Safety of Direct Oral Anticoagulants in Central Nervous System Malignancies

Patients with brain tumors are at high risk for thromboembolic complications and frequently require anticoagulation. Direct oral anticoagulants (DOACs) are a less burdensome treatment for cancer‐associated thrombosis with safety and efficacy comparable to those of low molecular weight heparin (LMWH); however, there are few data to support the use of DOACs in patients with brain tumors. The purpose of this study was to better understand the safety profile of anticoagulants in patients with primary and metastatic brain tumors, with particular interest in the safety and efficacy of DOACs. Our hypothesis was that DOACs are as safe and effective as LWMH in this population. This study was conducted through a single‐center retrospective chart review of 125 patients with primary and metastatic brain tumors on anticoagulation. Our primary outcomes were major bleeding and intracranial hemorrhage (ICH), with secondary outcomes of minor bleeding and recurrent thrombosis. The rate of major bleeding was 26% in the LMWH group versus 9.6% in the DOAC group (p = .03). The rate of ICH was 15% in the LMWH group versus 5.8% in the DOAC group (p = .09). The severity of ICH in both groups was low with median Common Terminology Criteria for Adverse Events version 5 scores of 2 in the LMWH group and 3 in the DOAC group. The rates of minor bleeding and recurrent thrombosis were low in both groups. Our conclusion is that DOAC use in patients with brain tumors is not associated with increased rates of major bleeding compared with LMWH and is a safe and effective option.Implications for PracticePatients with brain tumors are at high risk for venous thromboembolism and frequently require anticoagulation. Direct oral anticoagulants (DOACs) are less burdensome than low molecular weight heparin (LMWH) for treatment of thromboembolism, but there is concern in the community over increased risk of bleeding. This study provides much‐needed objective evidence that there are fewer major bleeding events in patients with brain tumors on DOACs compared to LMWH with similar efficacy. As the paradigm of anticoagulation in patients with cancer shifts from LWMH toward DOACs, this work is particularly meaningful as it suggests DOACs are safe and effective for patients with brain tumors.     

Treatment of Cancer‐Associated Venous Thromboembolism with Low‐Molecular‐Weight Heparin or Direct Oral Anticoagulants: Patient Selection,Controversies, and Caveats

The treatment of venous thromboembolism (VTE) in patients with cancer is challenging because these patients have increased risks of both recurrent VTE and major bleeding, along with patient‐specific and cancer‐related factors that influence the approach to treatment. Historically, anticoagulant therapy with low‐molecular‐weight heparin (LMWH), given for both initial and long‐term treatment, has been the preferred approach recommended by practice guidelines. Most recently, the National Comprehensive Cancer Network (NCCN) guidelines indicate that the direct oral anticoagulants (DOACs) apixaban, edoxaban, or rivaroxaban are preferred for patients without gastric or gastroesophageal lesions. DOACs have been associated with an increased risk of major bleeding in patients with gastrointestinal and possibly genitourinary cancers, and DOACs should either not be used (especially in those with intact intraluminal tumors) or be used with caution in patients with these cancers. Fatal or life‐threatening bleeding occurs with similar frequency with DOACs or LMWH, and most major bleeding with DOACs can be managed with transfusion and standard measures. The patient''s willingness and ability to comply with LMWH injections, and their treatment preference, should also be considered. Patients with cancer who have VTE should be treated with anticoagulation for a minimum of 6 months. Anticoagulation should be continued indefinitely while cancer is active or under treatment or if there are persistent risk factors for recurrent VTE. This article summarizes the evidence from clinical trials of LMWH and DOACs that underpins the NCCN guideline recommendations, addresses several controversies and caveats regarding anticoagulant treatment, and offers evidence‐based, practical suggestions on patient selection for treatment with DOACs.Implications for PracticeSeveral randomized trials support the addition of direct oral anticoagulants (DOACs) to the therapeutic armamentarium for cancer‐associated venous thromboembolism (VTE). These agents come with unique risks and patient‐ and cancer‐specific variables that must be evaluated during the course of a patient''s cancer care. This narrative review discusses findings from clinical trials of low‐molecular‐weight heparin and DOACs for the treatment of cancer‐associated VTE, evidence that supports the recent National Comprehensive Cancer Network guideline recommendations. A personalized approach to treatment is proposed that addresses patient selection for treatment with DOACs, factors that influence efficacy and safety, controversies and caveats, and suggestions for their resolution in clinical practice.     

