboembolism ( VTE) in cancer patients was low molecular weight heparins (LMWH). Despite anticoagulation therapy (AC), patients remain at high risk of treatment failure (VTE recurrence and/or bleeding). To determine the characteristics, management and the course of treatment after experiencing a recurrent VTE and/or bleeding event in VTE cancer patients receiving LMWH. A nationwide retrospective cohort study of all adult patients (identified via the French national health data system: SNDS) with VTE and active cancer prescribed LMWH from 2013 to 2018. Of 31,771 patients administered LMWH, 1,256 patients (mean age 64.1 years) experienced a recurrent VTE (median time to the first recurrent VTE event: 1.2 months) and 1,129 patients (mean age 67.5 years) experienced a bleeding event leading to hospitalization (median time to the first bleeding event: 1.5 months) during the first six months, and among them 46.7% and 40.9% patients experienced the event within the first month. The proportion of patients with recurrent VTE and bleeding varied according to cancer sites (7.3%, 6.5% and 5.1% for recurrent VTE and 5.0%, 6.1% and 4.1% for bleeding, respectively in lung, colorectal and breast cancer) (Figure 1). The management of patients with recurrent VTE consisted of a switch to another AC treatment in 370 patients, in whom 262 switched to an oral AC (179 to a DOAC and 83 to a VKA), the remaining continuing LMWH. The management of patients with bleeding consisted of a switch to another AC treatment in 159 patients. Among the 159 switched patients, 94 switched to an oral AC (73 to a DOAC and 21 to a VKA), <10 stopped AC (Figure 2). Our results indicate that recurrent VTE and bleeding events lead to a heterogenous switch of AC therapy. Further research is needed to optimize secondary AC management in VTE cancer patients. This study was sponsored by Pfizer and Bristol Myers Squibb Keywords : venous thromboembolism; cancer; anticoagulants; bleeding; low molecular weight heparin; treatment pattern

Risk Factors for Thrombosis in Pregnant People with Sickle Cell Disease: A Multinational Study.

