Recurrent Venous Thromboembolism Events Research Articles

Anticoagulation strategies and recurrence of venous thromboembolic events in patients with sickle cell disease: a systematic review and meta-analysis.

Sickle cell disease (SCD) results in many complications including an increased risk of developing venous thromboembolic events (VTEs) and an increased risk of mortality as a result. We conducted a systematic review using multiple databases to compare the efficacy of different anticoagulation in preventing recurrence, development of bleeding, progression of thrombus, and mortality in patients with SCD and a venous thrombotic event. Eight hundred seventy-one studies were screened and six studies were included. Among patients with SCD who experienced a VTE and were anticoagulated, the overall recurrence of VTE was 27.6% (95%CI 23.5-31.9). The overall progression to pulmonary embolism (PE) was 11.7% (95%CI 4.3-22.1). The overall bleeding rate was 14.1% (95%CI 7.8-21.9) and the overall mortality was 3.7% (95%CI 0.8-8.5). Based on observational studies, there did not appear to be differences between anticoagulant classes for the above adverse outcomes. Significant heterogeneity in the patient population and outcome measures limited the interpretation of the results. More studies, specifically randomized trials, are needed to help direct appropriate management of VTE's in patients with sickle cell disease (PROSPERO ID: 236,208).

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.

0829 Workup of Nocturnal Hypoxemia Leads to Diagnosis of Patent Foramen Ovale

Abstract Introduction Patent foramen ovale (PFO) in adults often remains asymptomatic until clinical manifestations such as cryptogenic stroke, migraine headache, air embolism, hypoxemia, or platypnea-orthodeoxia syndrome occur. In this case, prior workup of cryptogenic stroke failed to identify a PFO that was diagnosed after further investigation of polycythemia which revealed nocturnal hypoxemia on polysomnogram. Report of Cases: A 60-year-old male with history of recurrent venous thromboembolic events (VTE), secondary polycythemia, and cryptogenic strokes was referred for a polysomnogram during the evaluation of polycythemia. Over the span of six years, he had multiple cryptogenic strokes and VTEs in the setting of polycythemia and normal hypercoagulability labs. Further evaluation suggested secondary polycythemia after serum erythropoietin and JAK2 mutation testing were negative. The patient was a never smoker without evidence of malignancy or renal disease leading to suspicion that his polycythemia was due to hypoxemia despite normal oxygen saturations during point of care evaluations. He frequently reported shortness of breath during appointments. During a polysomnogram, the patient was found to have a total apnea-hypopnea index of fewer than 5 events per hour but demonstrated hypoxemia with 49.7% of total sleep time spent below an oxygen saturation of 90%. He was referred to pulmonology for further evaluation that showed normal resting oxygen saturation, no desaturation on a six-minute walk test, mild restrictive defect on pulmonary function testing, and a normal chest computed tomography with angiography. Prior transthoracic echocardiogram had demonstrated an atrial septal aneurysm without communication between the atrial chambers. No evidence suggestive of a right-to-left shunt was found on lateral imaging of the brain during a ventilation-perfusion scan. Further evaluation of the aneurysmal atrial septum on transesophageal echocardiogram with an agitated saline bubby study demonstrated a patent foramen ovale with a right-to-left shunt. In the setting of hypoxia leading to secondary polycythemia, the patient was scheduled for PFO closure. Conclusion Hypoxemia out of proportion to sleep-disordered breathing on polysomnogram should prompt further evaluation. Despite multiple prior strokes, our patient’s PFO had gone undiagnosed until polycythemia prompted a polysomnogram that demonstrated isolated nocturnal hypoxemia and prompted a further workup. Clinically significant hypoxemia is an indication for PFO closure. Support (If Any)

Recurrence rate of venous thromboembolic events in granulomatosis with polyangiitis.