Practice patterns and outcomes of direct oral anticoagulant use in myeloproliferative neoplasm patients

Myeloproliferative neoplasms (MPNs) are characterized by an increased risk of thrombosis and bleeding. Vitamin K antagonists (VKAs) are the historic anticoagulant recommended for use in MPNs. Direct oral anticoagulants (DOACs) are being increasingly used in general and cancer populations. However, DOAC safety and efficacy in MPN patients remains unclear. We characterized real-world practice patterns of DOAC use in MPN patients and evaluated thrombosis and bleeding risk. We conducted a retrospective cohort study of 133 MPN patients prescribed DOACs for venous thromboembolism (VTE), atrial fibrillation, or arterial thromboembolism (ATE). Practice patterns including duration of anticoagulation, dosing, and concomitant use of antiplatelet/cytoreductive agents, were heterogeneous among MPN patients. The 1-year cumulative incidence of thrombosis and bleeding on DOAC was 5.5% (1.5–9.5%) and 12.3% (6.4–18.2%) respectively. In comparison, reported bleeding rates in MPN patients on DOAC and VKAs are 1–3%. On multivariable analysis, prior history of thrombosis, use of dabigatran or edoxaban, and younger age were significantly associated with a higher risk of recurrent thrombosis, while leukocytosis was associated with a higher risk of bleeding on DOAC. The higher-than-expected bleeding rate found in our study indicates the continued need for rigorous evaluation of DOACs in this population.Subject terms: Myeloproliferative disease, Medical research     

Cabozantinib Safety With Different Anticoagulants in Patients With Renal Cell Carcinoma

BackgroundIn patients with renal cell carcinoma (RCC) on cabozantinib, venous thromboembolism (VTE) management remains challenging due to limited safety data regarding direct oral anticoagulants (DOACs) use in conjunction with cabozantinib. We investigated the safety of cabozantinib with different anticoagulants in patients with RCC.MethodsIn this retrospective multicenter study (9 sites), patients with advanced RCC were allocated into 4 groups: (1) cabozantinib without anticoagulation, cabozantinib with concomitant use of (2) DOACs, (3) low molecular weight heparin (LMWH), or (4) warfarin. The primary safety endpoint was the proportion of major bleeding events (defined per International Society on Thrombosis and Hemostasis criteria). The primary efficacy endpoint was the proportion of new/recurrent VTE while anticoagulated.ResultsBetween 2016 and 2020, 298 patients with RCC received cabozantinib (no anticoagulant = 178, LMWH = 41, DOAC = 64, and warfarin = 15). Most patients had clear cell histology (78.5%) and IMDC intermediate/poor disease (78.2%). Cabozantinib was first, second, or ≥ third line in 21.8%, 31.9%, 43.3% of patients, respectively. Overall, there was no difference in major bleeding events between the no anticoagulant, LMWH, and DOAC groups (P = .088). Rate of new/recurrent VTE was similar among anticoagulant groups. Patients with a VTE had a statistically significantly worse survival than without a VTE (HR 1.48 [CI 95% 1.05-2.08, P = .02]).ConclusionThis real-world cohort provides first data on bleeding and thrombosis complications in patients with RCC treated with cabozantinib with or without concurrent anticoagulation. DOACs appear safe for VTE treatment for patients with RCC on cabozantinib, but optimized anticoagulation management, including individualized risk-benefit discussion, remains important in clinical practice.     

Efficacy of edoxaban for the treatment of gynecological cancer-associated venous thromboembolism: analysis of Japanese real-world data

