Direct Oral Anticoagulants For Venous Thromboembolism Research Articles

Practical guidance for direct oral anticoagulant use in the treatment of venous thromboembolism in primary and metastatic brain tumor patients.

Management of venous thromboembolism (VTE) in patients with primary and metastatic brain tumors (BT) is challenging because of the risk of intracranial hemorrhage (ICH). There are no prospective clinical trials evaluating safety and efficacy of direct oral anticoagulants (DOACs), specifically in patients with BT, but they are widely used for VTE in this population. A group of neuro-oncology experts convened to provide practical clinical guidance for the off-label use of DOACs in treating VTE in patients with BT. We searched PubMed for the following terms: BTs, glioma, glioblastoma (GBM), brain metastasis, VTE, heparin, low-molecular-weight heparin (LWMH), DOACs, and ICH. Although prospective clinical trials are needed, the recommendations presented aim to assist clinicians in making informed decisions regarding DOACs for VTE in patients with BT.

All-Cause Mortality after Major Gastrointestinal Bleeding Among Patients Receiving Direct Oral Anticoagulants: A Systematic Review and Meta-Analysis

Background: Bleeding is the major complication of anticoagulant use, including direct oral anticoagulants (DOACs). Although major gastrointestinal (GI) bleeding represents the single most frequent site of anticoagulant-related bleeding, outcomes after major GI bleeding including mortality are not well characterized and, as a result, severity may be underappreciated with resulting implications for clinical practice. We conducted a systematic review and meta-analysis to quantify the risk for 30-day all-cause mortality after major GI bleeding among DOAC treated patients. Methods: The systematic review protocol was registered with PROSPERO (CRD42022295815). We searched MEDLINE, EMBASE, and Cochrane CENTRAL from inception to November 26 th, 2021 for studies that met the following inclusion criteria: (i) were randomized controlled trials, or prospective and retrospective cohort studies, (ii) included adults treated with a DOAC for venous thromboembolism (VTE) or atrial fibrillation; and (iii) reported 30-day all-cause mortality after major GI bleeding. Two reviewers independently performed study screening and data extraction in duplicate. Summary estimates for 30-day all-cause mortality were calculated using the random-effects inverse-variance method. Statistical heterogeneity was evaluated using the I 2 statistic and by providing 95% prediction intervals. In a sensitivity analysis, we included only studies that defined major GI bleeding based on the International Society on Thrombosis and Haemostasis (ISTH) criteria. Subgroup analyses were performed according to indication for anticoagulation and type of DOAC. Risk of bias was assessed using a modified version of the QUIPS tool for prognostic studies. Results: Of 6548 unique studies identified in our search, we included 17 studies which comprised a total of 3910 DOAC-treated patients with major GI bleeds. The pooled estimate of 30-day mortality after a major GI bleed was 9% (95% CI, 7-13%; I 2=76%) (Figure). In a sensitivity analysis, limited to 15 studies (1846 major GI bleeds) that used the ISTH major GI bleeding definition, the pooled estimate of 30-day mortality was 9% (95% CI, 6-13%; I 2=75%; 95% prediction interval, 2-29%). Studies deemed to be at high risk of bias (5 studies, 228 major GI bleeds) had higher mortality (14%; 95% CI, 8-24%; I 2=8%) than those at low risk of bias (11 studies, 3644 major GI bleeds) where mortality was 8% (95% CI, 6-12%; I 2=81%). In patients receiving a DOAC for either VTE or atrial fibrillation (14 studies, 2764 major GI bleeds), the pooled estimate of 30-day mortality was 11% (95% CI, 7-16%; I 2=10%), and in those receiving a DOAC for atrial fibrillation (3 studies, 1119 major GI bleeds), it was 5% (95% CI, 2-14%; I 2=84%). The pooled estimate of 30-day mortality was 9% (95% CI, 6-14%; I 2=80%) in patients on any DOAC (15 studies, 3747 major GI bleeds), 13% (95% CI, 8-20%; I 2=0%) among those on dabigatran (2 studies, 125 major GI bleeds), and 3% (95% CI, 0-13%) among those rivaroxaban (only 1 study, 38 major GI bleeds). Conclusion: DOAC related major GI bleeding is associated with a significant risk of 30-day mortality. We found substantial heterogeneity across studies which limits the certainty of summary estimates and the ability to compare between DOACs and indications for treatment. Studies reporting on anticoagulation usage should more report on outcomes such as all-cause mortality after bleeding events to better characterize the potential harms of therapy.

