Cancer-associated Venous Thromboembolism Research Articles

Dalteparin and Rivaroxaban Sequential Use in Cancer Patients with Venous Thromboembolism

To determine the effect and safety of sequential treatment with the low-molecular-weight heparin dalteparin and the direct oral anticoagulants rivaroxaban in patients with cancer- associated venous thromboembolism (VTE). Observational study. Department of Oncology, the Second Affiliated Hospital of Soochow University, between January 2017 and September 2019. Patients with active cancer, diagnosed with VTE and who received sequential treatment with dalteparin and rivaroxaban, were retrospectively reviewed. Logistic regression analysis was used to identify risk factors associated with VTE recurrence. Ninety-nine patients with active cancer were enrolled in the study. The median delteparin treatment time was nine days (5-20 days), and 2.8 months (1-6 months) for rivaroxaban. Sixty (60.6%) patients had eliminated VTE, and 39 (39.4%) had persistent VTE, but with relieved symptoms. No major bleeding was observed. Eleven (11.1%) patients had minor bleeding, including melena (5.1%), hematuria (3.0%), vaginal bleeding (1.0%), gingival bleeding (1.0%), and subcutaneous hemorrhage (1.0%). During the 6 months follow-up period, one (1.0%) developed pulmonary embolism, and seven (7.1%) experienced recurrent VTE. Univariate logistic regression analysis showed that bleeding occurrence and anticoagulant treatment duration were the two significant factors affecting VTE recurrence (p<0.05). Maintenance of rivaroxaban after initial dalteparin treatment could effectively reduce the risk of VTE recurrence and was well tolerated by patients with cancer-associated VTE. However, in the clinical practice, the treatment duration is often insufficient, so it is essential to follow-up these patients to ensure sufficient treatment time. Key Words: Venous thromboembolism, Low-molecular-weight heparins, Directly oral anticoagulants, Cancer.

Increasing Incidence and Declining Mortality After Cancer-Associated Venous Thromboembolism: A Nationwide Cohort Study

PurposeThe incidence of cancer-associated venous thromboembolism has increased, but whether short-term mortality after cancer-associated venous thromboembolism has changed remains uncertain. We investigated whether the increasing incidence of venous thromboembolism in cancer patients is associated with a change in mortality. MethodsWe used administrative medical registries to identify a cohort of all Danish patients diagnosed with a first primary cancer from 2006 to 2017. We examined temporal changes in 1-year risks of venous thromboembolism and in mortality risks at 30 days and 1 year after venous thromboembolism. Cox regression was used to assess changes in mortality rate ratios over time. ResultsWe included 350,272 cancer patients (median age 68 years, 49.1% female), of whom 8167 developed venous thromboembolism within 1 year after cancer diagnosis. The cumulative 1-year risk of venous thromboembolism was 1.8% in 2006-2008, increasing to 2.8% for patients diagnosed in 2015-2017. The 30-day mortality after venous thromboembolism decreased from 15.1% in 2006-2008 to 12.7% in 2015-2017, and the 1-year mortality decreased from 52.4% to 45.8%, equivalent to a hazard ratio (HR) of 0.83 (95% confidence interval [CI], 0.75-0.90). This pattern of declining 1-year mortality was consistent for patients with pulmonary embolism, HR 0.79 (95% CI, 0.69-0.90), and deep venous thrombosis, HR 0.76 (95% CI, 0.67-0.87). Lower mortality over time was evident across all strata of cancer stage, cancer type, and cancer treatment. ConclusionsThe 1-year risk of venous thromboembolism after a first primary cancer diagnosis in Denmark increased during 2006-2017. This increase was accompanied by declining mortality.

A retrospective real-world major bleeding (MB) comparison of direct oral anticoagulants (DOAC) and low molecular weight heparin (LMWH) in genitourinary cancer-associated venous thromboembolism (GU-CAVTE) with reported randomized clinical trials (RTC).

