Optimal Duration Of Anticoagulant Therapy Research Articles

Is it safe to discontinue anticoagulant after surgical treatment of varicose vein disease, which caused pulmonary embolism?

Superficial vein thrombosis, which is mostly caused by lower extremity varicose vein disease, can be complicated by pulmonary embolism. At the same time, the optimal duration of anticoagulant therapy for pulmonary embolism originated from varicose vein thrombosis is still under debate. On the one hand, the presence of varicose veins is considered a small risk factor for the development of venous thromboembolic events, which persistence determines an increased risk of relapse and requires prolonged anticoagulant therapy. On the other hand, elimination of varicose veins is associated with reduced risk of subsequent venous thromboembolic events. The article describes a clinical case of recurrent pulmonary embolism after surgical treatment of varicose vein disease, which caused primary pulmonary embolism. A 45-year-old patient suffering from left lower extremity varicose vein disease for 5 years was admitted to the intensive care unit with suspected pulmonary embolism. The further examination revealed signs of thrombotic occlusion of the segmental and subsegmental branches of the pulmonary arteries bilaterally and the middle lobe branch of the right pulmonary artery, as well as signs of the right-sided heart overload. In this case, pulmonary embolism was found to originate from thrombosis of the trunk of the great saphenous vein ofthe left lower extremity with a proximal border at the level of the lower leg. No signs of deep vein involvement were detected. The parenteral anticoagulant therapy initiated in the hospital was followed by switching to therapeutic doses of rivaroxaban. The signs of recanalization of involved veins were identified after 6 months of treatment, and it was decided to perform endovenous laser coagulation of the trunk of the great saphenous vein combined with mini-phlebectomy of varicose tributaries on continuous oral anticoagulant therapy. The rivaroxaban therapy was completed a month after intervention. However, 7 days later the patient was diagnosed with repeated symptomatic pulmonary embolism, which originated from thrombosis of the left popliteal vein. It was recommended to resume anticoagulant therapy of indefinite duration. The article discusses the issues of optimal duration of treatment for pulmonary embolism originated from thrombosis of superficial varicose veins, as well as the possible timing of completion of anticoagulant therapy after the intervention.

Short versus long-term anticoagulation for left ventricular thrombosis resolution during vitamin k antagonist therapy

Abstract Background The optimal duration of anticoagulant therapy to achieve thrombus resolution and prevent cardioembolic events in left ventricular thrombosis (LVT) has not yet been established. Purpose The purpose of our study is to evaluate the incidence of LVT resolution at 3 versus 12 months of vitamin K antagonists (VKAs) therapy. Methods Consecutive patients diagnosed with LVT and treated with VKAs for at least 12 months at 5 anticoagulant outpatient clinics in Italy were retrospectively included. The primary effectiveness outcome was on-treatment thrombus resolution while the secondary was objectively documented on-treatment acute ischemic stroke, peripheral embolism, and myocardial infarction at 12-months follow-up. Safety outcomes were on-treatment major and clinically relevant non-major bleedings at 12-months follow-up as defined by the ISTH criteria. Cumulative incidences of thrombus resolution with 95% confidence intervals (CIs) were calculated while other outcomes were descriptively reported. Multivariable Cox hazards models were calculated using age, sex, reduced left ventricular ejection fraction (EF < 35%), VKAs monotherapy, and time in therapeutic range (TTR) below 60% as covariates for thrombus persistence at 12-months of follow-up. Results Out of 95 patients, 87 were finally included (Table) and 8 excluded due to the lack of relevant data. Median age was 67 years and 75.9% were men. A total of 64.4% of patients had acute myocardial infarction as risk factor for LVT development while 21.8% and 5.7% of patients had dilated and primary hypertrophic cardiomyopathy, respectively. A reduced EF and atrial fibrillation were present in 77.0% and 19.5% of patients, respectively. All but one patient received warfarin with a median TTR of 54%, and 35.5% of patients did not receive concomitant antiplatelet therapy. All included patients received VKAs for at least 12-months. The 3 and 12 month cumulative incidences (Figure) of thrombus resolution were 34.5% (95% CI, 24.7%-44.5%) and 68.3% (95% CI, 57.2%-77.1%), respectively. At multivariable Cox regression analysis, the presence of a reduced EF appeared to be associated with a higher risk of thrombus persistence at 12-months follow-up (Hazard Ratio 3.09; 95% CI 1.27-7.55; p=0.013). During 12-months follow-up, two patients (2.3%) had acute ischemic stroke at 4 and 7 months from the start of VKAs therapy. Three patients (3.4%) had a major and 5 (5.7%) a clinically relevant non-major bleeding that occurred within the first three months of VKAs. Conclusions A 12-month course of anticoagulant therapy with VKA appeared to be effective and safe in patients with LVT and appeared to be associated with a higher cumulative incidence of LVT resolution than a 3-month course. A reduced left ventricular EF was associated with a higher risk of LVT persistence. Whether anticoagulant agents with improved ease-of-use and safety profile are effective in this setting remains undefined.Baseline patients' characteristicsCumulative incidences of LVT resolution

