Incidental Venous Thromboembolism Research Articles

Incidence and risk factors for venous thromboembolism in the Cancer-VTE Registry pancreatic cancer subcohort

BackgroundThis substudy of the Cancer-VTE Registry estimated venous thromboembolism (VTE) incidence and risk factors in pancreatic cancer patients.MethodsThe Cancer-VTE Registry was an observational study that collected VTE data from patients with solid tumors across Japan. We measured baseline VTE prevalence, and at 1-year follow-up, the cumulative incidence of symptomatic and composite VTE (symptomatic VTE and incidental VTE requiring treatment), bleeding, cerebral infarction/transient ischemic attack (TIA)/systemic embolic event (SEE), and all-cause death.ResultsOf 1006 pancreatic cancer patients, 86 (8.5%) had VTE at baseline, and seven (0.7%) had symptomatic VTE. Significant risk factors of baseline VTE were Eastern Cooperative Oncology Group performance status (ECOG PS) of 1, body mass index (BMI) ≥ 25 kg/m2, history of VTE, D-dimer > 1.2 µg/mL, and hemoglobin < 10 g/dL. At 1-year follow-up, the cumulative incidence of events was higher for pancreatic cancer vs other cancers. Pancreatic cancer patients with VTE vs those without VTE had significantly higher incidences of bleeding, cerebral infarction/TIA/SEE, and all-cause death. No significant risk factors for composite VTE were identified.ConclusionsThe cumulative incidence of composite VTE during cancer treatment was higher in pancreatic cancer than in other cancer types. Some risk factors for VTE prevalence at cancer diagnosis were identified. Although VTE prevalence at cancer diagnosis did not predict the subsequent 1-year incidence of composite VTE, it was a significant predictor of other events such as all-cause death in pancreatic cancer patients.Trial registrationUMIN Clinical Trials Registry; UMIN000024942

Comparison of long-term complications in cancer patients with incidental and acute symptomatic venous thromboembolism.

Clinical practice guidelines recommend that patients with incidental venous thromboembolism (VTE) receive the same anticoagulant therapy as those with symptomatic VTE. We aimed to compare the rate of complications between cancer patients with incidental and symptomatic VTE through a long-term follow-up cohort. We performed a post hoc analysis of prospective studies of cancer patients with VTE between 2008 and 2019, with the primary outcome of rates of recurrent VTE and clinically relevant bleeding (CRB) in incidental and symptomatic VTE groups. In total, 796 patients were included, of which 42.8% had incidental VTE. No significant differences were noted in the rate of recurrent VTE (0.4 per 100 patients/month vs. 0.5 per 100 patients/month; p = 0.313) and in the rate of CRB (0.6 per 100 patients/month vs. 0.5 per 100 patients/month; p = 0.128) between patients with incidental VTE and symptomatic VTE, respectively. At six-month follow-ups, the cumulative incidence of CRB was significantly higher in patients with incidental VTE than that in those with symptomatic VTE (7.9% vs. 4.4%, respectively; OR: 1.8; 95% CI: 1.01-3.2). Cancer patients with incidental VTE had similar rates of CRB and VTE recurrence in long-term follow-up compared with patients with symptomatic VTE. At six-month follow-ups, patients with incidental VTE had a higher cumulative incidence of CRB than those with symptomatic VTE.

Venous thromboembolism in Japanese patients with breast cancer: subgroup analysis of the Cancer-VTE Registry