410 Background: MB is a serious complication in patients with CAVTE receiving treatment with DOAC or LMWH. The most recent meta-analysis of the four major RCT showed that MB events rate were similar among the DOAC and LMWH group, however, it was noted that MB occurred at GU site 4.9 times more in DOAC than LMWH patients. While GUCA (e.g. bladder and testicular) are considered to be high-risk based on the Khorana Score, they were underrepresented among the RCT ( &lt; 12%). We present a Real-World retrospective cohort study analyzing the MB rates in patients presenting with GU-CAVTE treated either by a DOAC or LMWH compared to those of the RTC. Methods: We performed a retrospective chart review of patients with a diagnosed GUCA and VTE who presented to The University of Arizona Cancer Center (UACC) and were subsequently placed on anticoagulant therapy with either a DOAC or LMWH from 11/2013-4/2020. MB outcome was defined as documented Hgb drop of ≥2 g/dL, ≥2 units of PRBC, MB in a critical site, or contributing to death. MB was extracted and compared from the SELECT D, ADAM VTE, and Caravaggio for DOAC and Hokusai for the LMWH control arm with the GUCA subgroup. Recurrent VTE was collected. In situations where there was insufficient data to categorize individuals, those individuals were excluded from the analysis. The proportion of MB reported in each study were compared using a binomial test. Results: Our review included 56 patients with similar baseline characteristics to the RCT, who were prescribed enoxaparin (n = 13), apixaban (n = 27) and rivaroxaban (n = 16). Our UACC data was compared to the RCT reported MB outcomes with rivaroxaban (12% vs 8%, [p = 0.63]), apixaban (11% vs 6%, [p = 0.40]), and LMWH (both 0 vs 1% [p = 0.67]). No statistical difference among DOAC selection [p = 0.90]. Our UACC rate of MB in patients with GUCA for both DOAC combined versus LWMH were 11.6% (5/43) and 0% [p = 0.1910], compared to the RCT GU subgroup was 5.7% (6/104) [p = 0.02] and 0.6% (1/175) [p = 1.0], respectively. Furthermore, our data found no statistical significance difference among the recurrent VTE rate among DOAC, LMWH, UACC Retrospective or RCT events. Conclusions: In agreement with the four major RCT, our study demonstrated that patients with high-risk GUCA and underlying VTE treated with a DOAC had a non-significant higher incidence of MB compared to those treated with LMWH. Further, our Real-World experience showed that GUCA DOAC had a significantly higher MB event rate compared to the RCT subgroup population. We acknowledge there are inherent biases in all retrospective studies and RCT. These data support the idea that DOAC should be further studied and used with caution in patients with a high risk of bleeding. We recommend LMWH being the safest anticoagulation modality for High-Risk Bleeding GU malignancy.

Comparison Between Non–vitamin K Antagonist Oral Anticoagulants and Low-Molecular-Weight Heparin in Asian Individuals With Cancer-Associated Venous Thromboembolism

It is unclear whether the clinical benefits associated with non-vitamin K antagonist oral anticoagulants (NOACs) are similar to those associated with low-molecular-weight heparins (LMWHs) in Asian individuals with cancer and acute venous thromboembolism (VTE). To compare the risk of recurrent thromboembolic events and bleeding associated with use of a NOAC vs use of the LMWH enoxaparin in Asian individuals with cancer-associated VTE. This cohort study was conducted using data from the Chang Gung Research Database, a multi-institutional electronic medical records database in Taiwan. A cohort of 1109 patients with cancer-associated VTE were identified between January 1, 2012, and January 31, 2019. Data were analyzed from March 2019 through December 2020. Receiving a NOAC (including rivaroxaban, apixaban, edoxaban, or dabigatran) or the LMWH enoxaparin. The primary outcomes were composite recurrent VTE or major bleeding. Stabilized inverse probability of treatment weighting was used to balance baseline covariates. We compared risks of recurrent VTE or major bleeding between groups using Cox proportional hazards models. In addition, we conducted an analysis using a Fine and Gray subdistribution hazard model that considered death as a competing risk. Among 1109 patients with cancer and newly diagnosed VTE, 578 (52.1%) were women and the mean (SD) age at index date was 66.0 (13.0) years; 529 patients (47.7%) received NOACs and 580 patients (52.3%) received the LMWH enoxaparin. Composite recurrent VTE or major bleeding occurred in 75 patients (14.1%) in the NOAC group and 101 patients (17.4%) in the enoxaparin group (weighted hazard ratio [HR], 0.77; 95% CI, 0.56-1.07; P = .11). The groups had similar risk of VTE recurrence (HR, 0.62; 95% CI, 0.39-1.01; P = .05) and major bleeding (HR, 0.80; 95% CI, 0.52-1.24; P = .32) at 12 months of follow-up. However, taking a NOAC was associated with a significantly lower risk of gastrointestinal bleeding compared with receiving enoxaparin (10 patients [1.9%] vs 41 patients [7.1%]; HR, 0.29; 95% CI, 0.15-0.59; P < .001). Findings for both primary outcomes were consistent with competing risk analyses (recurrent VTE: HR, 0.68; 95% CI, 0.45-1.01; P = .05; major bleeding: HR, 0.77; 95% CI, 0.51-1.16; P = .21). This cohort study found that in real-world practice, among Asian patients with cancer-associated VTE, use of a NOAC was associated with a similar risk for recurrent VTE or major bleeding compared with use of the LMWH enoxaparin. Nonetheless, use of a NOAC was associated with a significantly lower rate of gastrointestinal bleeding. Further prospective studies are needed to confirm these findings.