ObjectiveDirect oral anticoagulants (DOACs) are increasingly being used for the treatment of cancer-associated venous thromboembolism (CAT). However, there is limited evidence of the efficacy of DOACs for the treatment of gynecological CAT. Thus, this study aimed to investigate the efficacy and safety of edoxaban for the treatment of gynecological CAT using Japanese real-world data.MethodsWe reviewed the medical records of patients with 371 gynecological cancer who received edoxaban or vitamin K antagonist (VKA) between January 2011 and December 2018.ResultsAltogether, 211 and 160 patients were treated with edoxaban and VKA, respectively. Fourteen patients (6.8%) in the edoxaban group and 22 (13.8%) in the VKA group showed recurrence of venous thromboembolism (VTE). Cumulative VTE recurrence was not significantly different between the 2 groups (p=0.340). Adverse events occurred in 15 (7.1%) and 11 (6.9%) patients in the edoxaban and VKA groups, respectively (p=0.697). Subgroup analysis of the edoxaban and VKA groups according to different tumor types, including ovarian, endometrial, and cervical cancer, showed equivalent outcomes in terms of VTE recurrence and adverse events. Patients without pulmonary embolism (PE) were mostly omitted from initial unfractionated heparin (UFH) therapy prior to administration of edoxaban. However, this did not increase the recurrence of VTE.ConclusionThis study confirmed that edoxaban is effective and safe for the treatment of gynecological CAT. This finding was consistent for different types of gynecological cancer. Additionally, initial UFH therapy prior to the administration of edoxaban may be unnecessary for patients without PE.     

Preventing thromboembolic complications in cancer patients after surgery: a role for prolonged thromboprophylaxis

Patients undergoing major abdominal surgery for malignancy are at particularly high risk of developing VTE. Extra protection against this can be given to patients with cancer by using a higher dose of LMWH than normally used for prophylaxis, with no increase in bleeding complications. Despite thromboprophylaxis with high-dose LMWH for the first postoperative week, the rate of late VTE is estimated to be between 10% and 20%. A meta-analysis of two studies using dalteparin or enoxaparin has shown that prolonging thromboprophylaxis for a further 3 weeks significantly reduces the risk of late occurring VTE by 62%. Thromboprophylaxis with LMWH for at least one month should be considered in patients undergoing surgery for malignant disease.     

Cancer-associated thrombosis: focus on extended therapy with dalteparin

The increased risk of thrombosis-related morbidity and mortality in patients with cancer remains, even in the face of anticoagulant therapy. Moreover, recurrent venous thromboembolism (VTE) complicates the management of cancer and adversely affects quality of life and survival. Until recently, initial therapy with unfractionated heparin or low-molecular-weight heparin (LMWH) followed by long-term therapy with an oral anticoagulant was the standard of care for the secondary prevention of acute thromboembolism in most patients. However, according to the results of the CLOT trial (Randomized Comparison of Low-Molecular-Weight Heparin Versus Oral Anticoagulant Therapy for the Prevention of Recurrent VTE in Patients With Cancer), extended LMWH therapy with dalteparin represents an alternative to standard oral anticoagulation. In terms of efficacy, the incidence of recurrent VTE in patients receiving dalteparin was half that of those receiving warfarin (27 of 336 patients vs 53 of 336 patients, respectively), for a 52% relative risk reduction. The incidence of major bleeding in this trial was not significantly different in the two arms. Although this LMWH regimen is supported by the latest practice guidelines of the American College of Chest Physicians, the question of whether long-term treatment with LMWH in cancer patients actually affects survival apart from the benefits of thromboprophylaxis remains to be answered.     

Outpatient use of low molecular weight heparin monotherapy for first-line treatment of venous thromboembolism in advanced cancer

Background.

Evidence-based treatment guidelines recommend low molecular weight heparin (LMWH) monotherapy for cancer-associated venous thromboembolism (VTE). This analysis assessed the first-line treatment strategies for VTE in patients with advanced solid tumors.

Methods.

Using administrative data from advanced lung, prostate, colon, or breast cancer patients diagnosed between January 2000 and December 2007 at four HMOs with integrated delivery systems, patients with an inpatient or outpatient VTE diagnosed within 2 years after cancer diagnosis and an outpatient purchase of warfarin, LMWH, and/or fondaparinux anticoagulant within 7 days of the VTE diagnosis were identified. First-line outpatient VTE pharmacological treatment and factors independently associated with receipt/non-receipt of LMWH monotherapy were assessed.

Results.

Overall, 25% of the 1,089 eligible patients received LMWH monotherapy as primary VTE treatment. The percentage increased steadily over time from 18% among patients diagnosed in 2000 to 31% among those diagnosed in 2007. Factors associated with LMWH monotherapy included VTE diagnosis year, chemotherapy within 60 days prior to VTE diagnosis, history of VTE prior to cancer diagnosis, and invasive surgery in the 90 days following VTE diagnosis. Colorectal and prostate cancer patients versus lung cancer patients and stage III versus stage IV patients were less likely to be treated with LMWH monotherapy.