Pharmacokinetics and Dosing Regimens of Direct Oral Anticoagulants in Morbidly Obese Patients: An Updated Literature Review.

Data on the impact of morbid obesity (body mass index [BMI] ≥ 40 kg/m2) on the pharmacokinetics (PK), pharmacodynamics (PD) of direct oral anticoagulants (DOACs) are relatively limited, making it difficult to design optimal dosing regimens in morbidly obese patients.To review literature on PK/PD profile, efficacy, and safety of DOACs in venous thromboembolism (VTE) and nonvalvular atrial fibrillation (AF) patients with morbid obesity and make recommendations regarding optimal dosing regimens in these patient populations.A detailed literature search was conducted (from inception to June 22, 2022) for relevant articles involving PK/PD and clinical data on DOACs use in morbidly obese patients with VTE or AF, or healthy volunteers.A total of 28 studies were identified. DOAC-specific PK variations and clinical outcomes have been observed. Obesity may have a modest effect on PK/PD of dabigatran, apixaban, or rivaroxaban. Dabigatran was effective in AF patients with morbid obesity but might increase the risk of gastrointestinal bleeding. Standard dosing of apixaban or rivaroxaban is effective and safe for VTE and AF patients with morbid obesity. Trough edoxaban concentration and anti-Xa activity were similar in different BMI groups (18.5 to >40 kg/m2), and standard dosing of edoxaban may be effective and safe for AF patients.Current evidence suggests dabigatran should be used with caution in patients with AF as it might increase the risk of gastrointestinal bleeding; Standard dosing of apixaban or rivaroxaban can be used in VTE or AF patients; Standard dosing of edoxaban may be considered in AF patients.

Achieving Therapeutic Anti-Xa Levels Using Rivaroxaban for Venous Thromboembolism in a Morbidly Obese Patient with a BMI >70