57-Year-Old Woman With Weakness and Word-Finding Difficulties

57-Year-Old Woman With Weakness and Word-Finding Difficulties

Cancer-Associated Venous Thromboembolism Treatment With Anti-Xa Versus Weight-Based Enoxaparin: A Retrospective Evaluation of Safety and Efficacy.

Venous thromboembolism (VTE) is a complication of cancer, for which low-molecular-weight heparin (LMWH) remains the preferred anticoagulant. Enoxaparin is traditionally dosed using weight. In certain populations, monitoring anti-Xa levels for therapeutic effect provides pharmacokinetic guidance for dose adjustments. There is a paucity of data regarding anti-Xa-directed enoxaparin dosing for treatment of VTE in patients with cancer. This study aims to evaluate efficacy (recurrent VTE) and safety (major bleed) between enoxaparin anti-Xa-guided dose adjustments and weight-based dosing in patients with cancer-associated VTE. This single-center, retrospective cohort study examined patients treated with enoxaparin for cancer-associated VTE using data from electronic health records. There were 674 patients who met the inclusion criteria, with 283 receiving anti-Xa-directed dose adjustments. Recurrent VTE, major bleed, or all-cause death occurred in 102 of 283 patients (36%) in the anti-Xa cohort and 166 of 391 patients (42.5%) in the weight-based cohort (hazard ratio [HR] = 0.73; 95% CI = 0.57-0.93; P = 0.01). When death was removed from the composite end point, there was no significant difference between the cohorts in recurrent VTE or major bleed (HR = 1.18; P = 0.38). In the anti-Xa cohort, a total of 1584 anti-Xa peak levels were collected, with 1324 (83.6%) drawn correctly in relation to enoxaparin administration. Of those, 714 (53.9%) were within therapeutic range. Patients with cancer receiving anti-Xa-guided enoxaparin dose adjustments for initial VTE, compared with weight-based dosing, had no significant difference in the rate of recurrent VTE or major bleed.

Clinical controversies in the treatment of cancer-associated venous thromboembolism.

Cancer-associated venous thromboembolism (VTE) is a common complication of malignancy. Patients with cancer exhibit risk factors for both recurrent VTE and major or minor bleeding. Direct oral anticoagulants (DOACs) are an attractive treatment option; however, there is a lack of consensus among national guidelines for choice between DOACs and LMWH, agent selection, dosing strategy, and duration of anticoagulation. Characteristics of the thrombotic event, the malignancy, the patient, and the anticoagulant must be considered. A systematic search of online databases was performed to identify literature on the management of cancer-associated VTE. Multiple controversies remain surrounding the optimal treatment of cancer-associated VTE.

Tissue factor-positive extracellular vesicles and cancer-associated venous thromboembolism

Tissue factor-positive extracellular vesicles and cancer-associated venous thromboembolism

Treatment Patterns and Clinical Outcomes in Korean Cancer Patients With Venous Thromboembolism: A Retrospective Cohort Study.