Background People with sickle cell disease (SCD) have exceptionally high rates of maternal morbidity, including increased risk for venous thromboembolic events (VTE). Data from the National Inpatient Sample shows that VTE risk in hospitalized Black pregnant people with SCD is 14 times that of unaffected Black and non-Black pregnant people. 1 There is little disease-specific data to inform anticoagulation (AC) use during pregnancy. 2 The purpose of this study is to describe VTE events in a SCD pregnancy cohort and to identify risk factors for VTE during pregnancy and compare maternal-fetal outcomes for subjects with or without VTE in pregnancy. Methods The Mount Sinai Hospital (MSH) Research Ethics Board and The Johns Hopkins Hospital (JHH) Institutional Review Board approved this retrospective study of pregnant people with SCD of ≥ 20 weeks gestation cared for at MSH, Toronto (1990-2017) or JHH (2000-2021). At MSH and JHH, all pregnant people with SCD and VTE history are prescribed antenatal prophylactic LMWH and for 6-weeks postpartum. At MSH, but not JHH, all receive AC prophylaxis for 6-weeks postpartum. At both centers, hospitalized pregnant people receive prophylactic AC. We stratified subjects by VTE occurrence during pregnancy. First, we described the cohort with VTE during pregnancy, including subject characteristics, VTE recurrence and pregnancy outcomes. Second, we compared cases with a first pregnancy with VTE to controls without VTE. We excluded repeat pregnancies in both groups. We compared cases and controls by SCD characteristics, medication use before pregnancy, and pregnancy outcomes. Painful events were defined as pain requiring acute care or hospital admission. Chronic transfusion therapy (CTT) was defined as pregnancies treated with scheduled, prophylactic transfusion; opioid use was defined as receiving an outpatient opioid prescription during pregnancy. We used the Chi-squared test for categorical variables and Wilcoxon signed-rank tests for continuous variables. A p-value of <0.05 was considered significant. Results There were 290 singleton pregnancies in 199 subjects. Half of the pregnancies were first pregnancies (142/290), with fewer second (51/290), third (2/290), fourth (3/290) or fifth (1/290) pregnancies. The cohort comprised of 58% subjects with HbSS/HbSβ 0, while 42% had HbSC/HbSβ+ genotype (Table 1). VTE occurred in 7% of pregnancies (20/290) including deep vein thrombosis (DVT, N=9), pulmonary embolism (PE, N=8), DVT+PE (N=3). Median age was 27 years (IQR 23,30). Before pregnancy, most VTE subjects received hydroxyurea (N=10). During pregnancy, six received CTT. Fourteen subjects had VTE in a single pregnancy; three had VTE recurrence in subsequent pregnancies. All three had HbSS/HbSβ 0. Two subjects had VTE history outside of pregnancy. One had DVT in two consecutive pregnancies and was prescribed AC in both pregnancies due to history of VTE. VTE occurred in first (N=4), second (N=8), third (N=4), fourth (N=1) and fifth (N=4) pregnancies. Most VTE occurred at JHH (11 JHH vs 6 MSH, p=0.008). To investigate SCD-specific risk factors for VTE in pregnancy, we compared characteristics in VTE subjects (N=17) to no-VTE subjects (N=182) by first study pregnancy with an event or first study pregnancy while enrolled in the study. VTE was associated with markers of disease severity including history of VTE before pregnancy (6/17 VTE vs 8/182 no-VTE, p<0.001), ACS during pregnancy (7/17 VTE vs 19/182 no-VTE, p<0.001), painful events requiring acute care during pregnancy (16/17 VTE vs 119/182 no-VTE, p=0.015) and hydroxyurea use before pregnancy (10/17 VTE vs 35/184 no-VTE, p<0.001). There was no difference in age or genotype. VTE was associated with earlier delivery and c-section delivery (Table 1). Conclusion In this study, 7% of cohort pregnancies had VTE. This rate exceeds reports from administrative datasets. 1 This may be due to the acuity of patients cared for at our centers and/or reflect undercounting of VTE in administrative datasets. In pregnant people with SCD, VTE is associated with VTE history, intrapartum painful events and ACS. Interventions to reduce acute events in pregnancy may help reduce VTE risk. While AC can be beneficial in preventing thrombotic events, careful assessment is essential to manage bleeding risks. Prospective data is needed to define the subpopulation of pregnant SCD patients who would benefit from AC prophylaxis antenatally.

Risk of Recurrent Venous Thromboembolism in Patients with Acute Isolated Subsegmental Pulmonary Embolism - a Single Center Chart Review

Introduction: The incidence of pulmonary embolism (PE) has been increasing, but its case-fatality rate is decreasing over time, suggesting overdiagnosis, a lesser severity of the illness and/or improvements in treatment strategies. Approximately 10-14% of all diagnosed PE are isolated to the subsegmental vessels. The risk of recurrent venous thromboembolism (VTE) in patients with an acute subsegmental pulmonary embolism (SSPE), managed with or without anticoagulant therapy, remains poorly understood. Methods and analysis: This is an observational, retrospective cohort study of adult patients diagnosed with an acute isolated SSPE (single or multiple) at The Ottawa Hospital, Ontario, Canada, from June 01, 2019, to August 31, 2022. Data on diagnosis and follow-up were collected through a retrospective review of the medical records. Among inclusion criteria, no selection was made on provoking factors or on presence/absence of symptoms at presentation. We excluded those patients with concomitant diagnosis of deep vein thrombosis (DVT) who were started on anticoagulation and those who had an indication for long-term anticoagulation at the time of SSPE diagnosis (e.g. atrial fibrillation). The primary outcome was recurrent VTE events other than SSPE, occurring after the diagnosis among patients managed without anticoagulation, and after treatment initiation among those treated with anticoagulation. Results: Overall, 120 patients with a diagnosis of acute SSPE were included in the analysis. The mean age of the participants was 59 +/- 3 years, 47% were women, the mean body weight was 76 +/- 4 kg, and 35% of them had active cancer. Seventy-nine patients (66%) were treated with anticoagulation, whereas 41 patients (34%) were not. The most frequent treatment was direct oral anticoagulant, being used in 64/79 patients (81%), whereas 15/79 patients (19%) received low molecular weight heparin. Most patients were treated for 3-6 months. Twenty-one (28%) of treated patients continued long-term anticoagulation for secondary prevention. Individuals with active cancer at time of SSPE diagnosis were 32/79 (41%) and 10/41 (24%), respectively among treated and not treated patients. Overall, duration of follow-up was 452 +/- 77 days; 7 patients were lost to follow-up. Recurrent VTE events occurred in 7/113 (6.2%) patients: 5/75 (6.7%, 95% CI 2.2 to 14.9) of them were diagnosed in the treatment group (2 occurred while on anticoagulation and 3 after discontinuation of treatment) and the other 2/38 (5.3%, 95% CI 0.6 to 17.8) were detected among patients managed without anticoagulation. Recurrences were mostly represented by more proximal PEs (5 patients), one patient had an upper extremity DVT and the other one was diagnosed with both DVT and proximal PE. Conclusions: In our retrospective cohort study, most patients diagnosed with an acute SSPE received anticoagulation. The prevalence of recurrent thromboembolic events detected over more than a year follow-up was relatively high, with 6.7% and 5.3%, respectively, among patients treated with anticoagulation and those managed without anticoagulation. Further data are needed to better understand the natural history of this thrombotic complication and to identify the right patients who would benefit from anticoagulation.

