Lower Risk Of Recurrent Venous Thromboembolism 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.

Non-Vitamin K Antagonist Oral Anticoagulants versus Low Molecular Weight Heparin for Cancer-Related Venous Thromboembolic Events: Individual Patient Data Meta-Analysis.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in cancer patients. Low molecular weight heparin (LMWH) has been the standard of care but new guidelines have approved the use of non-vitamin K antagonist oral anticoagulants (NOAC). By conducting an individual patient data (IPD) meta-analysis of randomised controlled trials (RCTs) comparing the outcomes of NOAC versus LMWH in cancer patients, we aim to determine an ideal strategy for the prophylaxis of VTE and prevention of VTE recurrence. Three databases were searched from inception until 19 October 2022. IPD was reconstructed from Kaplan-Meier curves. Shared frailty, stratified Cox and Royston-Parmar models were fit to compare the outcomes of venous thromboembolism recurrence and major bleeding. For studies without Kaplan-Meier curves, aggregate data meta-analysis was conducted using random-effects models. Eleven RCTs involving 4844 patients were included. Aggregate data meta-analysis showed that administering NOACs led to a significantly lower risk of recurrent VTE (RR = 0.65; 95%CI: 0.50-0.84) and deep vein thrombosis (DVT) (RR = 0.60; 95%CI: 0.40-0.90). In the IPD meta-analysis, NOAC when compared with LMWH has an HR of 0.65 (95%CI: 0.49-0.86) for VTE recurrence. Stratified Cox and Royston-Parmar models demonstrated similar results. In reducing risks of recurrent VTE and DVT among cancer patients, NOACs are superior to LMWHs without increased major bleeding.

Venous thromboembolism, chronic liver disease and anticoagulant choice: effectiveness and safety of direct oral anticoagulants versus warfarin

BackgroundLittle to no data exist to guide treatment decision in patients with venous thromboembolism (VTE) and chronic liver disease. ObjectivesTo assess the effectiveness and safety of direct oral anticoagulants (DOACs)—individually and as a class—vs warfarin and between 2 DOACs in patients with acute VTE and chronic liver disease. MethodsWe conducted a retrospective, US claims–based, propensity score–matched cohort study in adults with acute VTE and chronic liver disease who had newly initiated oral anticoagulants between 2011 and 2017. The primary outcome was a composite of hospitalization for recurrent VTE and hospitalization for major bleeding. ResultsThe cohorts included 2361 DOAC-warfarin, 895 apixaban-warfarin, 2161 rivaroxaban-warfarin, and 895 apixaban-rivaroxaban matched pairs. Lower risk of the primary outcome was seen with DOACs (hazard ratio [HR], 0.72; 95% CI, 0.61-0.85), apixaban (HR, 0.48; 95% CI, 0.35-0.66) or rivaroxaban (HR, 0.73; 95% CI, 0.61-0.88) vs warfarin but not apixaban-rivaroxaban (HR, 0.68; 95% CI, 0.43-1.08). The HRs of hospitalization for major bleeding were 0.69 (95% CI, 0.57-0.84) for DOAC-warfarin, 0.43 (95% CI, 0.30-0.63) for apixaban-warfarin, 0.72 (95% CI, 0.58-0.89) for rivaroxaban-warfarin, and 0.60 (95% CI, 0.35-1.06) for apixaban-rivaroxaban. Recurrent VTE risk was lower with apixaban (HR, 0.47; 95% CI, 0.26-0.86), but not DOACs (HR, 0.81; 95% CI, 0.59-1.12) or rivaroxaban vs warfarin (HR, 0.81; 95% CI, 0.57-1.14) or apixaban-rivaroxaban (HR, 0.92; 95% CI, 0.42-2.02). ConclusionWhile the magnitude of clinical benefit varied across individual DOACs, in adults with acute VTE and chronic liver disease, oral factor Xa inhibitors (as a class or individually) were associated with lower risk of recurrent VTE and major bleeding.

The Efficacy and Safely of Anticoagulation for the Management of Gonadal Vein Thrombosis

Background Gonadal vein thrombosis (GVT) is an uncommon condition that has been associated with different risk factors (e.g., post-partum period, cancer, recent pelvic surgery, etc.). The optimal management of GVT remains unclear. Anticoagulation therapy may help to mitigate the risk of thrombosis extension and recurrent venous thromboembolism (VTE) but may also be associated with bleeding complications.We sought to assess the efficacy and safety of anticoagulation therapy in patients with GVT. Methods A systematic search of MEDLINE, EMBASE and PubMed for randomized controlled trials and observational studies was performed . Studies with patients presenting with GVT defined as ovarian vein thrombosis or testicular vein thrombosis and reporting at least one of the desired outcomes were included in the analysis.The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding episode. Secondary outcomes included clinically relevant non-major bleeding and overall mortality. Incidence rates of the outcomes were pooled using the random effects model and expressed as event per 100 patient-years with its associated 95% confidence intervals (CI) using R software. Results The search strategy identified 7084 article records. A total of 13 observational studies (1039 patients) with GVT met the inclusion criteria and were included in the analysis. Only one study reported the incidence of testicular vein thrombosis. Hence, 96% of the total patient population were females with ovarian vein thrombosis. Overall, the incidence rate per 100 patient-years for recurrent VTE was 3.60 (95% CI: 2.12-6.13; I-square 75%; Figure 1). A large majority of studies did not report if recurrent events occurred during or following discontinuation of anticoagulation. Similarly, most studies did not report on major or clinically relevant non-major bleeding events, or overall mortality preventing the possibility of conducting pooled analyses for these outcomes. Conclusion GVT seems to be associated with a relatively low risk of recurrent VTE. However, it remains unclear if anticoagulant therapy is associated with a favorable risk/benefit ratio. Future studies (e.g., registries, population-based studies) are needed to investigate the efficacy of anticoagulant and whether it outweighs the risk of bleeding in this patient population.