Background: Anticoagulation (AC) is the cornerstone of treatment for venous thromboembolism (VTE). Direct oral anticoagulants (DOACs) have become the standard of care during the acute and extended phases of therapy for VTE, mostly due to their ease of use, efficacy, and safety profiles. There is a 9.2% prevalence of severe obesity (BMI>40) in Americans as of 2017-2020 with a 6.2-fold increased risk of VTE in obese individuals. The 2021 International Society on Thrombosis and Haemostasis (ISTH) guidelines recommend using standard dosages of DOACs in patients with a BMI >40 kg/m2 or weight >120 kg. Despite these recommendations, their use in severely obese individuals at extremes of weight like our patient with a BMI > 70 kg/m2 remains uncertain. Case Presentation Herein, we present a 38-year-old morbidly obese female with no significant past medical history who presented with an acute worsening of dyspnea on exertion saturating 60% on room air. The diagnosis of intermediate-high risk pulmonary embolism (PE) was made based on computed tomographic angiography (CTA) with right ventricular strain and elevated cardiac biomarkers. A concomitant proximal DVT from the left common femoral to the distal peroneal vein was also noted. The patient's weight was 243kg with a calculated BMI of 72.3 kg/m2. After the patient had received parenteral anticoagulation with heparin for 4 days, it was decided to switch to Rivaroxaban 15mg BID for 21 days followed by 20 mg daily. With a history of irregular menses, the patient developed heavy menstrual bleeding (HMB) following the initiation of rivaroxaban. Her hemoglobin remained stable with no blood transfusion requirements. However, this led to the decision to switch to rivaroxaban 20 mg PO daily earlier than planned due to a lack of improvement in menstrual bleeding which was considered to be clinically relevant non-major bleeding (CRNMB). Despite this switch, there was no effect on efficacy and the patient did not develop any signs or symptoms of VTE recurrence during her prolonged hospital stay with a significant improvement in her oxygenation levels and VTE symptomatology. In our patient, we demonstrated the use of rivaroxaban in a morbidly obese individual with a BMI>70 by achieving therapeutic anti-Xa levels. Figure 1 shows the therapeutic peak and trough anti-Xa levels throughout the patient's hospitalization. The highest Anti Xa level of 314 mcg/mL was reported on day 19 correlating with the patient's menorrhagia, which self-limited with the transition from rivaroxaban 15 mg twice daily to 20 mg daily. Discussion: Two pivotal clinical trials, the EINSTEIN-DVT/PE trials, where 14% of patients in both arms weighed >100 kg, showed that patients on rivaroxaban (15 mg BID for 3 weeks, followed by 20 mg once daily) vs those on enoxaparin followed by a vitamin K antagonist, had no significant difference in recurrence rates of VTE and bleeding rates [Moore KT, et Al. Influences of Obesity, Am J Med 2017]. A recent post-hoc analysis of the EINSTEIN DVT/PE trials also portrayed no correlation between weight/BMI and risk of recurrent VTE or bleeding in those who received rivaroxaban. Our case illustrates the attainment of therapeutic anti-Xa levels with no recurrent VTE in our morbidly obese patient. Despite her heavy menstrual bleeding, the bleeding was controlled once the switch to rivaroxaban 20mg daily was completed. Another study in which its heaviest participant at 172 kg, showed compelling evidence that morbid obesity has minimal influence on the safety and efficacy of rivaroxaban [Speed V, et al. Fixed dose rivaroxaban. JTH 2020]. This remains true for our patient at 243 kg. Conclusion: Our case demonstrates that standard doses of rivaroxaban for the treatment of DVT/PE in individuals with morbid obesity with BMI>70 kg/m2 can be effective, and safer for the initial phase of treatment for VTE and in prevention of VTE recurrence. It also portrays that increased dosages attempting to account for high bodyweight/fat can potentially result in major bleeding events. Despite the 2021 ISTH guidelines, further prospective studies and randomized controlled trials are warranted, to assess the safety and efficacy of DOACs in VTE, particularly in such challenging clinical scenarios like morbid obesity. Alongside clinical assessment, additional studies will be essential to evaluate the need for universal and external validation of anti-Xa levels in patients taking DOACs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Anticoagulation Treatment and Outcomes of Venous Thromboembolism by Weight and Body Mass Index: Insights From the Veterans Health Administration.

Consensus statements have recommended against the use of direct oral anticoagulants (DOACs) in venous thromboembolism (VTE) for patients ≥120 kg and ≥40 kg/m2. We sought to determine use and outcomes of DOACs for VTE across weight and body mass index (BMI). We performed a retrospective cohort study of patients with first-time VTE 2013 to 2018 that were treated with DOAC or warfarin in the Veterans Health Administration. The Veterans Health Administration has implemented system-wide guidance for patient selection and shared decision-making for use of DOACs in VTE at extremes of weight. We stratified patients by weight and BMI and assessed (1) association of weight and BMI category to outcomes in those prescribed DOAC; and (2) association of DOAC, as compared to warfarin, to outcomes by weight and BMI categories. Outcomes of interest included major bleeding, clinically relevant nonmajor bleeding, and recurrent VTE. The analysis cohort included 51 871 patients prescribed DOAC or warfarin within 30 days of index VTE diagnosis (age 64.5±13.1 years; 6.0% female; median weight 93.4 kg [25th-75th: 80.5-108.6 kg]). For patients ≥120 kg (N=6934 patients), 38.4% were treated with DOAC, as compared to 45.4% of those ≥60 to <100 kg (N=30 645; P<0.0001). DOAC prescription was not associated with major bleeds, clinically relevant nonmajor bleeds, or recurrent VTE for those in higher weight and BMI categories as compared to those in average weight and BMI categories. DOAC prescription, as compared to warfarin, was not associated with increased recurrent VTE in any weight or BMI category. Patients ≥120 kg and ≥40 kg/m2 with VTE are frequently prescribed DOAC by the Veterans Health Administration, without an increase in bleeding or recurrent VTE. These findings suggest DOACs can be safe and effective in this population and may argue for broader adoption of pharmacy policies that promote careful patient selection and shared decision making.