The Choice of Anticoagulant at First Recurrence Does Not Alter the Risk for the Second Recurrence

Introduction : Venous thromboembolism (VTE), encompassing deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major public health hazard, with up to 30-50% of patients with unprovoked VTE experiencing a recurrent VTE event. These recurrent VTE events are associated with significant morbidity and mortality. However, transition strategies to second-line anticoagulation regimens following the first recurrence on anticoagulation have not been well studied. We sought to examine whether rates of the second VTE recurrence were different in those patients who changed their anticoagulation regimen from those who did not . Methods: With an IRB approval for the study, we created a database of all patients 18 years and older diagnosed with the first recurrent VTE at a large tertiary academic hospital between January 1, 2010, and December 31, 2019. The collected data was de-identified and compiled in a secure, standardized institutional database. We assessed the anticoagulation status at the time of and immediately following the first VTE recurrence, and identified patients who were switched to a different anticoagulant regimen. We used Fisher's exact test to evaluate proportions. Statistical significance was set at p<0.05. Results:We identified 138 patients with the first VTE recurrence. Of these patients, 114 (83%) developed DVT, 7 (5%) PE, and 17 (12%) both DVT and PE. Mean age was 63 years at the time of first VTE; 70 (51%) were female. Racial/ethnic representation was 84 (61%) White, 46 (33%) Black, and 133 (96%) non-Hispanic. The majority of patients had cardiovascular risk factors, including hypertension 80 (58%), hyperlipidemia 44 (32%), ordiabetes 40 (29%). Among 138 patients, 32 (23%) had active cancer, May-Thurner syndrome or inferior vena cava (IVC) atresia were reported in 13 (9%) of cases, and 21 (17%) underwent IVC filter placement at the time of the first VTE recurrence. The median follow-up time after diagnosis of a second VTE was 5 years. Following the first VTE recurrence, 19 (14%) of patients switched to a different anticoagulant agent, 7 (5%) had the dose of the anticoagulant adjusted, 1 (0.7%) was given a different INR target, and one had a change in the frequency of administration. The second VTE occurred in 49 (46%) patients who remained on the same anticoagulation regimen and in 3 (16%) who had the agent changed, in 5 who had dose of anticoagulant changed, in 1 (100%) each who had frequency or INR target changed. The association between unprovoked first VTE and the development of the second VTE was not significant (p= 0.85, Fisher's exact test). 49 (36%) of patients had at least one bleeding episode requiring the interruption of anticoagulation or hospitalization. Of those, 43 (88%) occurred while on an anticoagulant. Conclusion: The choice of an anticoagulant regimen after the first VTE recurrence does not impact the rate of the second recurrence.