Conclusions.

Adoption of LMWH monotherapy as initial treatment for cancer-associated VTE was low but increased steadily over the study period. Future studies should explore reasons underlying the underutilization of this preferred evidence-based treatment as well as the comparative effectiveness of LMWH versus warfarin-based anticoagulation in real-world cancer patients with VTE.     

Cancer et récidive thromboembolique veineuse : non-respect des recommandations de traitement

Low-molecular-weight heparins (LMWH) are the reference curative treatment of venous thromboembolism (VTE) in patients with cancer. All international guidelines recommend the long-term use of LMWH given their demonstrated superiority compared to vitamin-K antagonists (VKA) in reducing VTE recurrence in this patient population without increased risk of bleeding. However, several studies consistently show a lack of adherence to treatment recommendations, which are applied at the very best in 50% of cases. This results in a loss of chance for patients with fragile prognosis and in whom VTE represents the second cause of death. Given the expected benefit and the increased VTE prevalence in patients with cancer, full awareness is necessary to implement programs aiming at improving the therapeutic management of cancer-associated VTE. This requires multidisciplinary consideration by qualified physicians involved in the management of patients with cancer-associated VTE such as oncologists, internists and those specialized in vascular disease and hemostasis.     

Long-term therapy of venous thromboembolism in cancer patients

Venous thromboembolism (VTE) is a common complication in cancer patients that results in significant morbidity and mortality. Long-term treatment options for cancer patients who experience VTE include vitamin K antagonists (VKAs), low molecular weight heparins (LMWHs), and inferior vena caval (IVC) filters. Cancer patients have a two- to fourfold higher risk for experiencing recurrent VTE and major bleeding during chronic VKA therapy than patients without malignancies. Recent randomized clinical trials have shown that LMWHs rather than oral VKAs are preferred for initial chronic treatment of VTE in patients with advanced cancer. One factor potentially limiting the broader use of LMWH for chronic therapy in the United States is its higher acquisition cost. Efficacy, cost, drug availability, patient comorbidities, and concomitant medications all need to be considered when selecting chronic VTE therapy. Cancer patients with VTE should be treated for as long as their disease is active to minimize the incidence of recurrence. Use of IVC filters should generally be reserved for patients at high risk for recurrent VTE who have contraindications to anticoagulation. Several new anticoagulants are being investigated that promise greater therapeutic choices and potentially better outcomes for cancer patients with VTE.     

Primary prevention and treatment of venous thromboembolic events in patients with gastrointestinal cancers - Review

Venous thromboembolism event (VTE) is a common and morbid complication in cancer patients. Patients with gastrointestinal cancers often suffer from symptomatic or incidental splanchnic vein thrombosis, impaired liver function and/or thrombocytopenia. These characteristics require a thorough risk/benefit evaluation for individual patients. Considering the risk factors for the development of VTE and bleeding events in addition to recent study results may be helpful for correct initiation of primary pharmacological prevention and treatment of cancer-associated thrombosis (CAT), preferably with low molecular weight heparins (LMWH). Whereas thromboprophylaxis is most often recommended in hospitalized surgical and non-surgical patients with malignancy, there is less agreement as to its duration. With regard to ambulatory cancer patients, the lack of robust data results in low grade recommendations against routine use of anticoagulant drugs. Anticoagulation with LMWH for the first months is the evidence-based treatment for acute CAT, but duration of secondary prevention and the drug of choice are unclear. Based on published guidelines and literature, this review will focus on prevention and treatment strategies of VTE in patients with gastrointestinal cancers.     