Anticoagulant treatment satisfaction with warfarin and direct oral anticoagulants for venous thromboembolism

Treatment options for patients with venous thromboembolism (VTE) include warfarin and direct oral anticoagulants (DOACs). Although DOACs are easier to administer than warfarin and do not require routine laboratory monitoring, few studies have directly assessed whether patients are more satisfied with DOACs. We surveyed adults from two large integrated health systems taking DOACs or warfarin for incident VTE occurring between January 1, 2015 and June 30, 2018. Treatment satisfaction was assessed using the validated Anti-Clot Treatment Scale (ACTS), divided into the ACTS Burdens and ACTS Benefits scores; higher scores indicate greater satisfaction. Mean treatment satisfaction was compared using multivariable linear regression, adjusting for patient demographic and clinical characteristics. The effect size of the difference in means was calculated using a Cohen’s d (0.20 is considered a small effect and ≥ 0.80 is considered large). We surveyed 2217 patients, 969 taking DOACs and 1248 taking warfarin at the time of survey. Thirty-one point five percent of the cohort was aged ≥ 75 years and 43.1% were women. DOAC users were on average more satisfied with anticoagulant treatment, with higher adjusted mean ACTS Burdens (50.18 v. 48.01, p < 0.0001) and ACTS Benefits scores (10.21 v. 9.84, p = 0.046) for DOACs vs. warfarin, respectively. The magnitude of the difference was small (Cohen’s d of 0.29 for ACTS Burdens and 0.12 for ACTS Benefits). Patients taking DOACs for venous thromboembolism were on average more satisfied with anticoagulant treatment than were warfarin users, although the magnitude of the difference was small.

Abstract 15444: Anticoagulation Treatment of Venous Thromboembolism Across the Weight Spectrum: Insights From the Veterans Health Administration

Introduction: In seminal trials of venous thromboembolism (VTE) treatment with direct oral anticoagulants (DOAC), few patients were enrolled at low and high body weights to estimate treatment effects in these subgroups. Consensus statements have recommended against use of DOACs in VTE for patients ≥120 kg. We sought to describe real-world use of DOACs and other anticoagulants for VTE across the weight spectrum. Methods: We performed a retrospective cohort study of patients with first-time VTE that were treated with anticoagulants in the VA health care system from 2008 to 2018. We excluded patients with 1) additional indications for anticoagulation (atrial fibrillation and mechanical valves) and 2) no documented weight in the 90 days prior to 90 days after index VTE. We stratified patients by weight (&lt;60, 60 to 119, ≥120 kg) and determined 1) index anticoagulation prescription in the 30 days after index VTE (DOAC, warfarin, and low molecular weight heparin or fondaparinux [LMWH/F] only) and 2) variables associated with DOAC prescription, as compared to warfarin, in those ≥120 kg. Results: After excluding 3,676 patients with missing weight, there were 111,774 patients with VTE (64±13 years, 6% female). The most common therapy was warfarin (66%), followed by DOAC (21%), and LMWH/F only (13%). Median weight was 92 kg (interquartile range: 28), with 13,753 patients (12%) with weight ≥120 kg. Across weight categories, proportion of patients receiving DOAC was similar. In patients ≥120 kg, after multivariate adjustment, multiple comorbidities were associated with warfarin prescription while chronic kidney disease was associated with DOAC prescription ( Table ). Conclusion: Weight ≥120 kg is common for VTE patients, with DOAC frequently prescribed despite consensus statements recommending DOAC avoidance. For patients ≥120 kg, comorbidities influence VTE treatment selection, and determination of optimal treatment strategies across the spectrum of comorbidities is needed.