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.

Abstract 17843: Direct Oral Anticoagulants versus Low Molecular Weight Heparin for Venous Thromboembolism in Cancer Patients: An Updated Systematic Review and Meta-Analysis

Introduction: Patients with cancer have an increased risk of venous thromboembolism (VTE). We aim to evaluate the risk of recurrent VTE and major bleeding in patients with cancer when started on DOACs versus low molecular weight heparin (LMWH). Methods: We conducted a systematic literature search according to PRISMA guidelines to identify studies using the terms: “venous thromboembolism,” “low molecular weight heparin,” and “direct oral anticoagulants.” After the screening, We extracted the data until May 2023 in a data extraction sheet. Our inclusion criteria were: adult patients, and cancer patients, who were on DOACs or LMWH for VTE or atrial fibrillation. We used a variance-weighted random-effects model to analyze data on DOACs vs. LMWH, estimating event rates and odds ratios while assessing heterogeneity. Data were analyzed using the ‘meta’ package in R. Results: Our analysis included 16 studies (n= 12216 patients). Cancer patients on DOACs significantly reduced the risk of recurrent VTEs compared to LMWHs OR 0.69 (95% CI: 0.56- 0.86, I 2:23% ). However, for major bleeding and clinically relevant non-major bleeding, although the statistical significance was not reached, a consistent trend favoring DOACs was observed (OR = 0.92, 95% CI: 0.65-1.30) and OR=1.19 (0.90-1.59) respectively. (Figure1) Conclusions: Among cancer patients, DOACs are associated with a significantly lower risk of recurrent VTEs than LMWHs. Although the statistical significance was not reached for major bleeding and clinically relevant non-major bleeding, there was a trend favoring DOACs over VKA. Increased recruitment of cancer patients in clinical trials is needed to provide us with updated data to refine treatment strategies.

Efficacy and Safety of Apixaban versus Dalteparin as a Treatment for Cancer-Associated Venous Thromboembolism: A Systematic Review and Meta-Analysis.

Background and Objectives: Venous thromboembolism (VTE) is common in cancer patients. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs), such as dalteparin and apixaban, have demonstrated efficacy and safety. However, more comparative research of these drugs is still needed. This study aimed to synthesize evidence on the efficacy of apixaban compared to dalteparin in reducing recurrent VTE, major bleeding, and clinically relevant non-major bleeding associated with cancer. Materials and Methods: We systematically searched the PubMed, Scopus, Web of Science, Embase, Cochrane Library, and ClinicalTrials databases up to 5 January 2023, for randomized controlled trials comparing apixaban versus dalteparin as treatment for cancer-associated VTE. Five studies were included. Effects according to meta-analyses were reported as relative risks (RRs) and their 95% confidence intervals (CIs). Results: It was found that 33 of 734 (4.5%) patients treated with apixaban and 56 of 767 (7.3%) with dalteparin had recurrent VTE as the efficacy outcome (RR 0.49, 95% CI 0.15-1.58, I2 38%). Major bleeding occurred in 25 of 734 patients treated with apixaban (3.4%) and 27 of 767 with dalteparin (3.5%) (RR 1.29, 95% CI 0.31-5.27, I2 59%). Likewise, clinically relevant non-major bleeding occurred in 64 of 734 patients treated with apixaban (8.7%) and 46 of 767 (5.9%) with dalteparin (RR 1.52, 95% CI 1.05-2.19, I2 0%). Conclusions: Apixaban showed a lower risk of recurrent VTE than dalteparin in patients with cancer-associated VTE, but without statistical significance. No statistical significance was observed in clinically relevant major or non-major bleeding.

Serial D-dimers after anticoagulant cessation in unprovoked venous thromboembolism: Data from the REVERSE cohort study