ObjectiveThe incidence of first-time venous thromboembolic events (VTEs) is high in granulomatosis with polyangiitis (GPA). The incidence of recurrent VTEs is unknown. We aimed to describe the recurrence rate of second VTEs in patients with GPA.MethodsRetrospective chart review was performed in patients with GPA and at least one VTE at a single centre from 2002 to 2016. Inclusion criteria were 1990 ACR criteria or 2012 Revised International Chapel Hill nomenclature for GPA, at least two follow-up visits, at least one VTE during the study period, and VTE occurrence after or within 3 months before GPA diagnosis. Second VTE event-free survival rates were estimated.ResultsOut of 147 patients initially screened for GPA and with at least one VTE, 84 met inclusion criteria. Median age at first VTE was 57 years. Incidence rate for second VTE was 8.4 events per 100 patient-years (95% CI: 5.7, 12.3). Eighty-three point three per cent of first VTEs and 57.7% of second VTEs occurred when disease was active (P < 0.001). Renal involvement and constitutional symptoms at the time of first VTE were associated with VTE recurrence.ConclusionGPA has a high rate of VTE recurrence compared with the reported data in the general population with unprovoked VTE. Our results suggest that VTE in GPA is a recurrent co-morbidity, not always during active vasculitis, and more so in those with renal involvement and constitutional symptoms at the time of first VTE.

Effectiveness and Safety of Extended Oral Anticoagulant Therapy in Patients with Venous Thromboembolism: A Retrospective Cohort Study.

Limited real-world evidence exists for effectiveness and safety of extended oral anticoagulation beyond 6months of initial treatment in prevention of recurrent venous thromboembolism (VTE) and adverse major bleeding events among patients with VTE. Using MarketScan Commercial and Medicare Supplemental databases (2013-2019), we conducted a retrospective cohort study to compare the risk of recurrent VTE and major bleeding events during extended treatment among patients with VTE who completed the 6-month initial treatment and received extended oral anticoagulant treatment with apixaban, warfarin, or no extended treatment. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards modeling with inverse probability treatment weighting. We identified 14,818 patients with extended treatment of apixaban (n=4,338), warfarin (n=5,298), or no extended treatment (n=5,182). Compared with no extended treatment, apixaban use was associated with decreased risk of recurrent VTE (HR: 0.10, 95% CI: 0.04-0.26) without increased risk of major bleeding events (HR: 1.06, 95% CI: 0.52-2.17); warfarin use was associated with decreased risk of recurrent VTE (HR: 0.23, 95% CI: 0.12-0.44) but with increased risk of major bleeding events (HR: 2.64, 95% CI: 1.51-4.59). Compared with warfarin, apixaban use was associated with decreased risk of major bleeding events (HR: 0.42, 95% CI: 0.22-0.80) but no difference in risk of recurrent VTE (HR: 0.46, 95% CI: 0.15-1.36). In a real-world clinical setting, extended anticoagulation with apixaban or warfarin was associated with decreased risk of recurrent VTE compared with no extended treatment, and apixaban had a better safety profile with fewer major bleeding events compared with warfarin among commercially insured patients with VTE.

In Search of the Appropriate Anticoagulant-Associated Bleeding Risk Assessment Model for Cancer-Associated Thrombosis Patients.

Simple SummaryPatients with venous thromboembolism events in the context of cancer should receive anticoagulants as long as the cancer is active. Therefore, a tailor-made anticoagulation strategy should rely on an individualized assessment of the risks of recurrent venous thromboembolism and anticoagulant-associated bleeding. No existing risk assessment model for anticoagulant-associated bleeding risk has been validated for cancer-associated thrombosis. To obtain a better risk assessment model to assess anticoagulant-associated bleeding risk in cancer-associated thrombosis patients, we deemed it necessary to answer questions related to how and when to assess anticoagulant-associated bleeding risk as well as what factors to assess for which patients. Patients with venous thromboembolism events (VTE) in the context of cancer should receive anticoagulants as long as the cancer is active. Therefore, a tailor-made anticoagulation strategy should rely on an individualized risk assessment model (RAM) of recurrent VTE and anticoagulant-associated bleeding. The aim of this review is to investigate the applicability of the currently available RAMs for anticoagulant-associated bleeding after VTE in the CAT population and to provide new insights on how we can succeed in developing a new anticoagulant-associated bleeding RAM for the current medical care of CAT patients. A systematic search for peer-reviewed publications was performed in PubMed. Studies, including systematic reviews, were eligible if they comprised patients with VTE and used a design for developing a prediction model, score, or other prognostic tools for anticoagulant-associated bleeding during anticoagulant treatment. Out of 15 RAMs, just the CAT-BLEED was developed for CAT patients and none of the presented RAMs developed for the VTE general population were externally validated in a population of CAT patients. The current review illustrates the limitations of the available RAMs for anticoagulant-associated bleeding in CAT patients. The development of a RAM for bleeding risk assessment in patients with CAT is warranted.