P1695: CEREBRAL VENOUS THROMBOSIS AND ANTITHROMBOTIC THERAPY: A SYSTEMATIC REVIEW

Background: Cerebral venous thrombosis (CVT) is a cause of stroke especially in the young. The anticoagulant treatment remains controversial as it prevents neurological deterioration, new venous infarcts and death but there is a risk of bleeding complications Aims: The aim of the study was to systematically review the available studies on the efficacy and safety of anticoagulant therapy in CVT Methods: A literature search was performed (PubMed) by a combination of the terms: 1. cerebral vein thrombosis 2. cerebral venous thrombosis 3. antithrombotic therapy 4. anticoagulant therapy 5. heparin 6. warfarin 7. VKA 8. DOAC. The references of the studies were checked to obtain additional studies. The search included studies: a) related to humans b) in English and c) period:1991-2021. The following data were extracted: study characteristics (year of publication, country, study-type, sample size), demographic characteristics, type/dose of anticoagulant therapy, median follow-up, major bleeding complications, other complications during follow-up. The inclusion criteria were: 1) CVT confirmed by imaging (angiography,CT,MRI,MRV) 2) any type of anticoagulation 3) sample size>5 & 4) age>16 years Results: 25 studies were included with a total number of 2320 patients. The percentage of female patients was 70%. The age ranged 16-86 years. A total of 6 RCT, 9 prospective observational studies, 9 retrospective observational studies and 1 ambidirectional observational study were detected. Based on the limited data the anticoagulant therapy appears safe and effective, as in the acute phase it improves the clinical outcome. It is recommended that patients with acute CVT are treated with heparin. It is not contraindicated even in hemorrhagic infarcts but should be used with caution in extensive hemorrhagic infarcts, in-depth localization of the infarct and coma. LMWH appears to be associated with better outcome and fewer new intracranial hemorrhages than UFH. There is no study evaluating the role of antiplatelets. There are also insufficient data on the optimal duration of anticoagulation therapy. The use of DOAC is not recommended for the treatment of CVT, especially in the acute phase, due to the poor available evidence. Nevertheless, the limited data on the use of DOAC in the treatment of CVT imply adequate safety and efficacy. There is no study comparing different DOAC for CVT treatment. There are also insufficient data to support the use of thrombolysis in patients with CVT, as only case-reports and patient-series have been published. There is only 1 RCT in which “high-risk” patients were randomized to intravascular thrombolysis or heparin-controlled treatment. According to the European Guideline for the diagnosis and management of CVT it is not possible to provide recommendation for thrombolysis. It is suggested though not to use thrombolysis in patients with acute CVT with a low risk of poor outcome. The present systematic review highlights the lack of adequate data on optimal anticoagulation therapy in CVT Summary/Conclusion: Anticoagulant therapy for CVT appears to be safe and effective. It is recommended that patients with acute CVT are treated with heparin even cases with bleeding elements at diagnosis. LMWH appears to be associated with better outcomes and fewer new intracranial hemorrhages. The position of DOACs is an object of future research. Thrombolysis in CVT should be reserved for high-risk patients. Given the low incidence of the disease the cooperation of centers at international level is necessary. The subject of anticoagulant therapy in the treatment of CVT remains open for further research

Risk of stroke even after dissipation of a thrombus in the pulmonary vein stump after lobectomy: A case report.

Introduction and importanceThrombosis in the pulmonary vein stump (PVS) after lung resection has been reported as a cause of cerebral infarction (CI). However, there is limited research focusing on thrombosis in the PVS. Although anticoagulant therapy is performed in clinical settings, the optimal duration of anticoagulant therapy is not established. In addition, no case leading to CI after withdrawal of the anticoagulant therapy has been reported.Case presentationAn 81-year-old woman with lung cancer underwent left lower lobectomy. Since a thrombus was detected in the PVS 6 months after the operation, anticoagulant therapy was started. The thrombus disappeared 1 month later, and the medication was discontinued. However, only 23 days after discontinuation, the patient developed CI.Clinical discussionThis case was considered as cardiogenic CI due to a thrombus in the PVS because of the presence of the past thrombus, the distribution of infarction, and the absence of atrial fibrillation. The length of PVS in this case was longer than that reported previously, which could have caused turbulence and congestion leading to thrombogenesis. As long as patients have a long neck PVS, there might be a potential risk of thrombosis.ConclusionWe must recognize the risks associated with the discontinuation of anticoagulant therapy for thrombosis in PVS even after thrombus dissipation.