Managing thromboembolic disease in the cancer patient: efficacy and safety of antithrombotic treatment options in patients with cancer

Management of thromboembolic disease in patients with cancer can be challenging. Patients with cancer who have established thrombosis are at increased risk of recurrent VTE and of anticoagulant-associated bleeding compared to patients with no cancer. The optimal treatment of VTE in patients with cancer should lower the risk of recurrent VTE without increasing the risk of bleeding and ideally improve a patient's quality of life. Initial treatment of VTE in patients with cancer should be with LMWH, which may be administered, subcutaneously, at home. The current standard of care for long-term treatment of VTE remains oral anticoagulant, which should be administered for as long as the cancer is active. However, the use of oral anticoagulants can be problematic in these patients due to possible anorexia and vomiting. The efficacy and safety of long-term treatment of VTE in cancer patients with LMWH is currently under investigation.     

Does prolonged thromboprophylaxis improve outcome in patients undergoing surgery?

Patients undergoing major abdominal surgery, particularly for malignancy, are at increased risk of venous thromboembolism. Haemostatic markers of coagulation are raised for several weeks after surgery. A higher dose of low-molecular-weight heparin than normally used for thromboprophylaxis is effective in preventing post-surgical VTE in patients with cancer with no compromise on bleeding. Four weeks' of thromboprophylaxis with the LMWH dalteparin is significantly more effective than standard (1 week) thromboprophylaxis in preventing proximal DVT. A meta-analysis of studies comparing 4 weeks' with 1 week of thromboprophylaxis showed that prolonged thromboprophylaxis with LMWH following major abdominal surgery for malignancy significantly reduces the risk of late occurring DVT.     

Deep vein thrombosis in cancer: the scale of the problem and approaches to management.

Patients with cancer have long been recognised to be at high risk of venous thromboembolism (VTE), although the condition remains under diagnosed and under treated in these patients. As a consequence, the morbidity and mortality due to deep venous thrombosis and pulmonary embolism remains unacceptably high in this group. Furthermore, the management of VTE in the presence of malignancy is complex, due both to the effects of the cancer itself and its treatments. Conventional long-term management of VTE involves the use of vitamin K antagonists (VKAs), such as warfarin, to reduce the risk of recurrence. However, this approach is associated with a range of practical difficulties including the need for regular laboratory monitoring, the potential for drug interactions, in addition to the risk of treatment resistance and bleeding in patients with cancer. Recent research indicates that the use of low molecular weight heparin (LMWH) therapy instead of VKAs may be beneficial in these patients. In particular, evidence from a large clinical trial of the LMWH dalteparin indicates that this agent offers an effective alternative to VKAs in the long-term management of VTE, that is free from the practical problems associated with the use of VKAs and without increasing the risk of bleeding.     

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.     

Thromboembolische Komplikationen – Prophylaxe und Therapie im Fokus

Cancer patients are at increased risk of thromboembolic complications, which are commonly referred to as Trousseau’s syndrome. Besides the potentially dramatic effects of the tumor on the coagulation and fibrinolytic systems, various supportive measures and more specific cancer treatments, such as surgery or chemotherapy contribute to the pathophysiology of cancer-associated venous thromboembolism (VTE). Clinical trials have shown that long-term therapy with low-molecular-weight heparin (LMWH) is superior to secondary prophylaxis with vitamin K antagonists in the treatment of patients with cancer-associated VTE. Based on currently available clinical evidence it is not clear which cancer patient should be offered primary thromboprophylaxis with LMWH. In this respect, the individual risk profile which is substantially influenced by the general condition of the patient and possible co-morbidities have to be taken into account. Recent experimental and clinical studies have suggested that LMWH affects tumor biology at various levels and may thus be potentially beneficial as an adjunct in cancer therapy.     

Warfarin versus low-molecular-weight heparin therapy in cancer patients

The association between cancer and venous thromboembolism (VTE) is well established. Importantly, VTE is a significant cause of mortality in cancer patients. Although long-term warfarin (Coumadin(trade mark); Bristol-Myers Squibb; New York, NY) therapy is the mainstay of treatment for cancer patients with VTE, there are many practical problems with its use in this population. In particular, achieving therapeutic drug levels is difficult in cancer patients due to the increased risk of drug interactions, malnutrition, vomiting, and liver dysfunction in these patients. Moreover, cancer patients are at an increased risk of adverse effects of warfarin therapy. In contrast, low-molecular-weight heparins (LMWHs) are associated with a lower risk of adverse events compared with warfarin in patients with cancer. These agents also offer practical advantages compared with warfarin, including more predictable anticoagulant effects and ease of administration in addition to possible antineoplastic effects. Several LMWHs have demonstrated superior efficacy to warfarin in the secondary prevention of VTE. In particular, the LMWH, dalteparin (Fragmin; Pfizer; New York, NY), has recently been shown to have superior efficacy to warfarin in a large trial of patients with cancer and VTE without increasing the risk of bleeding. A randomized trial of dalteparin has also shown improved response rates and survival in patients with small cell lung cancer. In view of the availability of more effective and reliable alternatives to warfarin therapy in cancer patients, it is appropriate to reassess the role of warfarin therapy in patients with cancer and VTE. Further evaluation of the LMWHs for effects on cancer outcome is indicated.     