ANTI-PHOSPHOLIPID SYNDROME INDUCED POST COVID INFECTION: A CASE REPORT

Anti- phospholipid syndrome (APS) is an autoimmune prothrombotic disease characterized by persistently elevated antiphospholipid antibodies, resulting in recurrent arterial and venous thromboembolic events. The deep veins of the lower limbs and the cerebral arterial circulation are the most common sites of venous and arterial thrombosis, respectively [1] The other major clinical manifestations of the antiphospholipid syndrome are obstetrical. They include the unexplained death of one or more morphologically normal fetuses at or beyond the 10th week of gestation, the premature birth of one or more morphologically normal neonates before the 34th week of gestation because of either eclampsia or severe preeclampsia, and three or more unexplained, consecutive spontaneous abortions before the 10th week of gestation [2] Thrombotic events post COVID 19 infection has been described since the beginning of pandemic in 2019[3]. Autopsy reports have shown that most thromboses are located in the lung, although they have also been observed in other organs such as the skin and kidneys. SARS-CoV2 infection induces a generalized prothrombotic state, which is attributed to a combination of factors such as hypoxia, excess cellular apoptosis, and mainly to overactivation of the immune system [4]. Considering the high rate of mortality due to coagulation abnormalities and thrombosis among coronavirus disease 2019 patients, it is important to pay attention to the differential diagnoses of coronavirus disease 2019 and other diseases following thrombotic events [5].

Non-vitamin K antagonist oral anticoagulants in venous thromboembolism patients: a meta-analysis of real-world studies

BackgroundThe real-world studies on recurrent venous thromboembolism (VTE) and bleeding events of non-vitamin K antagonist oral anticoagulants (NOACs) in VTE patients have reported conflicting findings. Our study aimed to provide the direct comparison evidence of different NOACs for VTE patients in clinical practice settings.MethodsSearch of the medical literature was conducted using PubMed, Web of Science, EMBASE, Clinical Trials.gov, and the Cochrane Library from inception to March 22, 2021. Among the 19,996 citations retrieved, a total of 63,144 patients from 6 studies were analyzed. Clinical outcomes included recurrent VTE, death, and different bleeding events.ResultsAdjusted hazard ratio (HR) analysis suggested that apixaban had significant lower bleeding riskthan rivaroxaban (major, minor and any bleeding: HR = 0.61, 0.56, 0.70; p = 0.008, < 0.0001, 0.006, respectively), but no statistics difference found in recurrent VTE events (HR = 1.02, 95% confidence interval (CI) 0.71–1.47, p = 0.93). There was no significant difference of major bleeding between dabigatran and rivaroxaban (odds ratios (OR) = 0.41, 95% CI 0.09–1.90, p = 0.25), apixaban and dabigatran (OR 0.64, 95% CI 0.15–2.72, p = 0.83). No significant difference was found in the comparison of edoxaban and other NOACs in VTE recurrence, major bleeding and composite outcome.ConclusionsIn the prevention of bleeding events, apixaban was associated with a lower risk than rivaroxaban, but equivalent efficacy for different NOACs in prevention of recurrent VTE. Evidence generated from the meta-analysis based on real-world data can help to guide selection between apixaban and rivaroxaban in routine clinical practice.Trial registration: This systematic review and meta-analysis were conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis and Meta-analysis of Observational Studies in Epidemiology statements and was registered with PROSPERO (CRD42019140553).