The Association between Anticoagulation Duration and the Risk of Venous Thromboembolism in Patients with Lower Limb Superficial Vein Thrombosis: A Systematic Review and Meta-analysis

Systemic anticoagulation is the first-line treatment of extensive superficial vein thrombosis (SVT) to reduce the incidence of further venous thromboembolism (VTE). However, the optimal duration of anticoagulant therapy (ACT) is not established. Here we estimate the VTE rates among patients with lower limb SVT according to the duration of anticoagulation.

Effect of Anticoagulant Therapy for 6 Weeks vs 3 Months on Recurrence and Bleeding Events in Patients Younger Than 21 Years of Age With Provoked Venous Thromboembolism

Among patients younger than 21 years of age, the optimal duration of anticoagulant therapy for venous thromboembolism is unknown. To test the hypothesis that a 6-week duration of anticoagulant therapy for provoked venous thromboembolism is noninferior to a conventional 3-month therapy duration in patients younger than 21 years of age. Randomized clinical trial involving 417 patients younger than 21 years of age with acute, provoked venous thromboembolism enrolled at 42 centers in 5 countries from 2008-2021. The main exclusions were severe anticoagulant deficiencies or prior venous thromboembolism. Patients without persistent antiphospholipid antibodies and whose thrombi were resolved or not completely occlusive upon repeat imaging at 6 weeks after diagnosis underwent randomization. The final visit for the primary end points occurred in January 2021. Total duration for anticoagulant therapy of 6 weeks (n = 207) vs 3 months (n = 210) for provoked venous thromboembolism. The primary efficacy and safety end points were centrally adjudicated symptomatic recurrent venous thromboembolism and clinically relevant bleeding events within 1 year blinded to treatment group. The primary analysis was noninferiority in the per-protocol population. The noninferiority boundary incorporated a bivariate trade-off that included an absolute increase of 0% in symptomatic recurrent venous thromboembolism with an absolute risk reduction of 4% in clinically relevant bleeding events (1 of 3 points on the bivariate noninferiority boundary curve). Among 417 randomized patients, 297 (median age, 8.3 [range, 0.04-20.9] years; 49% female) met criteria for the primary per-protocol population analysis. The Kaplan-Meier estimate for the 1-year cumulative incidence of the primary efficacy outcome was 0.66% (95% CI, 0%-1.95%) in the 6-week anticoagulant therapy group and 0.70% (95% CI, 0%-2.07%) in the 3-month anticoagulant therapy group, and for the primary safety outcome, the incidence was 0.65% (95% CI, 0%-1.91%) and 0.70% (95% CI, 0%-2.06%). Based on absolute risk differences in recurrent venous thromboembolism and clinically relevant bleeding events between groups, noninferiority was demonstrated. Adverse events occurred in 26% of patients in the 6-week anticoagulant therapy group and in 32% of patients in the 3-month anticoagulant therapy group; the most common adverse event was fever (1.9% and 3.4%, respectively). Among patients younger than 21 years of age with provoked venous thromboembolism, anticoagulant therapy for 6 weeks compared with 3 months met noninferiority criteria based on the trade-off between recurrent venous thromboembolism risk and bleeding risk. ClinicalTrials.gov Identifier: NCT00687882.

D-dimer - uloga u hemostaznom sistemu i primena u specifičnim kliničkim stanjima

D-dimer is a soluble fibrin degradation product, which is formed by the breakdown of cross-linked fibrin monomers, previously created under thrombin activity, formed as a result of hemostatic activation. The degradation of cross-linked fibrin occurs as part of the activation of the fibrinolysis system, whose task is to remove the created coagulum and ensure the patency of the blood vessel. This process takes place under the influence of the most important fibrinolytic enzyme, plasmin. D-dimer can, therefore be considered a biomarker of coagulation activation and fibrinolysis, and is routinely used to rule out venous thromboembolism (VTE). D-dimer is increasingly used to assess the risk of VTE recurrence and to help define the optimal duration of anticoagulant therapy in the treatment of patients with VTE, to diagnose disseminated intravascular coagulation (DIC), to screen medical patients at increased risk of VTE. In particular, the use of D-dimer, which is sometimes unjustifiably high, should be emphasized, as part of the monitoring and treatment of patients with COVID-19 infection. This review article aims to: (1) define the origin and role of D-dimer in the hemostatic system, (2) the method of performing the analysis, the selection of adequate tests and interpretation in accordance with the consideration of possible preanalytical variables that affect the measurement of D-dimer; (3) consideration of its application in specific clinical settings or diseases.