Clinical Outcomes of Multiple Myeloma Patients Treated with Direct Oral Anticoagulants for Immunomodulatory Drug Associated Venous Thromboembolism

Introduction: Venous thromboembolism (VTE) is a common complication in multiple myeloma (MM) patients for several reasons; hematologic malignancy itself is a VTE risk factor and standard of care immunomodulatory drugs (IMiDs) in combination with dexamethasone (Dex) increase the risk further. This combination therapy has a mean VTE incidence of 21.5% in studies that did not use thromboprophylaxis and is recommended for all patients on IMiDs, although the optimal thromboprophylactic regimen remains uncertain. In clinical practice, aspirin (ASA) is commonly prescribed for VTE prophylaxis due to the ease of use. Despite this, the incidence of VTE remains between 7-14%. There is a growing body of literature supporting the efficacy and safety of direct oral anticoagulants (DOACs) for the treatment of VTE in cancer populations. We wanted to assess the incidence of VTE despite ASA prophylaxis at our institution and to further characterize the role of DOACs in the MM population. To do this, we performed a chart review of all MM patients who had been treated with lenalidomide and a DOAC, assessing for VTE development and patient outcomes. Methods: We conducted a retrospective chart review of patients with the diagnosis of MM treated with lenalidomide therapy at Fox Chase Cancer Center at Temple University Hospital or Cottman Avenue after Jan 1st, 2015 to July 2019. Eligible patients were identified through electronic medical record data mining for patients that had been diagnosed with MM, had been prescribed lenalidomide, had been taking ASA while on lenalidomide, and switched to rivaroxaban, edoxaban or apixaban. For comparison, the number of patients treated with lenalidomide and ASA who did not switch to a DOAC were also identified. Patient charts were reviewed for VTE development and bleeding complications after DOAC administration. Results: 132 patients were identified who had a diagnosis of MM and had been prescribed lenalidomide between Jan 1, 2015 and July 31, 2019. These patients were also prescribed aspirin except for three who were already on a DOAC prior to starting lenalidomide. Of the total 132 patients, only 17 were prescribed a DOAC. Six of the patients were on DOACs for reasons other than VTE (atrial fibrillation N=4, atrial flutter N=1, marantic endocarditis N=1). Eleven patients were started on DOACs for VTE; incidence of 8.3% in our myeloma population. However three of these VTEs occurred within one month of high dose melphalan chemotherapy and autologous stem cell rescue. These three patients had been off lenalidomide for over one month prior to VTE. Eight of the 17 patients with VTE developed clots in the setting of active MM and concurrent therapy with IMiD/Dex, independent of hospitalizations or other provoking factors. This is an incidence of 6.0% for VTE directly attributed to therapy. Six patients were on lenalidomide and Dex, while two patients developed VTE while on pomalidomide and Dex. No patients on lenalidomide experienced recurrent VTEs after being switched to therapeutic dose DOAC. One patient on pomalidomide/Dex did experience recurrent VTE. We examined all 17 patients who were on DOACs, 16 of which had been on IMiD and DOACs concurrently. Three had minor bleeding events which all resolved spontaneously. One patient had a major bleeding event, which was a fatal ruptured cerebral aneurysm while on a DOAC and ASA concurrently. Conclusion: The incidence of VTE in our patient population receiving IMiD/Dex while on ASA prophylaxis therapy was similar to what has been previously reported in the literature. We examined the clinical outcomes of 16 patients treated with IMiDs and DOACs concurrently and found few bleeding events. The one major bleed was likely precipitated by malignant hypertension and not a direct result of being on a DOAC. Taken together these results further support the growing body of evidence that DOACs are effective and safe treatments for VTE in cancer patients, including MM. Moving forward, our clinical experience with treatment dose DOACs supports the use of prophylactic dose DOACs to potentially further reduce the incidence of VTE in this high-risk population. Disclosures No relevant conflicts of interest to declare.