Management of Catheter-Related Upper Extremity Deep Vein Thrombosis in Patients with Cancer: A Systematic Review and Meta-Analysis

Background: Patients with cancer commonly require a central venous catheter (CVC) for delivery of cancer therapies and/or supportive care. The presence of a CVC is associated with an increased risk of venous thromboembolism (VTE). Despite the frequent occurrence, the optimal anticoagulation management and outcomes for patients with cancer and catheter-related upper extremity deep vein thrombosis (DVT) are unclear. Objective: We performed a systematic review and meta-analysis to evaluate the rates of recurrent VTE and bleeding complications in patients with cancer and catheter-related upper extremity DVT. Methods: We searched MEDLINE, Embase, Scopus, and CENTRAL (Cochrane) from inception to June 2, 2023. We aimed to include randomized controlled trials (RCTs) (if any), prospective and retrospective cohort studies, and case-control studies (including ≥ 10 patients) evaluating adult patients with cancer and catheter-related upper extremity DVT. The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding as defined by individual studies. Secondary outcomes included clinically relevant non-major bleeding, total bleeding events, and all-cause mortality. By using R software (version 4.0.3), the incidence rates (with 95% confidence interval [CI]) of recurrent VTE and bleeding outcomes at different time points were pooled using random effects model. Results: After screening 4,264 records, we included 29 studies (N=2,848 patients) in the systematic review. There were no RCTs, 5 prospective cohort studies (including 260 patients), and 24 retrospective cohort studies. Most studies had modest sample size (N<100). Overall from 24 studies with reported tumor types, the most common malignancy was hematological malignancy (50.4%), followed by gastrointestinal (13.6%), breast (10.2%), and lung (5.5%) cancers. The median or mean follow-up duration varied widely from 1 to 20 months. Duration of anticoagulation also varied considerably with median or mean duration of 20 days to 6 months. The main long-term anticoagulant used was low-molecular-weight heparin (58.1%), followed by direct oral anticoagulants (24.3%). Only two studies (N=87 patients) specifically reported the management and associated outcomes after catheter removal. Thirteen studies (N=1105 patients) reported a 3-month recurrent VTE rate, with the pooled rate of 1% (95% CI 0-3%, I 2 = 0%) (Figure 1). Nine studies (N=811 patients) reported a 3-month major bleeding rate, with the pooled rate of 2% (95% CI 1-5%, I 2 = 0%) (Figure 2). We were unable to pool event rates beyond 3 months given high degree of heterogeneity in the follow-up duration, bleeding definition, and duration of anticoagulation. Conclusions: Our systematic review and meta-analysis demonstrated relatively low rates of recurrent VTE and major bleeding events within the first 3 months in patients with cancer and catheter-related upper extremity DVT. However, there was significant heterogeneity in the management and reporting after 3 months, and available data are poor to guide treatment strategies and duration of anticoagulation. The optimal management after catheter removal was also unclear. Future large prospective studies are needed.

Abstract 14480: Safety and Efficacy of Direct Oral Anticoagulants vs Low Molecular Weight Heparin for Treatment of Venous Thromboembolism in Patients With Cancer

Introduction: Direct oral anticoagulants (DOACs) have been studied for treatment of venous thromboembolism (VTE) in patients with cancer. However, the trials have shown conflicting results when compared with low molecular weight heparin (LMWH). Therefore, we aimed to conduct an updated meta-analysis of the available studies. Methods: Randomized controlled trials (RCTs) comparing DOAC vs LMWH for VTE treatment in cancer patients were searched from multiple online databases. The primary endpoints of interest were recurrent VTE, major bleeding, clinically relevant non major bleeding (CRNB) and mortality at the longest available follow up. A random-effects model was used to estimate risk ratios (RR) with 95% confidence intervals (CI). Results: Six RCTs, with a total of 3,703 patients - 1,855 in the DOAC group and 1,848 in the LMWH group were included. Around 49% of patients were men and the mean age was 66 years. The follow up duration varied from 3 to 24 months. Patients treated with DOAC, when compared with the LMWH group, had lower risk of recurrent VTE (RR 0.66, 95% CI 0.52-0.83, p = 0.0005) (Figure 1), but a higher risk of CRNB (RR 1.63, 95% CI 1.19-2.23, p = 0.002). No significant differences were found between the two groups with regards to major bleeding (RR 1.19, 95% CI 0.82-1.71, p = 0.36) (Figure 2) or overall mortality (RR 1.02, 95% CI 0.90-1.14, p = 0.78). Conclusions: For treatment of VTE, DOACs as compared with LMWH are associated with significant reduction of recurrent VTE events but with a higher risk of CRNB.