IntroductionWhile several risk stratification tools have been developed to predict the risk of recurrence in patients with an unprovoked venous thromboembolism (VTE), only 1 in 4 patients are categorized as low-risk. Rather than a one-time measure, serial D-dimer assessment holds promise to enhance the prediction of VTE recurrence after oral anticoagulant (OAC) cessation. MethodsUsing the REVERSE cohort, we compared VTE recurrence among patients with normal D-dimer levels (<490 ng/mL among males under age 70, <500 ng/mL in others) at OAC cessation and 1-month follow-up, to those with an elevated D-dimer level at either timepoint. We also evaluated VTE recurrence based on absolute increase in D-dimer levels between the two timepoints (e.g., ∆D-dimer) according to quartiles. ResultsAmong 214 patients with serial D-dimer levels measured at OAC cessation and 1-month follow-up, an elevated D-dimer level at either timepoint was associated with a numerically higher risk of recurrent VTE than patients with normal D-dimer levels at both timepoints (6.9 % vs. 4.2 % per year, hazard ratio 1.6; 95 % CI 0.9–2.7). Among women with <2 HERDOO2 criteria, a normal D-dimer level at both timepoints predicted a very low risk of recurrent VTE during follow-up (0.8 % per year, 95 % CI 0.1–2.8). Irrespective of baseline value, recurrent VTE risk was only 3 % per year (95 % CI 1.4–5.6) among patients in the lowest ∆D-dimer quartile. ConclusionSerial normal D-dimer levels have the potential to identify patients at a low risk of recurrent VTE. In addition, ∆D-dimer, irrespective of its elevation above cutoff threshold, may predict recurrent VTE.

Clinical Outcomes of Direct Oral Anticoagulants vs Warfarin for Extended Treatment of Venous Thromboembolism

Extending the duration of oral anticoagulation for venous thromboembolism (VTE) beyond the initial 3 to 6 months of treatment is often recommended, but it is not clear whether clinical outcomes differ when using direct oral anticoagulants (DOACs) or warfarin. To compare rates of recurrent VTE, hospitalizations for hemorrhage, and all-cause death among adults prescribed DOACs or warfarin whose anticoagulant treatment was extended beyond 6 months after acute VTE. This cohort study was conducted in 2 integrated health care delivery systems in California with adults aged 18 years or older who received a diagnosis of incident VTE between 2010 and 2018 and completed at least 6 months of oral anticoagulant treatment with DOACs or warfarin. Patients were followed from the end of the initial 6-month treatment period until discontinuation of anticoagulation, occurrence of an outcome event, health plan disenrollment, or end of the study follow-up period (December 31, 2019). Data were obtained from the Kaiser Permanente Virtual Data Warehouse and electronic health records. Data analysis was conducted from March 2022 to January 2023. Dispensed prescriptions of DOACs or warfarin after a 6-month initial treatment for VTE. The primary outcomes were rates per 100 person-years of recurrent VTE, hospitalizations for hemorrhage, and all-cause death. Comparison of DOAC and warfarin outcomes were performed using multivariable Cox proportional hazards regression. A total of 18 495 patients (5477 [29.6%] aged ≥75 years; 8973 women [48.5%]) with VTE who were treated with at least 6 months of anticoagulation were identified, of whom 2134 (11.5%) were receiving DOAC therapy and 16 361 (88.5%) were receiving warfarin therapy. Unadjusted event rates were lower for patients receiving DOAC therapy than warfarin therapy for recurrent VTE (event rate per 100 person-years, 2.92 [95% CI, 2.29-3.54] vs 4.14 [95% CI, 3.90-4.38]), hospitalizations for hemorrhage (event rate per 100 person-years, 1.02 [95% CI, 0.66-1.39] vs 1.81 [95% CI, 1.66-1.97]), and all-cause death (event rate per 100 person-years, 3.79 [95% CI, 3.09-4.49] vs 5.40 [95% CI, 5.13-5.66]). After multivariable adjustment, DOAC treatment was associated with a lower risk of recurrent VTE (adjusted hazard ratio [aHR], 0.66; 95% CI, 0.52-0.82). For patients prescribed DOAC treatment, the risks of hospitalization for hemorrhage (aHR, 0.79; 95% CI, 0.54-1.17) and all-cause death (aHR, 0.96; 95% CI, 0.78-1.19) were not significantly different than those for patients prescribed warfarin treatment. In this cohort study of patients with VTE who continued warfarin or DOAC anticoagulation beyond 6 months, DOAC treatment was associated with a lower risk of recurrent VTE, supporting the use of DOACs for the extended treatment of VTE in terms of clinical outcomes.

Comparative Efficacy of Oral Apixaban and Subcutaneous Low Molecular Weight Heparins in the Treatment of Cancer-Associated Thromboembolism: A Meta-Analysis.

Cancer patients' risk of developing venous thromboembolism (VTE) is four to seven times higher than the general population. Cancer-associated VTE (CA-VTE), is a leading cause of morbidity and mortality in cancer patients. Low Molecular Weight Heparin (LMWH) has historically been the mainstay treatment ofCA-VTE; however, complications such as bleeding and recurrent VTE make it challenging to manage these patients. Recent randomized controlled trials (RCTs) have proven that direct oral anticoagulants (DOACs) are as efficacious as LMWHs in treating CA-VTE. We conducted a systematic review and meta-analysis to ascertain the efficacy and safety of LMWH and Apixaban for the treatment of CA-VTE.A systematic review was conducted using Medline, Embase, and Scopus, databases for all cohort studies, case-control studies, and RCTs in English comparing cancer patients undergoing treatment with Apixaban or LMWH to treat CA-VTE from inception-May 2023. The Review Manager program, version 5.4.1, was used for statistical analysis and the Mantel-Haenszel fixed-effects models to calculate the risk ratio (RR) and 95% confidence intervals (CIs) and the inverse variance approach to get the weighted mean difference for the continuous outcomes. Q-test for heterogeneity was used to examine statistical heterogeneity and an I2 statistics value >50%was defined as significant heterogeneity. A total of four studies were included, and the total number of patients was 1,632 across all studies. The Apixaban group was associated with a statistically significant increase in minor bleeding (RR 1.57; 95% CI (1.12, 2.21); p=0.009; I2=0%), but not for major and total bleeding. The Apixaban group showed a statistically significant lower risk of recurrent VTE when compared to the LMWH group (RR: 0.61; 95% CI (0.41, 0.92); p=0.02; I2 = 7%), and there was no statistically significant difference in terms of mortality between the two groups (RR: 0.89;95% CI (0.73, 1.09); I2=0). Our findings suggest that Apixaban may be a favorable anticoagulant option for managing cancer-associated thromboembolism, as it demonstrated a lower risk of recurrent VTE. The risk of bleeding with DOAC in gastrointestinal cancers warrants further investigation.