Risk factors of recurrence and major bleeding in patients with intermediate-risk for recurrence of venous thromboembolism: from the COMMAND VTE Registry

Abstract Background/Introduction Patients with venous thromboembolism (VTE), including pulmonary embolism (PE), have a long-term risk of recurrence, and anticoagulation therapy is recommended for the prevention of recurrence. The latest 2019 European Society of Cardiology (ESC) guideline classified the risks of recurrence into low- (<3%/year), intermediate- (3–8%/year), and high- (>8%/year) risk, and recommended the extended anticoagulation therapy of indefinite duration for high-risk patients as well as intermediate-risk patients. However, extended anticoagulation therapy of indefinite duration for all of intermediate-risk patients have been a matter of active debate. Thus, additional risk assessment of recurrence in intermediate-risk patients might be clinically relevant in defining the optimal duration of anticoagulation therapy. Furthermore, bleeding risk during anticoagulation therapy should also be taken into consideration for optimal duration of anticoagulation therapy. However, there are limited data assessing the risk of recurrence as well as bleeding in patients with intermediate-risk for recurrence based on the classification in the latest 2019 ESC guideline. Purpose The current study aimed to identify the risk factors of recurrence as well as major bleeding in patients with intermediate-risk for recurrence, using a large observational database of VTE patients in Japan. Methods The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1703 patients with intermediate-risk for recurrence. The primary outcome measure was recurrent VTE during the entire follow-up period, and the secondary outcome measures were recurrent VTE and major bleeding during anticoagulation therapy. Results In the multivariable Cox regression model for recurrent VTE incorporating the status of anticoagulation therapy as a time-updated covariate, off-anticoagulation therapy was strongly associated with an increased risk for recurrent VTE (HR 9.42, 95% CI 5.97–14.86). During anticoagulation therapy, the independent risk factor for recurrent VTE was thrombophilia (HR 3.58, 95% CI 1.56–7.50), while the independent risk factors for major bleeding were age ≥75 years (HR 2.04, 95% CI 1.36–3.07), men (HR 1.52, 95% CI 1.02–2.27), history of major bleeding (HR 3.48, 95% CI 1.82–6.14) and thrombocytopenia (HR 3.73, 95% CI 2.04–6.37). Conclusions Among VTE patients with intermediate-risk for recurrence, discontinuation of anticoagulation therapy was a very strong independent risk factor of recurrence during the entire follow-up period. The independent risk factors of recurrent VTE and those of major bleeding during anticoagulation therapy were different: thrombophilia for recurrent VTE, and advanced age, men, history of major bleeding, and thrombocytopenia for major bleeding. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation

A Decision Model to Estimate Risk Thresholds for Guiding Duration of Anticaogulation in Unprovoked Venous Thromboembolism

▪Background: For patients with a first unprovoked venous thromboembolism (VTE), the optimal duration of anticoagulant therapy (AT) is a crucial clinical dilemma which has yet to be resolved . Choosing short-term (3-6 months) or indefinite AT, requires balancing the long-term risk of recurrent VTE when AT is discontinued, with the long-term risk of major bleeding (MB) from extended AT. Current guidelines suggest considering indefinite AT in all unprovoked VTE patients with non-high bleeding risk. This however, is a weak-evidence recommendation based on limited data, and no precise risk thresholds have been established to help guide treatment duration in this patient population. From an economic perspective, we aimed to identify thresholds of the risk of MB and recurrent VTE for which indefinite AT, as compared to stopping AT after initial short-term treatment, may be warranted.Methods: We constructed a Markov decision model of patients with a first unprovoked VTE who had completed at least 3-6 months of initial AT. The model adopted a lifetime horizon and a publicly-funded healthcare system perspective. Using a cycle length of one year, the model tracked recurrent VTE (DVT and/or PE), MB, and death from any cause [Figure 1]. For the base case, we considered patients aged 57 years, having a life expectancy of 30 years, annual risk of MB on Vitamin K Antagonists of 1.5%, annual recurrent VTE risk of 5% per year off therapy, case-fatality-rate (CFR) for MB of 11.3%, and CFR for recurrent VTE of 3.6%. We expressed our results as Incremental Net Benefit (INB) which incorporates costs, life-expectancy, quality-adjusted life-years (QALYs), and a willingness to pay (WTP) value. INB is the incremental benefit, expressed in monetary terms ($), of offering a patient treatment (indefinite AT) rather than the comparator (stopping AT). An INB > 0 favours the treatment, whereas an INB < 0 favours the comparator.Results: For the base case analysis with assuming a decision-maker's WTP threshold of $50,000/QALY, indefinite AT was not justified (i.e. INB < 0) when the annual risk of recurrent VTE off therapy was less than 7.1% [Figure 2], or when the annual risk of MB exceeded 2.4% [Figure 3]. Furthermore, in a two-way sensitivity analysis [Figure 4], as the MB risk increased, so did the recurrent VTE risk threshold for which indefinite AT would be warranted. As illustrated through three hypothetical situations outlined in Figure 4; for a patient with an annual MB risk of 3.5% [scenario A], a recurrence risk of >15% would be required for indefinite AT to be favorable (i.e. INB > 0). Similarly, using a base case annual MB risk of 1.5% [scenario B], from an economic standpoint, the decision to offer indefinite AT would not be preferred for a patient in whom the risk of recurrence is 3%, but may be supported for a patient in whom the risk of recurrence is 10%. Lastly, for a patient with an annual recurrent VTE risk of < 1% [scenario C], continuing AT indefinitely would never be justified, irrespective of the risk of MB.Conclusions/Implications: To the best of our knowledge, this is the first decision analysis of a hypothetical cohort of unprovoked VTE patients that identifies risk thresholds of MB and recurrent VTE to guide treatment duration. From an economic viewpoint, our analysis demonstrates that choosing indefinite AT in such patients may not be justified at the proposed risk thresholds. Furthermore, long-term follow up demonstrates that VTE recurs in less than 50% of such patients after stopping AT;thus, considering indefinite AT in all unprovoked VTE patients is an inefficient use of resources, and exposes a large proportion of patients to the unnecessary risks, burdens and costs of lifelong AT. Establishing risk thresholds, as achieved through our decision model, allows individualized treatment and helps guide patient-centered decision making. If validated and further optimized (as planned prior to the ASH), findings from our study could change clinical practice. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