The prevalence of relevant drug-drug interactions and associated clinical outcomes in patients with cancer-associated thrombosis on concurrent anticoagulation and anticancer or supportive care therapies

BackgroundA main concern in the management of patients with cancer-associated thrombosis (CAT) is drug-drug interactions (DDIs) between anticoagulants and anticancer therapies. Their clinical implications remain unclear. MethodsTo quantify the prevalence of DDIs and risks of recurrent venous thromboembolism (VTE) and bleeding events in patients with CAT on anticoagulation, we conducted a retrospective cohort study in patients with CAT on concurrent anticoagulants and anticancer and/or supportive care therapies. All patients were followed for 6 months from CAT diagnosis or until death (whichever occurred first). The primary outcome was the percentage of patients with anticoagulant DDIs classified as risk C, D, or X in Lexicomp® at any time during the 6 months. Secondary outcomes included recurrent VTE and clinically relevant bleeding events. We calculated the 6-month cumulative incidence of outcomes with 95 % confidence interval (CI) and compared those with and without DDIs, considering death as a competing risk. ResultsAmong 267 patients included, 111 (41.6 %) had DDIs with anticoagulants at any time during the study. Those on DOACs at any time had more DDIs compared to LMWH (50.9 % vs 19.3 %, p < 0.0001). The 6-month incidence was 8.2 % (95 % CI 5.3–11.9) for recurrent VTE and 6.7 % (95 % CI 4.2–10.2) for clinically relevant bleeding, with no significant differences between groups with or without DDIs. ConclusionsThere are high incidences of DDIs in patients with CAT on anticoagulants, more with DOACs. DDIs classified as risk C, D, or X by Lexicomp® were not associated with recurrent VTE or bleeding events in our cohort.

Safety and efficacy of direct oral anticoagulants in patients with chronic thromboembolic pulmonary hypertension

IntroductionChronic thromboembolic pulmonary hypertension (CTEPH) remains an underdiagnosed disease. Anticoagulation is essential in its therapy to prevent recurrent venous thromboembolism (VTE). According to some international guidelines, vitamin K antagonists (VKA) remain the gold standard. Nevertheless, direct oral anticoagulants (DOAC) are widely used, partly because of numerous advantages. The objective of this study was to determine if DOAC is an effective and safe alternative to VKA in CTEPH patients. Materials and methodsA retrospective observational study was conducted between 2001 and 2021 in a CTEPH Clinic of a tertiary care hospital. We recorded demographic characteristics, anticoagulant therapies and pulmonary hypertension treatments received. Safety outcomes were bleeding events and deaths while efficacy outcomes were recurrent VTE events. ResultsAmong the study population (N = 205), the distribution of anticoagulant used transitioned from majority on VKA to majority on DOAC. In 2020, 23 (19 %) were on VKA and 97 (78 %) on DOAC. Among 11 VTE events occurring during follow-up, 7 were in the VKA group (1.10 %/person-year) and 1 in the DOAC group (0.32 %/person-year). Rates of VTE recurrence were not significantly different in those treated with DOAC compared to VKA (P = 0.21). Total bleeding rate on VKA (2.52 %/person-year) and DOAC (2.52 %/person-year) were the same (P = 1.00). Among 27 patients who died, no deaths occurred as a consequence of bleeding or VTE events. ConclusionBleeding and VTE events were not higher in CTEPH patients receiving DOAC compared to VKA which adds confidence to considering DOAC as an effective and safe alternative for long term anticoagulation in CTEPH patients.

Indefinite Anticoagulant Therapy for First Unprovoked Venous Thromboembolism : A Cost-Effectiveness Study.