Extended anticoagulation treatment for cancer‐associated thrombosis—Rates of recurrence and bleeding beyond 6 months: A systematic review

BackgroundPatients with cancer‐associated venous thromboembolism (VTE) are recommended to receive treatment with therapeutic anticoagulation for at least 3–6 months. Little data exist on extended treatment beyond 6 months. ObjectiveTo comprehensively summarize the best available evidence on incidence of recurrent VTE and major bleeding 6–12 months after the index event in patients with cancer‐associated VTE. Patients/MethodsWe systematically screened biomedical databases (MEDLINE, Embase, CENTRAL) to identify studies reporting recurrent VTE and/or bleeding events between 6 and 12 months after a diagnosis of cancer‐associated VTE. Based on the observed heterogeneity in study design, setting, patient cohort characteristics, anticoagulation strategies, and outcome rates, no overall quantitative estimate of outcome rates was calculated. ResultsWe screened 2597 publications and identified 11 eligible studies matching predefined in‐/exclusion criteria, reporting on 3019 patients specifically during the 6‐ to 12‐month period post–index VTE. Overall rates of recurrent VTE in this timeframe varied substantially (1%–12%), with the highest risk observed in the patient subgroup with residual vein thrombosis present at 6 months randomized to receive no anticoagulation (13%–15%). Reported rates of major bleeding between 6 and 12 months were between 2% and 5%. ConclusionsIn this systematic review, we provide a comprehensive and structured summary of the best available evidence on recurrence and bleeding risk between 6 and 12 months after cancer‐associated VTE. VTE recurrence remains common beyond 6 months and continuation of different anticoagulation strategies has an acceptable safety profile indicated by lower bleeding rates. These findings support guideline recommendations to continue anticoagulation treatment beyond 6 months in patients with active cancer.

Inflammatory Bowel Disease: An Indication to Screen for Thrombophilia?

Inflammatory bowel diseases (IBD) are systemic conditions characterized by multiple intestinal and extra-intestinal manifestations related to the associated chronic inflammatory state. Among their diverse extra-intestinal complications, venous thromboembolism (VTE) remains one of the most under recognized causes of morbidity and mortality in these patients, highlighting the need for a better understanding of the underlying mechanism of hypercoagulability, in addition to the role of acquired and inherited risk factors that further increase the risk of thrombosis with its impact on patients’ outcomes. We hereby present a review of the data regarding thrombosis in the setting of IBD, elucidating the possible role for screening in this high-risk category of patients and specifically in areas where inherited thrombophilia is expected to be highly prevalent, reporting two patients with IBD, one who developed a cerebrovascular event and another one who had recurrent VTE events; nevertheless, both of them had inherited thrombophilic mutations. The identification of specific genetic abnormalities in those patients reintroduces the controversy related to the need to screen a specific category of patients with IBD for hereditary thrombophilia, especially in regions characterized by a higher prevalence of such thrombophilic alterations.

Comparison of effectiveness and safety for low versus full dose of apixaban during extended phase oral anticoagulation in patients with venous thromboembolism.

The optimal dose of apixaban therapy to prevent asecondary venous thromboembolism (VTE) event remains unconfirmed. To investigate the effects of extended phase use of apixaban (2.5 vs. 5mg twice daily) beyond 6 months of initial treatment on the risk of recurrent VTE and major bleeding events among patients with a history of VTE. A retrospective cohort analysis of two large national insurance claims databases was conducted for patients diagnosed with VTE. Cox proportional hazard models after propensity score matching were used to compare the risk of recurrent VTE and major bleeding. There were no detected differences in recurrent VTE or major bleeding events between patients prescribed low versus full dose apixaban. This study provides evidence that apixaban 2.5mg twice daily is an alternative option for extended phase therapy for risk reduction of VTE recurrence compared to apixaban 5mg twice daily.