Effectiveness and Safety of Apixaban vs Warfarin in Patients with Venous Thromboembolism with Risk Factors for Bleeding or for Recurrences.

Patients at increased risk of bleeding and recurrent VTE who develop venous thromboembolism (VTE) present challenges for clinical management. This study evaluated the effectiveness and safety of apixaban vs warfarin in patients with VTE who have risk factors for bleeding or recurrences. Adult patients with VTE initiating apixaban or warfarin were identified from five claims databases. Stabilized inverse probability treatment weighting (IPTW) was used to balance characteristics between cohorts for the main analysis. Subgroup interaction analyses were conducted to evaluate treatment effects among patients with and without each of the conditions that increased the risk of bleeding (thrombocytopenia and history of bleed) or recurrent VTE (thrombophilia, chronic liver disease, and immune-mediated disorders). A total of 94,333 warfarin and 60,786 apixaban patients with VTE met selection criteria. After IPTW, all patient characteristics were balanced between cohorts. Apixaban (vs warfarin) patients were at lower risk of recurrent VTE (HR [95% confidence interval (CI) 0.72 [0.67-0.78]), major bleeding (MB) (HR [95%CI] 0.70 [0.64-0.76]), and clinically relevant non-major(CRNM) bleeding (HR [95%CI] 0.83 [0.80-0.86]). Subgroup analyses showed generally consistent findings with the overall analysis. For most subgroup analyses, there were no significant interactions between treatment and subgroup strata on VTE, MB and CRNMbleeding. Patients with prescription fills for apixaban had lower risk of recurrent VTE, MB, and CRNM bleeding compared with warfarin patients. Treatment effects of apixaban vs warfarin were generally consistent across subgroups of patients at increased risk of bleeding/recurrences.

Effectiveness and Safety of Nonvitamin K Oral Anticoagulants Rivaroxaban and Apixaban in Patients with Venous Thromboembolism: A Meta-Analysis of Real-World Studies.

Background Rivaroxaban and apixaban are the most widely used nonvitamin K oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE). This meta-analysis evaluates the effectiveness and safety of both NOACs versus standard of care (SoC) in real-world practice. Methods Real-world evidence (RWE) studies were identified through a systematic literature review conducted between January 2012 and July 2020, using Embase, MEDLINE, and the websites of cardiological, hematological, and oncological associations. Eligible RWE studies recruited adult patients with deep vein thrombosis and/or pulmonary embolism and presented a comparison between rivaroxaban and apixaban versus SoC, consisting either of vitamin K antagonists, heparins, or combinations thereof. Hazard ratios (HRs) for the comparison between NOACs and SoC were extracted from the relevant studies or estimated based on the reported binary data. The between-treatment contrasts were reported as HRs with associated 95% confidence intervals. Results A total of 65 RWE studies were identified and considered relevant for the meta-analysis. Compared with SoC, both rivaroxaban and apixaban were associated with reduced risks of recurrent VTE and a lower rate of major bleeding events. Patients treated with rivaroxaban were at a lower risk of all-cause death compared with those receiving SoC (HR = 0.56 [0.39-0.80]), while evidence for apixaban from the identified studies was insufficient to demonstrate a statistically significant change in mortality (HR = 0.66 [0.30-1.47]). Conclusion This analysis indicates that in real-world practice, rivaroxaban and apixaban are associated with a lower risk of recurrent VTE and major bleeding events compared with SoC. Survival benefit in patients treated with rivaroxaban was also observed.

Anticoagulant therapy for splanchnic vein thrombosis: an individual patient data meta-analysis

