Recurrent Venous Thromboembolism In Patients Research Articles

Risk of Recurrent Venous Thromboembolism in Patients with Cancer: An Individual Patient Data Meta-analysis and Development of a Prediction Model.

About 7% of patients with cancer-associated venous thromboembolism (CAT) develop a recurrence during anticoagulant treatment. Identification of high-risk patients may help guide treatment decisions. To identify clinical predictors and develop a prediction model for on-treatment recurrent CAT. For this individual patient data meta-analysis, we used data from four randomized controlled trials evaluating low-molecular-weight heparin or direct oral anticoagulants (DOACs) for CAT (Hokusai VTE Cancer, SELECT-D, CLOT, and CATCH). The primary outcome was adjudicated on-treatment recurrent CAT during a 6-month follow-up. A clinical prediction model was developed using multivariable logistic regression analysis with backward selection. This model was validated using internal-external cross-validation. Performance was assessed by the c-statistic and a calibration plot. After excluding patients using vitamin K antagonists, the combined dataset comprised 2,245 patients with cancer and acute CAT who were treated with edoxaban (23%), rivaroxaban (9%), dalteparin (47%), or tinzaparin (20%). Recurrent on-treatment CAT during the 6-month follow-up occurred in 150 (6.7%) patients. Predictors included in the final model were age (restricted cubic spline), breast cancer (odds ratio [OR]: 0.42; 95% confidence interval [CI]: 0.20-0.87), metastatic disease (OR: 1.44; 95% CI: 1.01-2.05), treatment with DOAC (OR: 0.66; 95% CI: 0.44-0.98), and deep vein thrombosis only as an index event (OR: 1.72; 95% CI: 1.31-2.27). The c-statistic of the model was 0.63 (95% CI: 0.54-0.72) after internal-external cross-validation. Calibration varied across studies. The prediction model for recurrent CAT included five clinical predictors and has only modest discrimination. Prediction of recurrent CAT at the initiation of anticoagulation remains challenging.

Effectiveness and Safety of Extended Treatment Apixaban Versus Low-Molecular-Weight Heparin in Cancer-Associated Venous Thromboembolism.

Limited real-world evidence is available comparing the safety and effectiveness of apixaban and low-molecular-weight heparins (LMWHs) for preventing recurrent venous thromboembolism (VTE) in patients with active cancer receiving anticoagulation in an extended treatment setting. This study evaluated the risk of bleeding and recurrent VTE in patients with cancer-associated VTE who were prescribed apixaban or LMWH for ≥3 months. A US commercial claims database was used to identify adult patients with VTE and active cancer who initiated apixaban or LMWH 30 days following the first VTE diagnosis and had ≥3 months of continuous enrollment and 3 months of primary anticoagulation treatment. Patients were followed from the day after the end of primary anticoagulation treatment until the earliest of: date of disenrollment, discontinuation of index anticoagulant, switch to another anticoagulant, or end of the study period. Inverse-probability treatment weighting (IPTW) was used to balance treatment cohorts. Incidence rates (IRs) for the outcomes were calculated per 100 person-years (PY). Cox proportional hazard models were used to evaluate the adjusted risk of recurrent VTE, major bleeding (MB), and clinically relevant nonmajor bleeding (CRNMB). A total of 13,564 apixaban- and 2,808 LMWH-treated patients were analyzed. Post-IPTW, the treatment cohorts were balanced. Patients receiving apixaban had lower adjusted IRs for recurrent VTE (4.1 vs 9.6 per 100 PY), MB (6.3 vs 12.6), and CRNMB (26.1 vs 36.0) versus LMWH (P<.0001 for all comparisons) during the follow-up period. Patients on apixaban had a lower adjusted risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.34-0.53), MB (HR, 0.50; 95% CI, 0.41-0.61), and CRNMB (HR, 0.76; 95% CI, 0.68-0.85) versus LMWH. Extended anticoagulation treatment of ≥3 months with apixaban was associated with lower rates of recurrent VTE, MB, and CRNMB compared with LMWH in adults with cancer-associated VTE.