Statins for venous event reduction in patients with venous thromboembolism: A multicenter randomized controlled pilot trial assessing feasibility

BackgroundStatins may reduce the risk for recurrent venous thromboembolism (VTE); however, no randomized trials have explored this hypothesis. We performed a pilot randomized trial to determine feasibility of recruitment for a larger trial of secondary VTE prevention with rosuvastatin. MethodsPatients with a newly diagnosed symptomatic proximal deep vein thrombosis and/or pulmonary embolism, receiving standard anticoagulation, were randomly allocated to adjuvant rosuvastatin 20 mg once daily for 180 days or no rosuvastatin for 6 months. ResultsBetween November 2016 and December 2019, 3391 patients were assessed for eligibility in six centers. Of these patients, 1347 (39.7%) were eligible and approached for participation in the trial and 312 (23.1%) were randomized. The mean rate of randomization was 8.2 ± 4.3 patients per month. During follow‐up, five recurrent VTE events were observed, three (1.9%) in the rosuvastatin group (two pulmonary embolism, one deep vein thrombosis), and two (1.3%) in the control group (two pulmonary embolism; P = 0.68). One major arterial event occurred in the rosuvastatin arm and none in the control arm (0.6% vs. 0%, P = 0.50). ConclusionThis pilot trial supports the feasibility of a larger scale randomized controlled trial to determine the efficacy of adjuvant rosuvastatin for the secondary prevention of VTE.

Factor Xa inhibitor for venous thromboembolism management in patient with cancer: a systematic review and meta-analysis.

Background: An earlier systematic review reported no differences in the incidence of recurrent venous thromboembolism and major bleeding between factor Xa inhibitors and standard anticoagulation. The present meta-analysis aimed to assess the effectiveness of factor Xa inhibitors for the management of venous thromboembolism (VTE), specifically in patients with cancer, as there were more randomized clinical trials (RCTs) available. Methods: The PubMed and Cochrane Library databases were systematically screened for all RCTs assessing factor Xa inhibitor efficacy for VTE management in cancer patients. Using RevMan 5.3, we performed a Mantel-Haenszel fixed-effects meta-analysis of the following outcomes: recurrent VTE, VTE events, and major bleeding rates. Results: We identified 11 studies involving 7,965 patients. Factor Xa inhibitors were superior in preventing VTE recurrence, compared to low-molecular-weight heparin (LMWH) (OR 0.60; 95% CI 0.45-0.80; P < 0.01) and vitamin K antagonists (VKA) (OR 0.51; 95% CI 0.33-0.78; P < 0.01). As prophylaxis, factor Xa inhibitors had a similar rate of VTE compared to VKAs (OR 1.08 [95% CI 0.31-3.77]; P = 0.90) and a lower rate compared to placebo (OR 0.54 [95% CI 0.35-0.81]; P < 0.01). Major bleeding rates were higher with factor Xa inhibitors than with LMWHs (OR 1.34 [95% CI 0.83-2.18]; P = 0.23), but significantly lower than VKAs (OR 0.71 [95% CI 0.55-0.92]; P < 0.01). Conclusions: Factor Xa inhibitors are effective for VTE management in patients with cancer; however, they are also associated with an increased bleeding risk compared to LMWH, but decreased when compared to VKA.