This study assessed epidemiologic data and clinical outcomes, including venous thromboembolism (VTE) recurrence and bleeding events, in patients with cancer-associated VTE, and assessed factors associated with clinical outcomes. Data were extracted from retrospective medical-chart review of adult patients diagnosed with cancer-associated deep vein thrombosis or pulmonary embolism who received anticoagulation treatment for ≥3 months. Patients were classified by: low-molecular-weight heparin (LMWH), direct oral anticoagulants (DOACs), and other anticoagulants. First VTE recurrence and bleeding events, and factors associated with their occurrence, were assessed during the initial 6 months of treatment. Overall, 623 patients (age: 63.7 ± 11.3 years, 49.3% male) were included (119, 132, and 372 patients in LMWH, DOACs and other anticoagulants groups, respectively). The cumulative 6-month incidence of VTE recurrence was 16.6% (total), 8.3% (LMWH), 16.7% (DOACs), and 20.7% (other); respective bleeding events were 22.5%, 11.0%, 12.3%, and 30.7%). VTE recurrence and bleeding rates differed only between LMWH and other anticoagulants (HR 2.4, 95% CI: 1.2-5.0 and 3.6, 1.9-6.8, respectively). These results highlight the importance of initial VTE treatment choice for preventing VTE recurrence and bleeding events. LMWH or DOACs for ≥3 months can be considered for effective VTE management in cancer patients.

A Case of Cancer Associated Venous Thromboembolism in Which DOAC Switching was Effective for Bleeding Complications

A Case of Cancer Associated Venous Thromboembolism in Which DOAC Switching was Effective for Bleeding Complications

Healthcare costs of patients with cancer stratified by Khorana score risk levels

Aims Patients with cancer are at high risk of venous thromboembolism (VTE), which entails a high economic burden. The risk of cancer-associated VTE can be assessed using the Khorana score (KS), a validated VTE risk prediction algorithm. This study compared healthcare costs associated with different KS in a population of patients newly diagnosed with cancer. Methods The Optum Clinformatics DataMart database (01/01/2012–09/30/2017) was used to select adult patients with ≥1 hospitalization or ≥2 outpatient claims with a cancer diagnosis (index date) initiated on systemic therapy or radiation therapy. Patients were classified in mutually exclusive cohorts based on KS (i.e. KS = 0, 1, 2 or ≥3). The observation period spanned from index to the earliest among the end of data availability, death, end of insurance coverage, or 12 months. Results In total 6,194 patients (KS = 0: 2,488; KS = 1: 2,125; KS = 2: 1,074; KS ≥ 3: 507) were included. On average, patients were aged 68 years, 48–52% were female, and the Quan–Charlson comorbidity index ranged between 1.1 and 1.4. Over the observation period, all-cause total healthcare costs per patient per month (PPPM) were $8,826 (KS = 0), $11,598 (KS = 1), $14,028 (KS = 2), and $16,211 (KS ≥ 3). Using the KS = 0 cohort as a reference, adjusted PPPM costs were $2,506, $4,775, and $6,452 higher in the KS = 1, KS = 2, and KS ≥ 3 cohorts, respectively. Hospitalization and outpatient costs were the main drivers of these differences. Similar results were found for VTE-related costs, which represented 4–11% of the total all-cause cost difference between KS cohorts. Limitations Residual confounders; results may not be generalized to patients with other insurance plans or those who received treatments other than systemic therapy or radiation therapy. Conclusions This real-world analysis found that cancer patients at higher risk of VTE (based on KS) incurred significantly greater all-cause and VTE-related healthcare costs compared with cancer patients at lower risk of VTE.

Direct Oral Anticoagulants for the Treatment of Venous Thromboembolism in Patients With Active Cancer.