A retrospective review of recurrent venous thromboembolism in patients with cancer with direct factor Xa inhibitors.

e24136 Background: Venous thromboembolism (VTE) in cancer patients is a significant cause of morbidity and mortality. People with malignancies are at an increased risk of thrombosis compared to the normal population. Regimens that include platinum-based agents and vascular endothelial growth factor (VEGF) inhibitors have a higher risk of thromboembolism1. The recent ASCO 2023 guidelines for VTE prophylaxis and treatment have advised that direct factor Xa inhibitors are a suitable option for initial and long-term treatment for VTE, given patient preference of oral over subcutaneous administration of anti coagulation2. In our retrospective review of a single centre in Western Australia, we have identified twelve patients who have developed thromboembolic events whilst on direct oral anticoagulation. Methods: Electronic patient records were reviewed for oncology patients attending between 2016 and 2023 at a single centre in Western Australia.Diagnosis of VTE and subsequent treatment was confirmed from radiology and medication records. Twelve patients were identified, and data was recorded and analysed. Results: 12 patients were identified with recurrent VTE whilst on direct factor Xa inhibitors. The median age was 59.5 years (range 50-71). The most common associated malignancies were pancreatic, ovarian and lung cancer. Others include breast, vulval, colon and gastroesophageal cancer. Two thirds of patients were metastatic at diagnosis (n = 8). Common sites of thrombosis include the lower limbs at both initial [n = 6] and recurrent [n = 4] presentation. All patients were treated with therapeutic doses of rivaroxaban (n = 8) or apixaban (n = 4) at the time of of initial or recurrent thrombotic event. Median time to initial thrombotic event was 4.5 months from diagnosis compared to recurrent VTE [5 months]. All patients were changed to either LMWH (n = 10) or unfractionated heparin (n = 2). Ten patients [83.3%] did not have further thrombosis post switching to heparin. One patient had recurrent pulmonary emboli on imaging despite heparin administration, and the other had an IVC filter insertion. Conclusions: VTE is a common complication for oncology patients. Given our results, clinicians should be suspicious for recurrent VTE for patients on direct factor Xa inhibitors. There is an argument for enoxaparin or dalteparin to be better options, particularly in those high risk. Whilst patient preference for an oral option is desirable, further investigation is needed to directly compare the differing direct factor Xa inhibitors and the rates of VTE recurrence.

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

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

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

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

Abstract 15165: Clinical Characteristics and Outcome of Venous Thromboembolism in Patients After Surgical Procedure: From the COMMAND VTE Registry-2

Background: Undergoing surgical procedure is a risk factor for venous thromboembolism (VTE). However, the prognosis of VTE in patients after surgical procedure has not been fully evaluated in the Era of direct oral anticoagulant (DOAC). We elucidated the prognosis of VTE in patients who have undergone surgical procedure. Methods: The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. According to the history of surgical procedure within 2 months, we divided the study patients into 2 groups; Surgical group (N=793) and Non-surgical group (N=4404). Clinical outcome including all-cause death and recurrence of VTE was compared between the two groups. Results: There were more women in surgical group than non-surgical group (64% vs. 58%, P&lt;0.01). In addition, surgical group had higher prevalence of active cancer (34% vs. 28%, P&lt;0.01), and lower prevalence of kidney disease (16% vs. 20%, P&lt;0.01) than non-surgical group. The cumulative incidences of all-cause death and recurrent VTE at 2-year were significantly lower in surgical group than non-surgical group (all-cause death: 16.6±1.4% vs. 24.4±0.7%, P&lt;0.01; recurrent VTE: 2.8±0.7% vs. 5.7±0.4%, P&lt;0.01, respectively). In surgical group, Cox regression analysis identified diabetes mellitus as the independent risk factor for recurrence of VTE (hazard ratio 2.90; 95% confidence interval, 1.24-6.74; P=0.01). Conclusion: Patients after surgical procedure had lower mortality and incidence of recurrent VTE than non-surgical group. Diabetes mellitus is the independent risk factor for recurrence of VTE in patients after surgical procedure.

OC 64.5 Risk of On-Treatment Recurrent Venous Thromboembolism in Patients with Active vs Cured Cancer Patients: A Post-Hoc Analysis of Hokusai VTE Cancer

OC 64.5 Risk of On-Treatment Recurrent Venous Thromboembolism in Patients with Active vs Cured Cancer Patients: A Post-Hoc Analysis of Hokusai VTE Cancer

OC 64.4 Prediction of on Treatment Recurrent Venous Thromboembolism in Patients with Cancer: An Individual Patient Data Meta-Analysis of Randomized Controlled Trials

OC 64.4 Prediction of on Treatment Recurrent Venous Thromboembolism in Patients with Cancer: An Individual Patient Data Meta-Analysis of Randomized Controlled Trials