Cancer‐Associated ThrOmboSIs – Patient‐Reported OutcoMes With RivarOxaban (COSIMO) – Baseline characteristics and clinical outcomes

BackgroundPatients with cancer‐associated thrombosis (CAT) have a high risk of recurrent venous thromboembolic events, which contribute to significant morbidity and mortality. Direct oral anticoagulants may provide a convenient treatment option for these patients. ObjectivesTo assess clinical characteristics and outcomes of patients with active cancer changing to rivaroxaban after ≥4 weeks of standard therapy for the treatment of venous thromboembolism (VTE) in clinical practice. This analysis focused on secondary outcomes of Cancer‐associated thrOmboSIs – Patient‐reported outcoMes with rivarOxaban (COSIMO). PatientsCOSIMO was a multinational, prospective, noninterventional, single‐arm cohort study. Overall, 505 patients received at least one dose of rivaroxaban; 96.6% changing from low‐molecular‐weight heparin, 1.6% from a vitamin K antagonist, and 1.8% from fondaparinux. ResultsMost patients had solid tumors (n = 449; 88.9%) and approximately half of these patients had metastases. The qualifying venous thromboembolic event was deep vein thrombosis (DVT) in 45.3% of patients, pulmonary embolism (PE) in 37.2% of patients, DVT with PE in 9.7% of patients, and catheter‐associated DVT in 7.5% of patients. Approximately 75.1% of patients received rivaroxaban for at least 3 months; 150 (29.7%) patients received concomitant chemotherapy during the study. VTE recurrence, major bleeding, nonmajor bleeding, and major adverse cardiovascular events occurred in 18 (3.6%), 18 (3.6%), 81 (16.0%), and 12 (2.4%) patients, respectively. ConclusionsIn patients with CAT who changed to rivaroxaban treatment after ≥4 weeks of standard therapy, the observed incidence proportions of recurrent VTE and bleeding events were in keeping with the recognized effectiveness and safety profile of rivaroxaban for the treatment of CAT.

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.

Extended Anticoagulant Treatment with Full- or Reduced-Dose Apixaban in Patients with Cancer-Associated Venous Thromboembolism: Rationale and Design of the API-CAT Study.

Cancer-associated thrombosis (CT) is associated with a high risk of recurrent venous thromboembolic (VTE) events that require extended anticoagulation in patients with active cancer, putting them at risk of bleeding. The aim of the API-CAT study (NCT03692065) is to assess whether a reduced-dose regimen of apixaban (2.5 mg twice daily [bid]) is noninferior to a full-dose regimen of apixaban (5 mg bid) for the prevention of recurrent VTE in patients with active cancer who have completed ≥6 months of anticoagulant therapy for a documented index event of proximal deep-vein thrombosis and/or pulmonary embolism. API-CAT is an international, randomized, parallel-group, double-blind, noninferiority trial with blinded adjudication of outcome events. Consecutive patients are randomized to receive apixaban 2.5 or 5 mg bid for 12 months. The primary efficacy outcome is a composite of recurrent symptomatic or incidental VTE during the treatment period. The principal safety endpoint is clinically relevant bleeding, defined as a composite of major bleeding or nonmajor clinically relevant bleeding. Assuming a 12-month incidence of the primary outcome of 4% with apixaban and an upper limit of the two-sided 95% confidence interval of the hazard ratio <2.0, 1,722 patients will be randomized, assuming an up to 10% loss in total patient-years (β = 80%; α one-sided = 0.025). This trial has the potential to demonstrate that a regimen of extended treatment for patients with CT beyond an initial 6 months, with a reduced apixaban dose, has an acceptable risk of recurrent VTE recurrence and decreases the risk of bleeding.

National guidelines on the management of venous thromboembolism: Joint guideline of the Turkish Society of Cardiovascular Surgery, National Society of Vascular and Endovascular Surgery, and Phlebology Society.

These evidence-based guidelines from the Turkish Society of Cardiovascular Surgery, National Society of Vascular and Endovascular Surgery, and Phlebology Society intend to support clinicians in best decisions regarding the treatment of venous thromboembolism (VTE). The Editor was selected by the three national societies and was tasked with the recruitment of the recognized panel. All financial support was solely derived from the sponsoring societies without the direct involvement of industry or other external stakeholders. The panel prioritized clinical questions and outcomes according to their importance for clinicians in terms of VTE. The panel agreed on 42 recommendations under 15 headings for the diagnosis, initial management, secondary prevention of VTE, and treatment of recurrent VTE events. Important recommendations included the use of ultrasonography, preference for home treatment over hospital treatment for uncomplicated VTE, preference for direct oral anticoagulants (DOACs) over vitamin K antagonists for primary treatment of cancer and non-cancer-related VTE, extended or indefinite anticoagulation with DOACs in selected high-risk patients. Early catheter-directed thrombectomy was recommended in only young symptomatic patients with a diagnosis of fresh iliofemoral deep vein thrombosis.