INFLUENCE OF SEX ON LONG-TERM RISK OF MAJOR BLEEDING DURING EXTENDED ORAL ANTICOAGULANT THERAPY FOR UNPROVOKED VENOUS THROMBOEMBOLISM: A SYSTEMATIC REVIEW AND META-ANALYSIS

Venous thromboembolism (VTE) is a leading cause of cardiovascular death. The optimal duration of anticoagulant therapy for a first unprovoked VTE is uncertain. Deciding whether to continue anticoagulation indefinitely after completing at least 3 months of initial treatment, requires balancing the long-term risk of recurrent VTE if anticoagulation is discontinued with the long-term risk of major bleeding if anticoagulation is continued. We previously showed that men with a first unprovoked VTE have a higher long-term risk of recurrent VTE than women (Khan F et al., BMJ 2019).

Validation of the VTE‐BLEED score’s long‐term performance for major bleeding in patients with venous thromboembolisms: From the COMMAND VTE registry

BackgroundThe recently proposed VTE‐BLEED score to predict the risk of major bleeding in patients with venous thromboembolisms (VTEs) on prolonged anticoagulation therapy was validated externally in randomized controlled trials and in a selected cohort, but not applied in non‐selective cohorts. ObjectivesThe present study aimed to evaluate the generalizability of the VTE‐BLEED score in a non‐selective cohort. Patients/MethodsThe COMMAND VTE Registry is a multicenter retrospective registry enrolling consecutive patients with acute symptomatic VTEs among 29 centers in Japan. The present study population consisted of 2124 patients with prolonged anticoagulation therapy beyond 30 days, including 2008 (95%) patients with a first VTE episode and 1075 (51%) with unprovoked VTEs, who were divided into 1445 patients (68%) with a VTE‐BLEED score of ≥2 (high‐risk group) and 679 (32%) with a VTE‐BLEED score of <2 (low‐risk group). ResultsDuring a median follow‐up period of 672 days, major bleeding events occurred in 121 patients. The cumulative 5‐year incidence of major bleeding beyond 30 days was significantly higher in the high‐risk group than low‐risk group (13.2% versus 5.4%, P < .001). The hazard function curves demonstrated that the hazards of the high‐risk group were consistently higher over time compared with the low‐risk group, which suggested the long‐term predictive ability of the score. ConclusionsIn the present real‐world VTE registry, the VTE‐BLEED score had a long‐term predictive ability for high‐risk patients with major bleeding during prolonged anticoagulation therapy, which could be useful in determining the optimal duration of anticoagulation therapy in individual patients.

Role of D-dimer in guiding duration of anticoagulant therapy in the management of first unprovoked proximal lower limb deep venous thrombosis

Background The optimal duration of anticoagulant therapy in management of patients with first episode of unprovoked deep venous thrombosis is uncertain. D-dimer test may play a role in the assessment of duration of anticoagulant therapy to decrease the rate of recurrence. Aim To evaluate if D dimer test can be used as predictor to guide the duration of anticoagulation in patients with first unprovoked proximal lower limb deep venous thrombosis. Patients and Methods One hundred patients with a first unprovoked proximal deep-vein thrombosis who completed 3 months of Vitamin K Antagonists (VKAs) and had elevated d dimer test 1 month after discontinuation of anticoagulation were randomly assigned either to resume (group A) or to discontinue treatment (group B). The patients were followed up for 1 year for recurrent venous thromboembolism and treatment complications. Results The mean age of the patients was 49.96±7.88 and 51.78±7.98 years for group A and B respectively. Male to female ratio was nearly similar in both groups 3:2 . The base line D-dimer level was 3.05±0.84 and 3.15±1.00 for group A and B respectively with no statistical significant difference. The mean duration of follow up was 10.6 months for both groups. The recurrence rate was higher in group B (7 cases) compared to group A (1 case) (P value 0.027) and this difference was statistically significant. No major bleeding or pulmonary embolism have been noticed in any patients during follow up. Conclusion Elevated D dimer test 1 month after discontinuation of 3 months anticoagulation, in the absence of recent thrombosis, could be an indicator for resumption of anticoagulant therapy for another 3 months.