AbstractRobust evidence on the optimal management of splanchnic vein thrombosis (SVT) is lacking. We conducted an individual-patient meta-analysis to evaluate the effectiveness and safety of anticoagulation for SVT. Medline, Embase, and clincaltrials.gov were searched up to June 2021 for prospective cohorts or randomized clinical trials including patients with SVT. Data from individual datasets were merged, and any discrepancy with published data was resolved by contacting study authors. Three studies of a total of 1635 patients were included. Eighty-five percent of patients received anticoagulation for a median duration of 316 days (range, 1-730 days). Overall, incidence rates for recurrent venous thromboembolism (VTE), major bleeding, and mortality were 5.3 per 100 patient-years (p-y; 95% confidence interval [CI], 5.1-5.5), 4.4 per 100 p-y (95% CI, 4.2-4.6), and 13.0 per 100 p-y (95% CI, 12.4-13.6), respectively. The incidence rates of all outcomes were lower during anticoagulation and higher after treatment discontinuation or when anticoagulation was not administered. In multivariable analysis, anticoagulant treatment appeared to be associated with a lower risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.27-0.64), major bleeding (HR, 0.47; 95% CI, 0.30-0.74), and mortality (HR, 0.23; 95% CI, 0.17-0.31). Results were consistent in patients with cirrhosis, solid cancers, myeloproliferative neoplasms, unprovoked SVT, and SVT associated with transient or persistent nonmalignant risk factors. In patients with SVT, the risk of recurrent VTE and major bleeding is substantial. Anticoagulant treatment is associated with reduced risk of both outcomes.

Anticoagulant treatment for upper extremity deep vein thrombosis: A systematic review and meta‐analysis

BackgroundData on anticoagulant treatment for upper extremity deep vein thrombosis (UEDVT) are largely derived from studies on usual site venous thromboembolism (VTE). ObjectivesThe objective of this meta‐analysis was to evaluate the efficacy and safety of anticoagulant therapy for UEDVT. Patients/MethodsA systematic search of MEDLINE and EMBASE was conducted for studies including patients with UEDVT. Primary outcomes were recurrent VTE and major bleeding. Secondary outcomes included clinically‐relevant non‐major bleeding and all‐cause mortality. Summary estimates with 95% confidence intervals (CIs) were calculated by random‐effect meta‐analysis. ResultsA total of 1473 patients from 11 prospective and nine retrospective studies were included. Sixty percent of patients had an indwelling catheter and 56.1% had cancer. Anticoagulant treatment consisted of direct oral anticoagulants, low molecular weight heparin followed by vitamin K antagonists, and low molecular weight heparin alone in 45.1%, 35.0%, and 19.9% of patients, respectively. During a median follow‐up of 13 months, recurrent VTE occurred in 3% of patients (95% CI: 2–4; 21/1334 patients), major bleeding in 3% (95% CI: 2%–5%; 29/1235 patients), clinically‐relevant non‐major bleeding in 4% (95% CI: 3–6; 40/1075 patients), and all‐cause mortality in 9% (95% CI: 5–15; 108/1084 patients). Rates of these outcomes were not significantly different between patients with or without cancer, patients with or without an indwelling catheter, and among those receiving different anticoagulant treatments. ConclusionsIn patients with UEDVT, anticoagulant treatment is associated with a low risk of recurrent VTE and a nonnegligible risk of major bleeding.

Effectiveness and Safety of Apixaban versus Warfarin in Venous Thromboembolism Patients with Chronic Kidney Disease.

There has been limited evidence reported about the outcomes of oral anticoagulants among patients with venous thromboembolism (VTE) and chronic kidney disease (CKD), especially those with stage V/end-stage renal disease (ESRD). This retrospective cohort analysis of five U.S. claims databases evaluated the risk of recurrent VTE, major bleeding (MB), and clinically relevant nonmajor bleeding (CRNMB) for apixaban versus warfarin among VTE patients diagnosed with CKD, including ESRD. Inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Hazard ratios (HRs) were calculated for recurrent VTE, MB, and CRNMB among patients with CKD who experienced an index VTE. An interaction analysis was conducted to evaluate treatment effects across different stages of CKD. A total of 29,790 VTE patients with CKD were selected for analyses, of whom 10,669 (35.8%) initiated apixaban and 19,121 (64.2%) initiated warfarin. Among IPTW-balanced patient cohorts, the apixaban group had significantly lower risk of recurrent VTE (HR: 0.78; 95% confidence interval [CI]: 0.66–0.92), MB (HR: 0.76; 95% CI: 0.65–0.88), and CRNMB (HR: 0.86; 95% CI: 0.80–0.93) than the warfarin group. When stratified by CKD stage (stage I/II: 8.2%; stage III: 49.4%; stage IV: 12.8%; stage V/ESRD: 12.0%; stage unspecified: 17.6%), no significant interaction was observed for effects of apixaban versus warfarin on recurrent VTE or MB. In summary, apixaban was associated with a significantly lower risk of recurrent VTE and MB than warfarin among VTE patients with CKD. CKD stages did not have significant impact on treatment effects for recurrent VTE and MB.

Comparative Effectiveness and Safety of Extended Anticoagulant Therapy Among Medicare Beneficiaries with Venous Thromboembolism