Clinical practice guidelines recommend indefinite anticoagulation for a first unprovoked venous thromboembolism (VTE). To estimate the benefit-harm tradeoffs of indefinite anticoagulation in patients with a first unprovoked VTE. Markov modeling study. Systematic reviews and meta-analyses for the long-term risks and case-fatality rates of recurrent VTE and major bleeding. Published literature for costs, quality of life, and other clinical events. Patients with a first unprovoked VTE who have completed 3 to 6 months of initial anticoagulant treatment. Lifetime. Canadian health care public payer. Indefinite anticoagulation with direct oral anticoagulants. Recurrent VTE events, major bleeding events, costs in 2022 Canadian dollars (CAD), and quality-adjusted life-years (QALYs). When compared with discontinuing anticoagulation after initial treatment in a hypothetical cohort of 1000 patients aged 55 years, indefinite anticoagulation prevented 368 recurrent VTE events, which included 14 fatal pulmonary emboli, but induced an additional 114 major bleeding events, which included 30 intracranial hemorrhages and 11 deaths from bleeding. Indefinite anticoagulation cost CAD $16 014 more per person and did not increase QALYs (-0.075 per person). Model results were most sensitive to the case-fatality rate of major bleeding and the annual risk for major bleeding during extended anticoagulation. The model assumed that risks for recurrent VTE and major bleeding measured in clinical trials at 1 year remained constant during extended anticoagulation. Clinicians should use shared decision making to incorporate individual patient preferences and values when considering treatment duration for unprovoked VTE. Canadian Institutes of Health Research.

Recurrent, life-threatening PE in the setting of popliteal vein aneurysm in pregnancy: a case report

BackgroundPopliteal vein aneurysms (PVA) are a rare clinical entity with unknown etiology that pose a significant risk for venous thromboembolic events (VTE). The current literature supports anticoagulation and operative management. There are few case reports of PVA in pregnancy. We present a unique case of a pregnant patient with recurrent pulmonary embolism (PE) in the setting of PVA with intra-aneurysmal thrombosis who ultimately underwent surgical excision.Case presentationA previously healthy 34-year-old G2P1 at 30 weeks gestation presented to the emergency department with shortness of breath and chest pain. She was diagnosed with PE and subsequently required intensive care unit (ICU) admission and thrombolysis for a massive PE. While on a therapeutic dose of tinzaparin she had recurrence of PE in the post-partum period. She was treated with supratherapeutic tinzaparin and subsequently transitioned to warfarin. She was found to have a PVA and ultimately underwent successful PVA ligation. She remains on anticoagulation for secondary prevention of VTE.ConclusionsPVA are a rare but potentially fatal source of VTE. Patients most commonly present with symptoms of PE. The risk of VTE is elevated in the pro-thrombotic states of pregnancy and the post-partum period due to both physiologic and anatomical changes. The recommended management of PVA with PE is anticoagulation and surgical resection of the aneurysm, however this can be complicated in the setting of pregnancy. We demonstrated that pregnant patients with PVA can be temporized with medical management to avoid surgical intervention during pregnancy, but require close symptom monitoring and serial imaging to reassess the PVA, with high index of suspicion for recurrent VTE. Ultimately, patients with PVA and PE should undergo surgical resection to reduce the risk of recurrence and long-term complications. The ideal duration of post-operative anticoagulation remains unclear, and should likely be decided on based on risks, benefits, values, and shared decision making with the patient and their care provider.

Comparative effectiveness and safety of direct oral anticoagulants versus warfarin among patients with recurrent venous thromboembolism.

The comparative effectiveness and safety of oral anticoagulant therapies to prevent a second recurrent venous thromboembolism (VTE) remains undetermined. We aimed to compare the benefits and harms of direct oral anticoagulant (DOAC) and warfarin therapies in preventing second recurrent VTE and major bleeding events among patients with a recurrent VTE episode following anticoagulation therapy for incident VTE. A retrospective cohort analysis of two large national insurance claims databases was conducted for patients with two episodes of VTE. Cox proportional hazards models were used after inverse probability treatment weighting to compare risks of second recurrent VTE and major bleeding events. Compared with warfarin, DOAC therapy was associated with significantly decreased risk of second recurrent VTE with no significant difference in risk of major bleeding events. Our findings suggest that, compared with warfarin, DOACs may reduce risk of second VTE recurrence among patients who have experienced one recurrence.