Although direct oral anti - coagulants (DOACs) are as safe and effective as conventional anticoagulants for treating venous thromboembolism (VTE), we have insufficient evidence justifying their use in patients with active cancer. We investigated the safety and effectiveness of DOACs in patients with active cancer. To investigate the safety and efficacy of DOACs, we retrospectively extracted 312 consecutive patients with active cancer who were prescribed edoxaban, rivaroxaban or apixaban for VTE. The most common primary cancer sites were the lung, stomach, colon/rectum, hematology, ovary, and pancreas. Fifty patients (16%) discontinued DOACs due to clinically relevant bleeding; major bleeding events occurred in 18 patients (5.4%). Thrombosis reduced or resolved in 144 of 167 evaluable patients (86%). In particular, pulmonary embolism was reduced or resolved in 46 of 50 patients (92%). Our findings revealed that DOACs for cancer-associated VTE are as safe and effective as conventional anticoagulation therapy.

Solid Tumor Complicated With Venous Thromboembolism: A 10-Year Retrospective Cross-Sectional Study

Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT) occurs more frequently in cancer patients than in the general population. A retrospective cross-sectional study was carried out in patients with solid tumor complicated with VTE admitted to the Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 1st, 2008 and December 31th, 2017. The incidence of VTE in hospitalized cancer patients was 1.8%, twice the incidence of VTE in hospitalized non-cancer patients. The annual incidence of cancer-associated VTE in our center varied between 1.6% in 2015 and 0.4% in 2009 with an overall average incidence of 1.3% over the research decade. BMI values of 549(67.7%) cancer patients were within the normal range, but none of patients had BMI greater than 35 kg/m2. 747(92.1%) cancer patients had ECOG PS score ≤ 2 and 481(59.3%) had distant metastasis. Patients with pancreatic, bladder, ovarian and endometrial cancer had the highest incidence of VTE. Upper extremity DVT (47.2%) was more common in cancer patients and might be closely associated with CVC (74.9%), while lower extremities DVT (36.1%) intended to PE development (15.0%). The annual incidence rates showed a fluctuating and upward trend over the research decade. VTE occurrence was closely related to tumor stage, tumor site, catheterization and anti-neoplasm therapy in cancer patients.

Pharmacokinetics of edoxaban in EGFR-mutated non-small cell lung cancer patients with venous thromboembolism.

The risk of venous thromboembolism (VTE) is increased 7-fold in patients with cancer than in those without. Low-molecular-weight heparin is the standard treatment for cancer-associated VTE. Direct oral anticoagulants (DOACs) are not inferior to low-molecular-weight heparin with respect to the general outcome of recurrent VTE. Warfarin is associated with a risk of bleeding when used in combination with gefitinib or erlotinib which are epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). It is unclear, however, whether combination treatments with EGFR-TKIs and DOACs pose the same risk. We aimed to identify anticancer drugs and anticoagulants that can be used safely in combination, as accompanying research to an observational study on VTE incidence rates in lung cancer patients (Rising-VTE/NEJ037 study). Twelve patients receiving EFGR-TKI monotherapy and VTE treatment were enrolled. Blood samples were collected in time series after the first dose of edoxaban, and further samples were collected within 8-15 days after administering EGFR-TKIs. The pharmacokinetics (PK) of edoxaban were analyzed using a non-compartmental model. Edoxaban concentrations (30mg once daily) were measured in eight patients. PK analyses showed no significant differences before and after co-administration of EGFR-TKIs (gefitinib, erlotinib, and afatinib). Our findings indicate that the PK of edoxaban was not considerably affected by co-administration of EGFR-TKIs (gefitinib, erlotinib, and afatinib).

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 PRACTICE: Several 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.

Approach to Cancer-Associated Thrombosis: Challenging Situations and Knowledge Gaps.

Malignancy is a significant risk factor for venous thromboembolism (VTE). It is estimated that up to 20% of patients with cancer may develop VTE at some time in their cancer journey. Cancer-associated VTE can lead to hospitalizations, morbidity, delayed cancer treatment, and mortality. The optimal prevention and management of cancer-associated thrombosis (CAT) is of utmost importance. Direct oral anticoagulants have been recommended as first-line therapy for VTE treatment in the general population and their efficacy has recently been demonstrated in the cancer population, leading to increased use. However, patients with cancer have unique challenges and comorbidities that can lead to increased risks and concerns with anticoagulation. Herein we will discuss commonly encountered challenges in patients with CAT, review available literature, and provide practice suggestions. IMPLICATIONS FOR PRACTICE: This article aims to specifically address cancer-associated thrombosis issues for which there is limited or absent evidence to guide best practice, for circumstances that pose unique challenges for clinicians, and for directions when the literature is conflicting. It reviews pertinent data for each selected topic and provides guidance for patient management based on the best available evidence and experiences from the panel.