P2773Evaluation of the bleeding prediction score VTE-BLEED for predicting recurrent VTE

Abstract Introduction VTE-BLEED is a validated score for identification of patients at a 3 to 5-fold increased risk of major bleeding during extended anticoagulation for venous thromboembolism (VTE; table 1). It is unknown whether VTE-BLEED high-risk patients also have an increased risk for recurrent VTE, which would limit the potential usefulness of the score. Methods This was a post-hoc analysis of the randomised double-blind placebo-controlled PADIS-PE trial, in which patients with a first unprovoked pulmonary embolism (PE) initially treated for 6 months were randomised to receive an additional 18-month of warfarin versus placebo. Primary outcome of the current analysis was recurrent VTE during 2-year follow-up after anticoagulant discontinuation, i.e. after the initial 6-month treatment in the placebo arm and after 24 months of anticoagulation in the active treatment arm. This rate, adjusted on study treatment allocation, was compared between patients in the high- versus low-risk VTE-BLEED group. Results In complete case analysis (n=308; 82.4% of total population), 89 (28.9%) patients were classified as VTE-BLEED high risk. A total of 44 VTE events occurred after anticoagulant discontinuation during 668 patient-years. The cumulative incidence of recurrent VTE was 16.4% (95% CI 10.0–26.1%; 14 events) and 14.6% (95% CI 10.4–20.3%; 30 events) in the high-risk and low-risk VTE-BLEED groups, respectively, for an adjusted Hazard Ratio of 1.16 (95% CI 0.62–2.19; Figure 1). Figure 1 Conclusion In this study, patients with unprovoked PE classified at high risk of major bleeding by VTE-BLEED did not have a higher incidence of recurrent VTE after cessation of anticoagulant therapy, supporting the potential yield of the score for making management decisions on the optimal duration of anticoagulant therapy.

Evaluation of the predictive value of the bleeding prediction score VTE‐BLEED for recurrent venous thromboembolism

IntroductionVTE‐BLEED is a validated score for identification of patients at increased risk of major bleeding during extended anticoagulation for venous thromboembolism (VTE). It is unknown whether VTE‐BLEED high‐risk patients also have an increased risk for recurrent VTE, which would limit the potential usefulness of the score. MethodsThis was a post hoc analysis of the randomized, double‐blind, placebo‐controlled PADIS‐PE trial that randomized patients with a first unprovoked pulmonary embolism (PE) initially treated during 6 months to receive an additional 18‐month of warfarin vs. placebo. The primary outcome of this analysis was recurrent VTE during 2‐year follow‐up after anticoagulant discontinuation, that is, after the initial 6‐month treatment in the placebo arm and after 24 months of anticoagulation in the active treatment arm. This rate, adjusted for study treatment allocation, was compared between patients in the high‐ vs. low‐risk VTE‐BLEED group. ResultsIn complete case analysis (n = 308; 82.4% of total population), 89 (28.9%) patients were classified as high risk; 44 VTE events occurred after anticoagulant discontinuation during 668 patient‐years. The cumulative incidence of recurrent VTE was 16.4% (95% confidence interval [CI], 10.0%‐26.1%; 14 events) and 14.6% (95% CI, 10.4%‐20.3%; 30 events) in the high‐risk and low‐risk VTE‐BLEED groups, respectively, for an adjusted hazard ratio of 1.16 (95% CI, 0.62‐2.19). ConclusionIn this study, patients with unprovoked PE classified at high risk of major bleeding by VTE‐BLEED did not have a higher incidence of recurrent VTE after cessation of anticoagulant therapy, supporting the potential yield of the score for making management decisions on the optimal duration of anticoagulant therapy.

Optimal Duration of Anticoagulation Therapy for Isolated Distal Deep Vein Thrombosis in Patients With Cancer Study

Optimal Duration of Anticoagulation Therapy for Isolated Distal Deep Vein Thrombosis in Patients With Cancer Study

Cessation of anticoagulation therapy following endovascular thrombus removal and stent placement for acute iliofemoral deep vein thrombosis.