▪Introduction: Approximately 30% of patients with venous thromboembolism (VTE) experience a recurrence within 10 years of the initial event with their recurrence risk peaking during the first 6-12 months. Two large randomized clinical trials AMPLIFY-EXT and PADIS-PE reported that extended treatment with apixaban and warfarin beyond 6 months of initial treatment reduced recurrent VTE without increasing the rate of major bleeding compared to placebo, respectively. Little is known about real-world effectiveness and safety of extended oral anticoagulation beyond 6 months of initial treatment for Medicare beneficiaries with VTE, despite the fact that VTE disproportionately affects the elderly. We assessed the effectiveness and safety of extended use of apixaban and warfarin beyond 6 months of initial treatment for prevention of recurrent VTE and adverse major bleeding events among Medicare beneficiaries with newly diagnosed VTE.Methods: A retrospective cohort study using 2014-2018 Medicare data (5% samples in 2014-2016 and 15% samples of Medicare beneficiaries in 2017-2018) was conducted for patients aged ≥18 years with a diagnosis of deep vein thrombosis or pulmonary embolism ascertained from inpatient claims. Patients were included if they initiated anticoagulants within 30 days of their first VTE diagnosis, completed 6 months of therapy defined as ≥83% proportion days covered with oral anticoagulants during the initial 6-month period, and received extended treatment with either apixaban or warfarin or no extended therapy. We compared the risks of recurrent VTE and major bleeding between apixaban, warfarin, and no treatment groups. To adjust for differences in baseline characteristics and clinical factors (e.g., HAS-BLED score, active cancer, and provoked VTE) between groups, we used the stabilized inverse probability treatment weighting (IPTW) method. Follow-up continued until the occurrence of the first event, switch to the comparator, disenrollment, death, or end of the study period. Multivariable Cox proportional hazards modeling with IPTW was used to obtain adjusted hazard ratios (aHR) and 95% confidence intervals (95%CI).Results: The study cohort (mean age=74 ±12 years, 40% male, 76% White) consisted of 2,315 users of extended apixaban treatment (83% with 5 mg twice a day and 17% with 2.5 mg twice a day; mean duration=6.2 months), 2,757 users of extended warfarin treatment (mean duration=8.2 months), and 2,328 patients with no extended treatment following completion of an initial 6 months of anticoagulant treatment. The incidence rates of recurrent VTE were 0.42, 1.73, and 1.72 per 100 person-years, and those of major bleeding were 2.28, 3.62, and 1.43 per 100 person-years in the apixaban, warfarin, and no treatment groups, respectively (Table 1). Compared to no extended treatment, the use of apixaban was associated with an 80% decreased risk of recurrent VTE (aHR=0.19, 95%CI=0.06-0.55) without increasing the risk of major bleeding (aHR=1.19, 95%CI=0.65-2.19); the use of warfarin did not lower the risk of recurrent VTE (aHR=0.75, 95%CI=0.42-1.37) but increased the risk of major bleeding (aHR=1.92, 95%CI=1.13-3.25). Compared to the use of warfarin, the use of apixaban was associated with a decreased risk of recurrent VTE (aHR=0.26, 95% CI=0.09-0.76) and no difference in major bleeding risk (aHR=0.61, 95%CI=0.36-1.06). These findings remained consistent in subgroup (e.g., patients with provoked vs. unprovoked VTE, patients with active cancer vs. those without, and patients with chronic kidney diseases vs. those without) and sensitivity analyses (e.g., ≥92% proportion days covered with oral anticoagulants during the initial 6-month period).Conclusions: Compared to no extended therapy, extended anticoagulation with apixaban was associated with a reduced risk of recurrent VTE without increasing the risk of major bleeding, whereas warfarin did not lower risk of recurrent VTE but increased the risk of major bleeding among Medicare beneficiaries with VTE. In the head-to-head comparison, the use of apixaban was more effective than warfarin in preventing recurrent VTE, without increasing the risk of major bleeding events. Our findings suggest that apixaban is an effective and safer option for extended treatment of VTE when compared to warfarin or no treatment among Medicare beneficiaries with VTE. [Display omitted] DisclosuresPark: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Kang: BMS/Pfizer Alliance American Thrombosis InvestigatorInitiated Research Program: Research Funding. Huang: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Lo-Ciganic: MERCK: Research Funding; BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Dietrich: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Murphy: North American Thrombosis Foundation: Honoraria. DeRemer: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding; Portola Pharmaceuticals: Current equity holder in publicly-traded company; BMS advisory board attendee: Honoraria.

Adherence Trajectories of Extended Direct-Acting Oral Anticoagulants and Risk of Recurrent Venous Thromboembolism and Major Bleeding: A Retrospective Cohort Study