Development of a predictive model of venous thromboembolism recurrence in anticoagulated cancer patients using machine learning

IntroductionPatients with cancer and venous thromboembolism (VTE) show a high risk of VTE recurrence during anticoagulant treatment. This study aimed to develop a predictive model to assess the risk of VTE recurrence within 6 months at the moment of primary VTE diagnosis in these patients. Materials and methodsUsing the EHRead® technology, based on Natural Language Processing (NLP) and machine learning (ML), the unstructured data in electronic health records from 9 Spanish hospitals between 2014 and 2018 were extracted. Both clinically- and ML-driven feature selection were performed to identify predictors for VTE recurrence. Logistic regression (LR), decision tree (DT), and random forest (RF) algorithms were used to train different prediction models, which were subsequently validated in a hold-out data set. ResultsA total of 16,407 anticoagulated cancer patients with diagnosis of VTE were identified (54.4 % male and median age 70). Deep vein thrombosis, pulmonary embolism and metastases were observed in 67.2 %, 26.6 %, and 47.7 % of the patients, respectively. During the study follow-up, 11.4 % of the patients developed a recurrent VTE, being more frequent in patients with lung cancer. Feature selection and model training based on ML identified primary pulmonary embolism, deep vein thrombosis, metastasis, adenocarcinoma, hemoglobin and serum creatinine levels, platelet and leukocyte count, family history of VTE, and patients' age as predictors of VTE recurrence within 6 months of VTE diagnosis. The LR model had an AUC-ROC (95 % CI) of 0.66 (0.61, 0.70), the DT of 0.69 (0.65, 0.72) and the RF of 0.68 (0.63, 0.72). ConclusionsThis is the first ML-based predictive model designed to predict 6-months VTE recurrence in patients with cancer. These results hold great potential to assist clinicians to identify the high-risk patients and improve their clinical management.

Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin and Recurrent VTE in Patients With Cancer

In patients with cancer who have venous thromboembolism (VTE) events, long-term anticoagulation with low-molecular-weight heparin (LMWH) is recommended to prevent recurrent VTE. The effectiveness of a direct oral anticoagulant (DOAC) compared with LMWH for preventing recurrent VTE in patients with cancer is uncertain. To evaluate DOACs, compared with LMWH, for preventing recurrent VTE and for rates of bleeding in patients with cancer following an initial VTE event. Unblinded, comparative effectiveness, noninferiority randomized clinical trial conducted at 67 oncology practices in the US that enrolled 671 patients with cancer (any invasive solid tumor, lymphoma, multiple myeloma, or chronic lymphocytic leukemia) who had a new clinical or radiological diagnosis of VTE. Enrollment occurred from December 2016 to April 2020. Final follow-up was in November 2020. Participants were randomized in a 1:1 ratio to either a DOAC (n = 335) or LMWH (n = 336) and were followed up for 6 months or until death. Physicians and patients selected any DOAC or any LMWH (or fondaparinux) and physicians selected drug doses. The primary outcome was the recurrent VTE rate at 6 months. Noninferiority of anticoagulation with a DOAC vs LMWH was defined by the upper limit of the 1-sided 95% CI for the difference of a DOAC relative to LMWH of less than 3% in the randomized cohort that received at least 1 dose of assigned treatment. The 6 prespecified secondary outcomes included major bleeding, which was assessed using a 2.5% noninferiority margin. Between December 2016 and April 2020, 671 participants were randomized and 638 (95%) completed the trial (median age, 64 years; 353 women [55%]). Among those randomized to a DOAC, 330 received at least 1 dose. Among those randomized to LMWH, 308 received at least 1 dose. Rates of recurrent VTE were 6.1% in the DOAC group and 8.8% in the LMWH group (difference, -2.7%; 1-sided 95% CI, -100% to 0.7%) consistent with the prespecified noninferiority criterion. Of 6 prespecified secondary outcomes, none were statistically significant. Major bleeding occurred in 5.2% of participants in the DOAC group and 5.6% in the LMWH group (difference, -0.4%; 1-sided 95% CI, -100% to 2.5%) and did not meet the noninferiority criterion. Severe adverse events occurred in 33.8% of participants in the DOAC group and 35.1% in the LMWH group. The most common serious adverse events were anemia and death. Among adults with cancer and VTE, DOACs were noninferior to LMWH for preventing recurrent VTE over 6-month follow-up. These findings support use of a DOAC to prevent recurrent VTE in patients with cancer. ClinicalTrials.gov Identifier: NCT02744092.