Background: The optimal duration of anticoagulation therapy (AT) following catheter-based therapy of acute iliofemoral deep vein thrombosis (IFDVT) with stent placement is unknown. Theoretically, resolving the underlying obstructive iliac vein lesion by a stent may eliminate the main trigger for recurrence, the post-thrombotic syndrome (PTS), and the need for extended-duration AT. Patients and methods: From 113 patients with acute IFDVT who underwent endovascular thrombus removal and stent placement, we compared patency rates and clinical outcomes between 58 patients on limited-duration AT (3-12 month) and 55 patients on extended-duration AT (>12 months). Results: Mean follow-up duration was 26±18 (range 3-77) months; it was 24±18 (range 3-69) months after cessation of AT in the limited-duration AT group. In comparison to patients with extended-duration AT, patients with limited-duration AT were younger (38 versus 54 years; p<0.001), more often female (74% versus 49%; p=0.01), and had less often prior venous thromboembolism (VTE) (9% versus 35%; p=0.001). May-Thurner syndrome was more frequent in the limited-duration AT group (66% versus 38%; p=0.004). Overall, primary and secondary patency rates at 24 months were 80% (95% CI, 70-87%) and 95% (95% CI, 88-98%), respectively, with no difference between the groups. Overall, 17 (15%) patients developed recurrent VTE, of which 14 (82%) events were thrombotic stent occlusions, and 13 (76%) events occurred during AT. In the limited-duration AT group, 98% patients were free from the PTS at two years with a VTE recurrence rate of 3.5 per 100 patient years after cessation of AT. Conclusions: In selected patients with acute IFDVT and patent venous stent, particularly in younger and otherwise healthy patients with May-Thurner syndrome, it appears to be safe to discontinue AT 3-12 months after endovascular treatment. Clinical Trial Registration: The study is registered on the National Institutes of Health website (ClinicalTrials.gov; identifier NCT02433054).

Contemporary approaches to determine the duration of anticoagulant therapy for venous thromboembolism

The review is devoted to the issue of optimal duration of anticoagulant therapy for venous thromboembolic complications (VTEC) using oral anticoagulants (OAC). These drugs are characterized by higher safety in comparison with vitamin K antagonists and make it possible to increase the duration of treatment for not only spontaneous thrombosis (with high risk of recurrence), but also thrombosis provoked by minor persistent and transient risk factors of VTEC. Efficacy and safety of prolonged treatment of VTEC using OAC was analyzed. Different classifications of primary thrombotic episode depending on risk of subsequent recurrence are presented. Moreover, scales for individual assessment of risk of recurrent thrombosis after anticoagulant therapy cancellation and risk of bleeding in case of continued treatment are given. Outcomes of long-term administration of rivaroxaban for VTEC are analyzed. It was concluded that OAC are safe for prolonged management of primary thrombotic episode. However, overall duration of treatment should be determined considering individual balance of benefits and risks.

Risk-Stratified Anticoagulation Therapy after First Catheter-Related Venous Thromboembolism in Pediatric Patients

Background: The overall incidence of venous thromboembolism (VTE) has steadily increased in the pediatric population, largely due to rising utilization of central venous catheters (CVCs). Anticoagulation is the mainstay therapy for pediatric CVC-related VTE. Due to paucity of prospective data, optimal duration of anticoagulation therapy has yet to be defined and current recommendations for anticoagulation duration are largely extrapolated from data in adult patients with lower extremity deep vein thrombosis (DVT) and small, non-randomized studies. The objective of this study is to report outcomes of a risk-stratified anticoagulation protocol in a cohort of pediatric patients with CVC-related VTE followed at our center.Methods: We performed a retrospective analysis of a prospectively maintained institutional thrombosis patient registry created using Research Electronic Data Capture (REDCap). We identified all patients with an objectively confirmed catheter-related VTE who were followed at our institution over a 5-year period (2012-2017). Patients were managed according to an institutional risk-stratified protocol in which patients received therapeutic enoxaparin for a maximal duration of 3 months with assessment of radiologic response at 6 weeks and 3 months. After 6 weeks of therapy, enoxaparin was discontinued if the CVC had been removed, or decreased to prophylactic dosing if the CVC is still present in low risk patients with non-recurrent CVC-related DVT who had complete radiologic thrombus resolution and no major thrombophilia. We compared patients with complete resolution at 6 weeks to those who did not have complete resolution at 6 weeks with respect to demographics, relevant clinical characteristics, baseline laboratory measurements, anticoagulation quality measurements, and key outcome measures (frequency of a composite of recurrent symptomatic radiologically-confirmed DVT, pulmonary embolism (PE) and/or paradoxical embolism, frequency of post-thrombotic syndrome (PTS), and frequency of anticoagulation-related major bleeding and/or clinically relevant non-major bleeding). Data was compared using the Mann-Whitney U test or Fisher exact test as appropriate. Two-tailed p value less than 0.05 was considered statistically significant.Results: A total of 137 patients who developed a CVC-related VTE at our institution during the study period were included in the analysis. Of 137 patients, 70 (51%) patients had complete radiologic resolution at 6 weeks, while 26% had partial resolution, 20% had non-resolution and 3% were noted to have radiologic progression. At 3 months, 38% of patients had complete resolution, 24% had partial resolution, 21% had non-resolution and 7% showed radiologic progression. Patients who had complete resolution at 6 weeks were largely similar in their characteristics to those who did not show complete resolution at 6 weeks (Table 1). The frequency of thrombophilia was not different between the two groups and none of the patients were found to have major thrombophilia (Table 1). However, the frequency of vena cava involvement was significantly higher and the time to achieve therapeutic anticoagulation was significantly longer in patients who did not show complete resolution at 6 weeks (Table 1). The frequency of recurrent clinically symptomatic DVT, PE and/or paradoxical embolism in patients with complete radiologic resolution at 6 weeks [5/70 (7%)] was similar to those who did not show complete radiologic resolution at 6 weeks [9/67 (13%)] (p=0.27). The frequency of PTS was significantly higher in patients who did not show complete radiologic resolution at 6 weeks [5/60 (8%)] compared to patients with complete radiologic resolution at 6 weeks [0/64 (0%)] (p=0.02). The frequency of anticoagulation-related bleeding events was similar in patients with complete radiologic resolution at 6 weeks [6/70 (9%)] and patients who did not have complete radiologic resolution at 6 weeks [6/67 (9%)] (p=1.00).Conclusion: Our study suggests that pediatric patients with CVC-related DVT who demonstrate complete radiologic resolution after 6 weeks of anticoagulation represent a lower risk patient group that appears to have favorable outcomes. Vena cava involvement and longer time to achieve therapeutic anticoagulation may be associated with suboptimal radiologic response at 6 weeks. Larger prospective studies are needed to confirm our results. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Residual pulmonary vascular obstruction and recurrence after acute pulmonary embolism: protocol for a systematic review and meta-analysis of individual participant data