Prevention and Treatment of Cancer-Associated Venous Thromboembolism: a Review.

Patients with cancer have an increased risk of venous thromboembolism (VTE). Cancer-associated VTE is associated with an increased risk of morbidity and mortality. Treatment of VTE in cancer is associated with higher rates of recurrent thrombosis as well as major bleeding compared with the general population. The goal of this review is to provide a summary of current evidence for the prevention and treatment of cancer-associated VTE. Validated risk prediction models are available to aide clinicians in identifying patients with cancer with the highest risk of VTE. Those patients with intermediate to high risk of VTE may benefit from primary prophylaxis with apixaban or rivaroxaban. Low-molecular-weight heparin is superior to vitamin K antagonists for the treatment of cancer-associated VTE. There is mounting evidence to support use of the direct oral anticoagulants for VTE in patients with cancer. Decisions on type and duration of anticoagulation in patients with cancer, either for primary or secondary prevention, should be made on a case-by-case basis with taking into account the individual patient bleeding and thrombotic risk.

455Prediction of major bleeding in patients receiving DOACs for venous thromboembolism: a prospective cohort study

Abstract Background The accuracy of currently available bleeding scores in patients on treatment with direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) is undefined. Purpose In a prospective cohort of patients with VTE treated with DOACs, we evaluated the accuracy of the ATRIA, HAS-BLED, Kuijer, ORBIT, RIETE and VTE-BLEED risk scores in predicting major bleeding (according to ISTH definition). Methods The accuracy of different scores to correctly classify subjects into a defined risk category was assessed by the c-statistic. Results Overall, 1141 patients were evaluated and 1034 included in the study. The index event was pulmonary embolism in 509 patients (49.2%) and proximal deep vein thrombosis in the remaining patients (50.8%). During the 12-month study period, 26 major bleedings occurred in 25 patients (2.8% patient-year): 14 major bleedings occurred in the first 6 months of treatment and 12 from 6 to 12 months in the 654 patients remained on treatment. In the 12-month study period, the VTE-BLEED score showed the best predictive value for bleeding complications (c-statistics 0.674, 95% CI 0.593–0.755). The lowest incidence of major bleeding (0.3%) was observed in the low risk category of VTE-BLEED which includes 38% of patients. The highest incidence of major bleeding (7.1%) was observed in the high-risk category of ORBIT which includes 10.9% of patients. Conclusions The VTE-BLEED score had the best accuracy in predicting major bleeding during treatment with DOACs for VTE. Whether the VTE-BLEED score can be used for decision making on anticoagulation should be tested in a management study.

Comparative Efficacy and Safety of Direct Oral Anticoagulants and Warfarin for the Treatment of Deep Venous Thrombosis and the Prevention of Post-Thrombotic Syndrome