Identification of prophylaxis and treatment for hospitalized patients associated with venous thromboembolism.

Identification of prophylaxis and treatment for hospitalized patients associated with venous thromboembolism.

Abstract 8: Outcomes And Recurrence Rates Among Patients With Provoked And Cryptogenic Cerebral Venous Thrombosis: Analysis Of The ACTION CVT Study

Introduction: Cerebral venous thrombosis (CVT) is a rare cause of stroke. While the standard treatment is anticoagulation, the type and duration of anticoagulation depend on the underlying etiology. This study aims to identify the characteristics and risk of recurrent venous thromboembolism (VTE) in patients with unprovoked CVT (cryptogenic), transient provoked CVT (peripartum, contraception, infection, trauma) and persistent provoked CVT (cancer, hereditary thrombophilias). Methods: We used the ACTION CVT retrospective database which included consecutive CVT patients in 27 stroke centers in the United States, Europe, and New Zealand from January 2015 to December 2020. Baseline characteristics were compared between the groups using Chi square test, T test or Mann-Whitney-U test, followed by multivariable logistic regression. We used interaction analysis to assess the risk of recurrent venous thromboembolism (VTE). Results: A total of 1025 CVT patients were included in this study; 363 (35.4%) had transient provoking factors, 152 (14.8%) had persistent provoking factors, and 510 (49.8%) had cryptogenic CVT. Patients with transiently provoked CVT were younger (P=0.003) and more likely to be women (P&lt;0.001), and patients with cryptogenic CVT were less likely to have a prior VTE (P&lt;0.001). Compared to patients with transient provoked, there was higher risk of recurrent VTE in patients with persistent provoking factors (HR 2.59, 95% CI 1.29-5.22, P=0.008) and numerically higher recurrent VTE risk in cryptogenic CVT (HR 1.85, 95% CI 0.98-3.51, P=0.059). These associations did not vary by age, sex, or history of VTE status (p-interaction &gt; 0.1 for all). Results were similar in sensitivity analyses excluding those with positive Factor V Leiden or Prothrombin gene mutation as well as in analyses excluding patients with positive antiphospholipid antibody test. Conclusions: In this multicenter study, we found that the risk of recurrent VTE after CVT may vary depending on the underlying etiology with higher rates in patients with cryptogenic CVT and those with persistent provoking factors. Longer anticoagulation duration may be needed in such groups compared to CVT with transient provoking factors.

Obesity as a Risk Factor for Venous Thromboembolism Recurrence: A Systematic Review.

Background and Objectives: Venous thromboembolism (VTE) encompasses Deep Venous Thrombosis (DVT) and Pulmonary Embolism (PE). The duration of anticoagulant therapy following a VTE event partly relies on the risk of recurrent VTE which depends on the clinical setting where VTE occurred and the VTE risk factors present. Obesity is considered a minor risk factor and studies in the literature have provided conflicting results on whether obesity influences the development of recurrences. The aim of the present study is to assess the effect of obesity on VTE recurrence in patients that suffered from a previous VTE event. Materials and Methods: We conducted systematic research for English language studies in Medline, Scopus and ProQuest databases in order to identify publications that assess the risk of VTE recurrence in obesity. Inclusion criteria were: 1. Diagnosis of VTE, 2. Definition of obesity as a body mass index ≥30 kg/m2, 3. Report of the risk of obesity on VTE recurrence, 4. Adult human population. We did not include case reports, review studies or studies that assessed other forms of thrombosis and/or used other definitions of obesity. We used the Newcastle-Ottawa scale to address the quality of the studies. Results: Twenty studies were included in the analysis, of which 11 where prospective cohort studies, 6 were retrospective cohort studies, 1 was a cross-sectional study, and 2 were post-hoc analysis of randomized clinical trials. Obesity was significantly associated with recurrences in 9 studies and in 3 of them the association was significant only in females. Conclusions: There is heterogeneity between the studies both in their design and results, therefore the effect of obesity on VTE recurrence cannot be adequately estimated. Future randomized clinical studies with appropriately selected population are needed in order to streamline the effect of obesity on VTE recurrence.

Unfavorably altered fibrin clot properties are associated with recurrent venous thromboembolism in patients following post‑discharge events.