BackgroundIn patients with a first, unprovoked venous thromboembolism (VTE), the optimal duration of anticoagulant therapy (AT) is controversial due to tightly balanced risks and benefits of indefinite anticoagulation. The objective...

META-ANALYSIS OF LONG-TERM RISK OF FATAL PULMONARY EMBOLISM AFTER DISCONTINUING ANTICOAGULANT THERAPY FOR FIRST UNPROVOKED VENOUS THROMBOEMBOLISM

Venous thromboembolism (VTE), manifesting itself as deep vein thrombosis and/or pulmonary embolism (PE) is a leading cause of cardiovascular death. The optimal duration of anticoagulant therapy in patients with a first unprovoked VTE is controversial, due to closely balanced risks of mortality from recurrent VTE if anticoagulation is discontinued, and mortality form major bleeding if anticoagulation is continued. As such, when deciding whether to discontinue anticoagulation after completing initial course of treatment, the subsequent risk of fatal PE is an important prognostic consideration. This risk however, is unclear, hindering decision making. We performed a systematic review and meta-analysis of randomized clinical trials and prospective observational studies to establish precise and reliable estimates of the absolute, long-term risk of fatal PE at standardized time intervals of 1, 2, 5, and 10 years after discontinuing anticoagulant therapy, as well the case-fatality rate of recurrent VTE in patients with a first episode of unprovoked VTE, who had completed at least three months of initial anticoagulation. Absolute rate of fatal PE was calculated for each study from the total number of fatal PE events and the corresponding patient-years of follow-up. Case-fatality rate was defined as the proportion of overall recurrent VTE events that were fatal. Study results were pooled using random-effects meta-analyses. Of 896 identified records, data was available and/or obtained from authors of 15 eligible studies involving 6,627 patients. The weighted, pooled absolute rate of fatal PE (per 100 patient-years) after stopping anticoagulation was 0.4 events (95% CI, 0.2-0.7) in the first year; 0.3 events (95% CI, 0.2-0.6) in the second year; and average 0.1 events/year (95% CI, 0.0-0.3) in the subsequent eight years off treatment (i.e. between year 2 and 10) [Table 1], resulting in a cumulative 10-year risk of 1.5% after discontinuing anticoagulant therapy. Based on a total of 1,035 recurrent VTE and 48 fatal PE events, the weighted, pooled case-fatality rate for recurrent VTE after stopping anticoagulation was 4.0% (95% CI, 2.1%-6.3%) [Figure 1]. Unselected patients with a first episode unprovoked VTE have a low long-term risk (<1% per year) of fatal PE after stopping anticoagulation. This information, together with the case-fatality rate of recurrent VTE helps inform patient prognosis, and may assist clinicians when considering the risks of mortality from recurrent VTE and major bleeding to decide whether to stop or continue anticoagulant therapy for unprovoked VTE.View Large Image Figure ViewerDownload Hi-res image Download (PPT)