Direct oral anticoagulants in patients with hematologic malignancies

The anticoagulant treatment for patients with hematologic malignancies is low molecular weight heparin (LMWH), which is considered the safest in this particular patients setting. Although direct oral anticoagulants (DOACs) have proven their efficacy and safety in patients with cancer, their use can be challenging in patients with hematologic malignancies due to the peculiarity of these neoplasms: high thrombotic risk, possible onset of thrombocytopenia and concomitant anticancer therapies. The aim of our study was to evaluate the efficacy and safety of DOACs for venous thromboembolism or atrial fibrillation in patients with hematologic malignancies and plasmatic DOACs level during anticancer therapy and at time of bleeding or thrombotic complications. We evaluated patients with hematologic malignancies treated with DOACs for venous thromboembolism or atrial fibrillation—therapy was maintained until the platelet count was ≥50 × 10⁹/L. In case of concomitant anticancer treatment and haemorrhagic or thrombotic events, we checked DOACs plasma levels (trough and peak). The patients evaluated were 135: 104/135 were on anticancer therapy. We did not observe either thrombotic or major haemorrhagic adverse events. Minor bleedings occurred in 10 patients and clinical relevant non-major (CRNM) in two patients. There was a statistically significant correlation between bleedings and myelodysplastic syndrome. DOACs resulted effective and safe in patients with hematologic malignancies. DOACs plasma level can be helpful in suggesting an early dose adjustment to prevent haemorrhagic adverse event in patients on concomitant anticancer therapy. Larger prospective studies including hematologic patients are warranted to confirm the safety and efficacy of DOACs.     

FRAGMATIC: A randomised phase III clinical trial investigating the effect of fragm in?a dded to standard t herapy i n patients with lung c ancer

Background  

Venous thromboembolism (VTE) occurs when blood clots in the leg, pelvic or other deep vein (deep vein thrombosis) with or without transport of the thrombus into the pulmonary arterial circulation (pulmonary embolus). VTE is common in patients with cancer and is increased by surgery, chemotherapy, radiotherapy and disease progression. Low molecular weight heparin (LMWH) is routinely used to treat VTE and some evidence suggests that LMWH may also have an anticancer effect, by reduction in the incidence of metastases. The FRAGMATIC trial will assess the effect of adding dalteparin (FRAGMIN), a type of LMWH, to standard treatment for patients with lung cancer.     

The use of novel oral anticoagulants in cancer patients with venous thromboembolism

Venous thromboembolism (VTE) is not uncommon among patients with cancer and is one of the major causes of mortality and morbidity. Treatment with low-molecular-weight heparin (LMWH) is effective, yet accompanied by the need for daily administration of injections for a prolonged time and (even rarely) thrombocytopenia. The discovery of novel oral anticoagulants (NOACs) was based on an effort to improve the pharmacodynamic and pharmacokinetic properties of previous generation anticoagulants while maintaining efficacy without the need for daily subcutaneous administration and frequent laboratory monitoring. The MEDLINE database was searched using PubMed in order to find relevant studies on the use of NOACs in patients with active malignancy and VTE. Furthermore, critical reading of references in recently published studies and reviews was performed. NOACs appear to be at least equivalent to coumarin anticoagulants in terms of efficacy and safety and their administration is easier, but data specifically concerning patients with active malignancy or comparing them to LMWH in this specific clinical setting are not yet available. Furthermore, patients with active cancer present several unique characteristics and drawing conclusions from studies involving other patient groups may not be appropriate. Specific studies in cancer patients are still pending that will help decide if NOACs will be the drugs of choice in this group of patients in need of efficient and simple to administer treatments.