Unfavorably altered fibrin clot properties are associated with recurrent venous thromboembolism in patients following post‑discharge events.

Characteristics and predictors of venous thrombosis recurrence in patients with cancer and catheter‐related thrombosis

BackgroundCentral venous catheters raise the risk of catheter‐related thrombosis (CRT) in patients with cancer, typically affecting the upper extremity. Management of CRT involves catheter removal and anticoagulation. However, robust evidence is lacking on the optimal timing of anticoagulation relative to catheter removal. ObjectivesOur goal is to provide a better understanding of the factors that increase the risk of recurrent venous thromboembolism (VTE) in these patients. Patients and MethodsWe conducted a retrospective chart review of all consecutive patients with cancer in our hospital affected by CRT between January 1, 2015, and December 31, 2017. We measured recurrence of VTE as thrombosis in any vascular bed or pulmonary embolism, for up to 2 years after diagnosis. Logistic and competing risk regression analyses were used to determine the association between different clinical factors and any VTE recurrence in patients with cancer and CRT. ResultsOf the 257 individuals meeting the inclusion criteria, 80.2% had their catheter removed; of these, 50.5% did not receive anticoagulation before the removal. Patients who did not receive anticoagulation before the removal had increased 3‐month and 1‐year risks of recurrent VTE (odds ratio, 5.07 [95% confidence interval [CI], 1.53–23.18]; and hazard ratio, 3.47 [95% CI, 1.34–9.01]), respectively. ConclusionsOur study supports the use of anticoagulants before catheter removal in patients with CRT. Randomized clinical trials are recommended to establish stronger evidence pertaining to the long‐term risk of VTE recurrence and the effect of catheter reinsertion.

Current Knowledge on Factor V Leiden Mutation as a Risk Factor for Recurrent Venous Thromboembolism: A Systematic Review and Meta-Analysis.

BackgroundThrombophilia screening is widely done in clinical practice, and it is claimed that the extent of venous thromboembolism (VTE) recurrence risk in patients with common defects is still not fully understood.AimWe aimed to summarize data of all observational studies prospectively assessing the association of heterozygous factor V Leiden (FVL) mutation and recurrent VTE in patients with VTE, and to calculate pooled relative risks (RR), overall and in various subgroups.MethodsWe searched MEDLINE and EMBASE databases for cohort studies prospectively assessing VTE recurrence in patients with and without FVL mutation (PROSPERO: CRD42021182800). Data were extracted on cohort and study-level. The methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). RR were calculated overall and in subgroups using a random-effects model.ResultsFrom 31 cohorts, 24 studies were finally included summarizing 13,571 patients. Heterozygous FVL mutation was identified in 2,840 individuals (21%). The methodological quality was estimated to be high in 20 studies (83%). The overall RR was 1.46 (95% CI: 1.31, 1.64), consistent across subgroups.ConclusionsPooling all high-quality epidemiological data, the risk of recurrent VTE was increased by 46% in patients with heterozygous FVL mutation. Against the background of established risk factors, the FVL mutation plays only a marginal role in the risk assessment for recurrent VTE.

Role of anticoagulants in therapy and prevention of recurrent venous thromboembolism in patients with cancer: a meta-analysis of randomized trials with apixaban