▪Introduction: The optimal duration of extended oral anticoagulant treatment for patients with venous thromboembolism (VTE) beyond the initial 3 to 6 months of the treatment remains undetermined. Group-based trajectory modeling (GBTM) is a data-driven method that can categorize patients with similar longitudinal adherence patterns over time into distinct subgroups. This study identified distinct patient subgroups with similar adherence trajectories of extended treatment of direct-acting oral anticoagulants (DOACs), and then examined the association between adherence trajectories and the risk of recurrent VTE and major bleeding among patients with VTE.Methods: We identified patients ≥18 years with a diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE) from inpatient claims using 2013-2019 Truven Commercial and Medicare Supplemental database. Patients were included if they initiated anticoagulants within 30 days of their first VTE diagnosis, completed 6 months of therapy-defined as ≥83% proportion days covered (PDC) with oral anticoagulants during the initial 6-month treatment period, and had extended treatment with any DOACs or no extended therapy. Based on the monthly PDC as the DOAC adherence measure, we used GBTM to identify DOAC adherence trajectories during 6 months of the extended treatment. The final trajectory model was chosen by assessing the Bayesian information criteria, Nagin's criteria, and having at least 10% of patients in each trajectory group for improving clinical utility. We compared recurrent VTE and major bleeding among adherence trajectory subgroups. Patients were followed up from the initiation of the extended treatment until the occurrence of the study outcomes, discontinuation of DOACs, switching to warfarin, end of study period, or end of enrollment, whichever occurred first. Cox proportional hazard modeling with inverse probability treatment weighting (IPTW) was used to obtain hazard ratios (HR) and 95% confidence intervals (95% CI).Results: The study cohort (mean age=58.7 years and 51.1% males) consisted of 10,960 patients with extended treatment of DOACs (4,294 apixaban, 6,409 rivaroxaban, 238 dabigatran, and 19 edoxaban users) with a mean treatment duration of 7.7 months and 5,133 patients with no extended treatment following completion of an initial 6 months of anticoagulant treatment. The final GBTM models identified four distinct adherence trajectories for extended therapy including (1) patients with consistent adherence (group 1, 40.7%), (2) patients with gradually declining adherence (group 2, 14.3%), (3) patients with rapidly declining adherence (group 3, 13.1%), and (4) patients with no extended treatment (reference group, 31.9%) (Figure 1). The incidence rates of recurrent VTE were 18.6, 46.9, 84.1, and 160.7 per 10,000 person-years, and those of major bleeding were 61.0, 125.1, 168.3, and 48.7 per 10,000 person-years in group 1, group 2, group 3, and the reference group, respectively. After IPTW, demographics and clinical characteristics (e.g., HAS-BLED bleeding risk score, provoked VTE) were comparable across the four trajectory groups with <0.1 of the standardized mean difference for each pairwise comparison. Compared to the reference group, group 1 (HR=0.09, 95% CI=0.05-0.17) and group 2 (HR=0.16, 95% CI=0.04-0.58) had decreased risk of recurrent VTE without increasing risk of major bleeding (HR=1.26, 95% CI=0.76-2.10 in group 1, HR=2.28, 95% CI=0.96-5.36 in group 2). There was no difference in the risk of recurrent VTE (HR=0.32, 95% CI=0.09-1.16) in group 3 but they had an increased risk of major bleeding (HR=2.69, 95% CI=1.00-7.23). The findings were consistent across different types of DOACs, suggesting a class effect of DOACs as extended therapy.Conclusions: We identified 4 distinct trajectories of DOAC adherence during the 6 months of extended therapy among patients who completed 6 months of initial treatment. Compared to no extended treatment, persistent use of DOACs during extended treatment was associated with a lower risk of recurrent VTE without increasing major bleeding risk, whereas a rapid decline in adherence was associated with an increased risk of major bleeding with no difference in the risk of recurrence. Our findings provide evidence on the benefits of continuing and being adherent to extended anticoagulant treatment in patients with VTE without increasing the risk of major bleeding. [Display omitted] DisclosuresKang: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Jones: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Lo-Ciganic: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding; MERCK: Research Funding. DeRemer: BMS advisory board attendee: Honoraria; Portola Pharmaceuticals: Current equity holder in publicly-traded company; BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Dietrich: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Huang: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Murphy: North American Thrombosis Foundation: Honoraria. Park: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding.

Effectiveness and safety of apixaban vs warfarin among older venous thromboembolism patients stratified by race

Abstract Background Race has been identified as a risk factor for venous thromboembolism (VTE), with Black individuals having a higher risk of VTE compared to Caucasians. Black patients have been underrepresented in clinical trials evaluating anticoagulants for VTE. There has been limited evidence about the effects of anticoagulants for Black patients with VTE in routine clinical practice. Purpose To evaluate the risk of recurrent VTE, major bleeding (MB), and clinically relevant non-major (CRNM) bleeding among VTE patients initiating apixaban or warfarin stratified by race. Methods Older VTE patients (≥65 years) who initiated apixaban or warfarin were selected from the CMS Medicare database (September 2014–December 2017). Stabilized inverse probability treatment weighting (IPTW) was used to balance the differences between apixaban and warfarin cohorts. After IPTW, subgroup interaction analysis was conducted to evaluate if treatment effects were different between Black and White patients in the Medicare population. Due to small sample size, other races were not included in the interaction analysis. Cox proportional hazard models were used to evaluate if there was significant interaction (p&amp;lt;0.10) between treatment and race on recurrent VTE, MB, or CRNM bleeding. Results A total of 22,135 apixaban and 45,840 warfarin patients with VTE were included in the analysis. Post-IPTW, patient characteristics were balanced between apixaban and warfarin treatment cohorts. Apixaban patients had significantly lower risk of recurrent VTE, MB, and CRNM bleeding compared to warfarin patients (Figure). When stratified by race, 57,008 (83.9%) were White, 7,832 (11.5%) Black, and 3,135 (4.6%) other races. For both treatment cohorts, age was similar between Black (77.0–77.2 years) and White (77.4–77.5 years) patients. However, Black patients were more likely to have an inpatient VTE event (77.3–77.8% vs. 63.1–63.3%), a provoked VTE event (78.6–79.5% vs 69.4–69.6%), and a higher comorbidity index score (mean 4.1 vs. 2.7) compared to White patients with VTE. The incidence rates per 100 person-years of recurrent VTE (2.0–3.3 vs 1.4–2.2) and MB (7.4–10.1 vs 3.5–5.3) were also numerically higher for Black patients compared to White patients. Across both race groups, apixaban patients had a lower incidence rate of recurrent VTE, MB and CRNM bleeding compared to warfarin patients. No significant interaction was observed between treatment and race for recurrent VTE, MB, or CRNM bleeding (Figure). The findings within each race group were consistent with those of the overall VTE population. Conclusion Among older VTE patients, disparities were observed in VTE characteristics and clinical outcomes between Black and White patients. Across both race groups, apixaban had lower risk of recurrent VTE, MB, and CRNM bleeding compared to warfarin patients. Further studies are needed to identify optimal management strategies for Black patients with VTE. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Pfizer IncBristol-Myers Squibb Company