Evaluation of direct oral anticoagulant use for cancer-associated venous thromboembolism (VTE) in lung cancer.

243 Background: National Comprehensive Cancer Network recommends direct oral anticoagulants (DOACs) as preferred agents for treatment of cancer associated VTE in patients without gastric or gastroesophageal lesions. Currently at Massachusetts General hospital (MGH), DOACs are used in treatment of cancer associated VTE. This study was performed to evaluate the safety and efficacy of DOACs for treatment of VTE in patients with metastatic lung cancer. Methods: Retrospective chart review of patients at MGH with diagnosis of metastatic lung cancer who were prescribed edoxaban, rivaroxaban, or apixaban for treatment of VTE between January 2018 and January 2021 was performed. Patients were identified using electronic medical record reports. Data was collected on age, anticoagulation regimen, intent of anticoagulation therapy, presence of brain metastasis, renal function, liver function and platelet counts. The primary outcome was to assess the incidence of treatment failure, defined as VTE recurrence or major bleeding leading to a change in anticoagulation therapy. Results: 152 patients were evaluated, of which 57 received apixaban, 44 rivaroxaban, and 7 edoxaban. Most (n = 93) patients received enoxaparin for 14-90 days prior to transitioning to DOACs. Median age and creatinine clearance were 69 years and 63 mL/min, respectively. All patients had platelet count ≥ 50K/uL. Brain metastasis was present in n = 39 patients. Pulmonary embolism (PE)(n = 98), deep vein thrombosis (DVT) (n = 52), or both (n = 2) were the indication for DOAC therapy. Bleeding occurred in 14 patients including gastrointestinal bleeding (n = 5), hematuria (n = 4), epistaxis (n = 1), and hemoptysis (n = 4). Among patients with bleeding events, 7 received rivaroxaban and 7 received apixaban. Major recurrent VTE while on DOACs occurred in 5 of patients, including DVT (n = 2) and PE (n = 3). Patients with recurrent VTE received rivaroxaban (n = 7), apixaban (n = 3) and edoxaban (n = 1). All patient whom experienced bleeding and VTE were ≥ 60 years old. Brain metastasis was present in n = 2 of patients with bleeding events and n = 2 patients with recurrent VTE. Majority of patients (n = 93) received enoxaparin for 14-90 days prior to transitioning to DOACs. The median interval between initiation of DOACs and bleeding was 60 days (range 30-365) and recurrent VTE event was 90 days (range 60‐365). Conclusions: The results of this study suggest that outcomes of DOAC use for the treatment of cancer-associated VTE in patients with metastatic lung cancer are comparable to the results of large randomized controlled trials. DOAC therapy is a safe and effective anticoagulation option for lung cancer patients with cancer-associated thromboembolism.

Retrospective Study of Bleeding Risk with Concomitant Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor and Anticoagulation.