Background Venous thromboembolic complications (VTEC) are a major non-oncological cause of death of patients with malignant neoplasm (MNP). This determines the high significance of antithrombotic therapy for the treatment and secondary prevention of VTEC in this population. During recent years, low-molecular weight heparins (LMWH) have been a "gold standard" for the treatment of cancer-associated venous thrombosis (CAVT). In the recent decade, direct oral anticoagulants (DOACs) have become extensively used for the treatment and prevention of VTEC relapse in non-oncological patients and also for primary prevention of VTEC following orthopedic surgery. Taking into account the oral route of administration, the predictable and convenient pharmacokinetic profile, and the absence of need for coagulation monitoring, it seems possible to use DOACs for the treatment and secondary prevention of VTEС in oncological patients. A meta-analysis of 4 randomized clinical trials (RCTs) showed a higher efficacy of DOACs compared to LMWHs, however, with a greater risk of bleedings in CAVT. In two of four studies using apixaban (more than 40% of weight in meta-analysis), no increase in bleedings was noted.Aim The aim of this study was to perform a systematic search for comparative clinical studies with apixaban and to perform a meta-analysis to answer the question on clinical efficacy and safety of apixaban in the treatment and secondary prevention of recurrent VTEC in patients with CAVT.Material and methods The systematic search was performed in three reference databases, Medline (PubMed), Cochrane Library (CENTRAL), and eLibrary. The search was aimed at publications containing results of RCTs using apixaban for the treatment and prevention of VTEC in patients with MNP. A totality of 678 titles was found; 15 articles were selected for detailed studying, and 4 RCTs were included into the final analysis. The meta-analysis was performed according to the criteria of PRISMA guidelines. Relative risk (RR) was used as a measure of the effect. The meta-analysis was performed by the Mantel-Haenszel method using the R software. Statistical heterogeneity was evaluated with the Cochran criterion (I2); heterogeneity was considered significant at I2 ≥50 %, which was a reason for performing a random-effects meta-analysis. For this meta-analysis, the primary outcome measure was new VTECs (symptomatic or detected proximal deep vein thrombosis and/or symptomatic, detected or fatal pulmonary thromboembolism plus symptomatic upper extremity thromboses, celiac veinous thromboses, and cerebral veinous thromboses if they were included into the efficacy endpoint of the primary studies). The primary safety measure was major bleeding according to ISTH criteria. Other variables included major and clinically significant minor bleedings as well as overall death rate.Results During the systematic search, 4 RCTs were selected. The meta-analysis of the treatment and secondary prevention of VTEC in patients with MNP showed that apixaban was more effective than the active control (88% of LMWHs) in prevention of VTEC relapse. The RR was 0.59; 95 % confidence interval (CI): 0.40-0.86 in the absence of statistically significant differences from the control in the risk of major bleedings (statistically non-significant decrease by 21%), the sum of major and clinically significant minor bleedings, and overall death rate.Conclusion According to the results of the meta-analysis, the DOAC apixaban may be a drug of choice for the treatment and prevention of VTEC relapse in patients with MNO.

Annals for Educators - January 2022.

Annals for Educators - January 2022.

Evaluation of Apixaban in Patients With Antiphospholipid Syndrome: A Case Series and Review of Literature.

Several guidelines endorsed the indefinite use warfarin or heparin-containing products for acute venous thromboembolism (VTE) treatment and secondary prevention and discouraged the use of direct oral anticoagulants (DOAC) for patients diagnosed with antiphospholipid syndrome (APS). However, adequate anticoagulation despite warfarin therapy remains a challenge in APS patients. Using DOACs in APS patients is seen in clinical practice, despite the lack of evidence to support their use in this population. In this case series, we aim to evaluate the safety and effectiveness of apixaban use in nine patients with primary or secondary APS at King Abdulaziz Medical City (Riyadh, Saudi Arabia). All patients presented with APS and received apixaban with or without concomitant antiplatelet. Three patients had double positivity, and two patients had triple positivity of antiphospholipid antibodies (aPL). Some patients tolerated apixaban during the follow-up period, but recurrent VTE and stroke were reported in some of them. Bleeding complications were evident in some cases as well. In conclusion, warfarin remains the best choice to prevent VTE recurrence in patients with APS. On the other side, apixaban use in patients with APS may have some safety and effectiveness concerns evidenced by VTE recurrence and bleeding complications. The safety and effectiveness of utilizing apixaban in APS patients need to be assessed in well-controlled randomized trials.

A Review of the Past, Present and Future of Cancer-associated Thrombosis Management.

Venous thromboembolism (VTE) can have a significant impact on the management, quality of life and mortality of patients with cancer. VTE occurs in 5-20% of patients with cancer, and malignancy is associated with up to 25% of all VTE. It is the second leading cause of death in ambulatory patients with cancer who are receiving chemotherapy. Increased rates of cancer-associated thrombosis are attributed to improved patient survival, increased awareness, surgery, antineoplastic treatments and the use of central venous access devices. Many factors influence cancer-associated thrombosis risk and are broadly categorized into patient-related, cancer-related and treatment-related risks. Direct-acting oral anticoagulants have shown themselves to be at least as effective in preventing recurrent VTE in patients with cancer with symptomatic and incidental VTE. This has led to a change in treatment paradigms so that direct-acting oral anticoagulants are now considered first-line agents in appropriately selected patients. In this article, we review the prior and recent landmark studies that have directed the treatment of cancer-associated thrombosis, and discuss specific factors that affect management as well as future treatment considerations.