Effectiveness and safety of oral anticoagulants in the treatment of acute venous thromboembolism: a comparative cohort study in France

Abstract Background RCT evidence has shown that direct oral anti-coagulants (DOACs) are at least as effective and safer in terms of bleeding, compared to vitamin K antagonists (VKAs) in the treatment of acute venous thromboembolism (VTE). Purpose To compare the risks of recurrent VTE and of bleeding leading to hospitalisation, in patients treated with DOACs (each compared with VKAs) for acute VTE in a real-world setting. Methods A retrospective cohort study of treatment-naïve adult patients with VTE (patients with active cancer were excluded) treated with a DOAC (apixaban or rivaroxaban) or VKA, from 2013 to 2018. The French national health data system (SNDS) was used. After propensity score (PS) matching for each DOAC-VKA comparison, risks of bleeding (defined as principal diagnoses of hospital stays), 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 58137 treatment-naïve patients were included: 10775 (18.53%) VKAs, 10440 (17.96%) apixaban, and 36922 (63.51%) rivaroxaban. Patients initiating VKAs were older than those initiating apixaban or rivaroxaban (mean age in years: VKAs, 71; apixaban, 65; rivaroxaban, 60) and had a higher comorbidity burden (mean CCI score: VKAs, 1.55; apixaban, 0.91; rivaroxaban, 0.69). PS matched cohort sizes were: apixaban (n=7503) and rivaroxaban (n=9179). Crude risks of recurrent VTE per 100 patient-year (95% CI) were 4.99 (4.36; 5.70), 3.36 (2.88; 3.92) and 4.33 (4.03; 4.66) for VKAs, apixaban, and rivaroxaban respectively. For bleeding, the respective crude risks were 5.21 (4.57; 5.94), 1.84 (1.49; 2.28), and 2.64 (2.41; 2.90). For all-cause mortality, the respective crude risks were 12.23 (11.26; 13.27), 4.69 (4.11; 5.34), and 2.73 (2.49; 2.99). Adjusted hazard ratios for the endpoints are presented in the table. Conclusions Apixaban was associated with a lower risk of recurrent VTE and bleedings requiring hospitalisation compared with VKAs. Similar trends in risk reduction for these outcomes were observed for rivaroxaban compared with VKAs but without reaching statistical significance. Both DOACs were associated with lower risk of all-cause mortality compared with VKAs. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): BMS/Pfizer alliance

Effectiveness and Safety of Apixaban Versus Warfarin Among Older Patients with Venous Thromboembolism with Different Demographics and Socioeconomic Status.

IntroductionImpact of demographics and socioeconomic status (SES) on anticoagulant treatment outcomes among patients with venous thromboembolism (VTE) is not well understood. This study evaluated risks of recurrent VTE, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) among older patients with VTE initiating apixaban or warfarin stratified by demographics and SES.MethodsAdult patients (≥ 65 years) who initiated apixaban or warfarin after a VTE event were selected from the US CMS Medicare database (September 2014–December 2017). Stabilized inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Patients were stratified by age, gender, race, and SES. For each subgroup, Cox proportional hazard models were used to evaluate if there was a significant interaction (p < 0.10) between treatment and subgroup for recurrent VTE, MB, and CRNMB.ResultsIn total, 22,135 apixaban and 45,840 warfarin patients with VTE were included. Post-IPTW, patient characteristics were balanced between treatment cohorts. In older patients, apixaban treatment was associated with significantly lower risks of recurrent VTE (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.52–0.79), MB (HR 0.65; 95% CI 0.57–0.75), and CRNMB (HR 0.79; 95% CI 0.75–0.85) versus warfarin. When stratified by demographics and SES, higher incidence rates of recurrent VTE, MB, and CRNMB were observed for black vs white patients and patients with lower vs higher SES. Comparison of apixaban with warfarin by different demographic and SES subgroups showed generally consistent results as the overall analysis. For most subgroups, no significant interaction was observed between treatment and subgroup strata for recurrent VTE, MB, and CRNMB.ConclusionAmong older patients with VTE initiating apixaban or warfarin, higher rates of recurrent VTE and bleeding were observed in black patients and patients with lower SES. Apixaban had a lower risk of recurrent VTE, MB, and CRNMB compared to warfarin. Analyses of demographic and SES subgroups showed consistent findings.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01918-0.