In recent years, clinical trials have shown that direct oral anticoagulants (DOACs) are at least as effective and safe as oral warfarin for the treatment of venous thromboembolism (VTE). However, there are few studies comparing efficacy and safety of different DOACs for VTE. The purpose of this study was to compare antithrombotic and hemorrhagic effects of different DOACs and warfarin in patients with acute deep venous thrombosis (DVT). In addition, we studied preventive effects of these anticoagulants on the post-thrombotic syndrome (PTS). Consecutive patients with acute DVT who were treated with anticoagulants were enrolled. The cumulative incidence of VTE recurrence and bleeding events was assessed. Furthermore, we assessed cumulative complete thrombus resolution and development of PTS. During the 3-year period, 264 patients were treated with anticoagulation alone. Of these, 69 patients (26%) received apixaban, 64 (24%) received edoxaban, 67 (25%) received rivaroxaban, and 64 (25%) received warfarin. There were no significant differences in mean age (P = .131), sex distribution (P = .858), body mass index (P = .392), distribution of DVT (proximal vs distal, P = .072), proportion of concomitant pulmonary embolism (P = .317), and duration of anticoagulation (P = .117) between the groups. The higher incidence of the recurrent VTE was found in the warfarin group; however, this was not statistically significant (log-rank, P = .478). Similarly, bleeding events were more common in the warfarin and rivaroxaban groups, and fewer bleeding complications were noted in the apixaban group; this did not result in any significant difference (log-rank, P = .303). In contrast, apixaban showed earlier thrombus resolution, and the cumulative thrombus resolution was highest in the apixaban group, followed by the rivaroxaban group (log-rank, P = .022,). Development of PTS was higher in the rivaroxaban and warfarin groups, but no significant difference was found in cumulative development of PTS (log-rank, P = .943). Although DOACs did not appear to differ in the recurrent VTE events, the bleeding complications, and the development of PTS, apixaban showed the earliest thrombus resolution among the anticoagulants studied. These results suggest that apixaban seems to be safer and more effective than some of its competitors in the management of acute DVT.

The role of direct oral anticoagulants in cancer-related venous thromboembolism: a perspective beyond the guidelines.

Cancer-related venous thromboembolism (Wickham et al., Intern Med J 42(6):698-708, 2012) is an important source of morbidity and mortality in that population. The standard of care for the treatment of cancer-related venous thromboembolism (VTE) is a low molecular weight heparin (LMWH) for long periods of time. The favorable clinical trial results for efficacy and safety and availability of direct oral anticoagulants (DOAC) have remodeled the care and options for treatment of venous thromboembolism in the adult population. The data of cancer population-subgroup analysis of those studies have shown that DOAC are as effective and safe as conventional long-term oral anticoagulation with vitamin K antagonists (VKA). Additionally, non-controlled retrospective and prospective cohort data have been published describing efficacy and safety outcomes for the use of DOAC in cancer-related VTE. Altogether, the results from clinical studies have shown that direct oral anticoagulants may represent a treatment option for cancer-related VTE and an alternative to anticoagulation with VKA. Little is known about the patient-centered and system-based variables that determine the use of DOAC outside consensus guidelines, neither is known the impact of different anticoagulant modalities in adherence and quality of life in cancer patients. The objectives of this manuscript are to summarize the clinical trial-based and cohort data of cancer patients treated with DOAC for VTE and to highlight the aspects that may influence adherent to therapy, effectiveness, and safety outcomes in the treatment of cancer-related VTE.

New anticoagulants in the management of venous thromboembolism in women

Objective diagnosis and treatment are important in optimizing clinical outcomes in patients with venous thromboembolism (VTE), and anticoagulants are the mainstay of treatment. Traditionally, anticoagulant therapy involves parenteral anticoagulants, overlapping with and followed by oral vitamin K antagonists. Recently, direct oral anticoagulants (DOACs), including the Factor Xa inhibitors rivaroxaban, apixaban and edoxaban, and the direct thrombin inhibitor dabigatran etexilate, have been developed to address limitations associated with traditional anticoagulant therapy. DOACs have recently been approved for the treatment of acute deep vein thrombosis (DVT) and pulmonary embolism (PE). Successful phase III trials have demonstrated their efficacy for the treatment of DVT and PE, with a potentially improved safety profile. Recent evidence suggests that women bleed more compared to men when treated with DOACs for VTE without differences in treatment efficacy. Future clinical trials should include outcomes stratified by sex, and should investigate the clinical impact of this sex-related safety difference.