NATF Cancer-Associated Thrombosis Project: Introduction.

An outstanding group of medical oncologists, hematologists, cardiologists, and epidemiologists developed a series of manuscripts on management approaches for the prevention and treatment of cancer-associated venous thromboembolism. This article introduces this multidisciplinary collaborative effort.

Prediction and Prevention of Cancer-Associated Thromboembolism.

Venous and arterial thromboembolism are prevalent, highly burdensome, and associated with risk of worse outcomes for patients with cancer. Risk for venous thromboembolism (VTE) varies widely across specific cancer subpopulations. The ability to predict risk of cancer-associated VTE is critical because an optimal thromboprophylaxis strategy is best achieved by targeting high-risk patients with cancer and avoiding prophylaxis in patients with cancer at low risk for VTE. A validated risk tool for solid tumors has been available for a decade. Newer tools have focused on specific populations, such as patients with multiple myeloma. Emerging studies continue to optimize risk prediction approaches in patients with cancer. Recent randomized trials have specifically addressed risk-adapted thromboprophylaxis using direct oral anticoagulants, and revised guidelines have included these new data to formulate recommendations for outpatient thromboprophylaxis. Implementation science approaches to enhance use of outpatient prophylaxis in the context of these guideline changes are under way. However, major knowledge gaps remain, including a lack of data for inpatient thromboprophylaxis in the cancer setting and a lack of formal tools for identifying risk of bleeding. This review describes optimal approaches to risk prediction and patient selection for primary pharmacologic thromboprophylaxis of cancer-associated VTE, addresses barriers to implementing these practices, and highlights strategies to overcome them. IMPLICATIONS FOR PRACTICE: Risk for venous thromboembolism (VTE) varies widely among patients with cancer. Individual risk can be determined using validated approaches. Inpatient and postsurgical thromboprophylaxis is more widely accepted. However, most patients with cancer develop VTE in the outpatient setting. Recent randomized trials have demonstrated benefit to risk-adapted outpatient thromboprophylaxis. High-risk patients may therefore be considered for outpatient thromboprophylaxis as recommended by recently updated guidelines. System-wide implementation approaches are necessary to improve compliance with prophylaxis.

Clinicopathological Characteristics of Cancer-associated Venous Thromboembolism (CAT-VTE) from a Medicolegal Autopsy

Clinicopathological Characteristics of Cancer-associated Venous Thromboembolism (CAT-VTE) from a Medicolegal Autopsy

Bleeding with Apixaban and Dalteparin in Patients with Cancer-Associated Venous Thromboembolism: Results from the Caravaggio Study.

Direct oral anticoagulants are recommended for the treatment of cancer-associated thrombosis (CAT) as an alternative to low-molecular-weight heparin (LMWH), but an increased bleeding risk in patients with gastrointestinal cancer was reported. The Caravaggio study compared apixaban and dalteparin for the treatment of patients with CAT. Here we describe sites of bleeding, associated cancer sites, clinical presentation, and course of major bleeding in patients included in the Caravaggio study. The Caravaggio study was a multinational, randomized, open-label, noninferiority study. Bleeding events and the severity of major bleedings were adjudicated by a committee unaware of treatment allocation using predefined criteria; for the purpose of this analysis, data were analyzed in the safety population. Major bleeding occurred in 22 of 576 patients on apixaban (3.8%) and in 23 of 579 patients on dalteparin (4.0%). The sites of major bleeding and their distribution according to the type of cancer were similar between the two treatment groups. Major bleeding occurred in nine patients with gastrointestinal cancer in each treatment group. The clinical presentation of major bleeding was severe or fatal in 6 patients on apixaban and in 5 patients on dalteparin, while the clinical course was severe in 5 patients on apixaban and in 7 patients on dalteparin. Apixaban is a safe alternative to LMWH for the treatment in patients with CAT. No excess in gastrointestinal bleeding was observed in patients who received apixaban, including those with gastrointestinal cancer.