Patients with cancer are at higher risk for venous thromboembolism (VTE) and bleeding, in turn complicating anticoagulant therapy. An added complexity is the toxicity profile of agents used to treat certain cancers, namely the vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs), which are associated with both thromboembolism and hemorrhages. The purpose of this study was to evaluate whether patients taking concurrent VEGF TKI and therapeutic anticoagulant were at higher risk for bleeding compared with patients taking VEGF TKI alone. This was a single-center, retrospective chart review of patients who underwent treatment with a VEGF TKI with or without anticoagulant. The primary outcome included comparison of major bleeding rates between groups. Secondary outcomes included comparison of composite major and minor bleed rates and assessment of VTE incidence and recurrence among patients treated with a VEGF TKI and VEGF TKI plus anticoagulant, respectively. A total of 184 and 74 patients were included in the VEGF TKI alone and VEGF TKI + anticoagulant groups, respectively. Major bleeding events occurred in 6 of 184 patients (3.3%) and 6 of 74 patients (8.1%), respectively (p = .095). Composite major and minor bleeding events occurred in 22 of 184 (13.6%) and 17 of 74 (23%), respectively (p = .026). A total of 26 of 258 patients (10.1%) experienced a VTE event while taking a VEGF TKI, and 1 of 26 (3.8%) experienced a recurrent VTE event while taking a VEGF TKI plus anticoagulant. Patients who received concomitant VEGF TKI plus anticoagulant had increased incidence of bleeding, although prospective studies are needed to further explore this association. The current study showed that use of concomitant vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGF TKI) and therapeutic anticoagulation was associated with an increased risk of composite bleeding events, although at comparable rates between patients treated with VEGF TKI plus direct oral anticoagulant (DOAC) versus VEGF TKI plus non-DOAC anticoagulant. This suggests that when anticoagulation is indicated in a patient receiving a VEGF TKI, the novel DOACs may be a safe alternative to historical anticoagulants (warfarin and enoxaparin). These results fill a gap in the literature and will help guide treatment decisions for patients requiring concurrent VEGF TKI and anticoagulation.

Anticoagulation for the Treatment of Acute Venous Thromboembolism a Systematic Review and Network Meta-Analysis

Background: There are several anticoagulation strategies are suggested for patients with acute venous thromboembolism (VTE), however proof, especially for cancer-associated VTE, is lacking of which strategy is optimal choice. We aimed to compare efficacy and safety outcomes among various anticoagulation strategies for patients with VTE using a systematic review and network meta-analysis. Methods: A systematic literature search was conducted using PUBMED, EMBASE, and Cochrane Library Central Register of Controlled Trials and clinical trial registries from inception through June 1, 2021. We search for randomized clinical trials (RCTs) comparing the recurrent VTE and bleeding outcomes of various anticoagulation strategies (low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), or fondaparinux combined with vitamin K antagonists(VKA)); direct oral anticoagulants) for patients with acute VTE(noncancer or cancer-associated). Extraction of clinical outcomes were performed independently by two authors. A Bayesian network meta-analysis was applied to analyze the data. The primary efficacy endpoint was recurrent VTE episodes, the primary safety endpoint was major bleeding episodes. Secondary efficacy endpoints were fatal recurrent venous thromboembolism, the secondary safety endpoints were fatal bleeding episodes, all-cause mortality and major gastrointestinal bleeding. Results: 12117 citations were identified, 9850 unique citations, 54 RCTs met the inclusion criteria. Included trials recruited 49952 VTE participants with cancer or non-cancer. The findings showed that UFH-VKA likely increases recurrent VTE compared to LMWH-VKA (hazard ratio ((HR) 1·44(1·16,1·80), apixaban was probably the most effective strategy (surface under the cumulative ranking curve (SUCRA) 87·6%). Subgroup analysis for VTE patients with cancer shown that LMWH (HR 0·61(0·40,0·89)) and apixaban (HR 0·40(0·21,0·66)) were associated with less recurrent VTE events compared with LMWH-VKA. Apixaban (HR 0·44(0·24,0·73)) lowered the rate of major bleeding compared with the LMWH–VKA. The apixaban was probably the safest strategy (SUCRA 96·5%). For patients with cancer-associated acute VTE, although apixaban group experienced less major bleeding events compared with LMWH-VKA, it was not statically significant (HR 0·80(0·36,1·55)). Interpretation: Apixaban seems to be superior to other anticoagulation strategies for treatment of VTE with cancer. Funding: This work received research grant from The Second Hospital of Anhui Medical University(Hefei, Anhui 230601, China). Grant number: LBSART202007. Declaration of Interest: None to declare.