BackgroundThis subgroup analysis of the Cancer-VTE Registry, a nationwide, large-scale, multicenter observational study with a 1-year follow-up, assessed real-world data on venous thromboembolism (VTE) among Japanese patients with breast cancer.MethodsPatients with stage II–IV pretreatment breast cancer screened for VTE at enrollment were included. During the 1-year follow-up period, incidences of VTE, bleeding, and all-cause death, and background factors associated with VTE risk were examined.ResultsOf 9,630 patients in the Cancer-VTE Registry analysis set, 993 (10.3%) had breast cancer (973 [98.0%] did not have and 20 [2.0%] had VTE at baseline). The mean age was 58.4 years, 73.4% of patients had stage II cancer, and 94.8% had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0. Risk factors for VTE at baseline by univariable analysis were age ≥ 65 years, ECOG PS of 2, VTE history, and D-dimer > 1.2 μg/mL. During follow-up, the incidence of symptomatic VTE was 0.4%; incidental VTE requiring treatment, 0.1%; composite VTE (symptomatic VTE and incidental VTE requiring treatment), 0.5%; bleeding, 0.2%; cerebral infarction/transient ischemic attack/systemic embolic event, 0.2%; and all-cause death, 2.1%. One patient with symptomatic VTE developed pulmonary embolism (PE) and died. Incidences of VTE and all-cause death were higher in patients with VTE vs without VTE at baseline.ConclusionsIn Japanese patients with breast cancer, VTE screening before initiating cancer treatment revealed a 2.0% prevalence of VTE. During follow-up, one patient had a fatal outcome due to PE, but the incidences of VTE were low.Clinical trial registrationUMIN000024942; UMIN Clinical Trials Registry: https://www.umin.ac.jp/ctr/.

Incidence and risk factors for venous thromboembolism in the Cancer-VTE Registry stomach cancer subcohort

BackgroundThe Cancer-VTE Registry was a large-scale, multicenter, prospective registry designed to investigate real-world data on venous thromboembolism (VTE) incidence and risk factors in adult Japanese patients with solid tumors. This pre-specified subgroup analysis aimed to estimate the incidence of VTE, including VTE types other than symptomatic VTE, and identify risk factors of VTE in stomach cancer from the Cancer-VTE Registry.MethodsStage II–IV stomach cancer patients who planned to initiate cancer therapy and underwent VTE screening within 2 months before registration were enrolled.ResultsOf 1,896 patients enrolled, 131 (6.9%) had VTE at baseline, but 96.2% were asymptomatic. Female sex, age ≥ 65 years, VTE history, and D-dimer > 1.2 μg/mL were independent risk factors of VTE at baseline. Notably, patients with D-dimer > 1.2 µg/mL at the time of cancer diagnosis had an approximately 20-fold risk of VTE. During follow-up, event incidences were symptomatic VTE, 0.3%; incidental VTE requiring treatment, 1.1%; composite VTE, 1.4%; bleeding, 1.6%; cerebral infarction/transient ischemic attack/systemic embolic events, 0.7%; and all-cause death, 15.0%. The incidence of all-cause death was higher in patients with VTE vs without VTE at baseline (adjusted hazard ratio 1.67; 95% confidence interval 1.21–2.32; p = 0.002).ConclusionsVTE prevalence at the time of cancer diagnosis was not negligible and was extremely high when the patients had high D-dimer. VTE screening by D-dimer before starting cancer treatment is advisable, even for asymptomatic patients, regardless of whether the patient is undergoing surgery or chemotherapy.Trial registrationUMIN000024942.

Risk of recurrent cancer-associated thrombosis after discontinuation of anticoagulant therapy

BackgroundClinical guidelines suggest continuing anticoagulation therapy for >6 months for patients with active cancer and venous thromboembolism (VTE). However, data regarding the safety of its discontinuation are scarce. ObjectivesTo valuate the risk factors and the incidence of recurrent VTE 6 months after the discontinuation of anticoagulation therapy in patients with cancer-associated thrombosis (CAT). MethodsWe performed a retrospective study on consecutive patients with CAT recruited between 2008 and 2019. The primary and secondary outcomes were recurrent VTE at 6 and 12 months, respectively. Sensitivity analyses were conducted to investigate the possible heterogeneity of these effects. ResultsA total of 311 patients were included, among whom 33.4% had metastases and 30.8% were still receiving oncological treatment after 6 months of anticoagulant therapy. At 6 and 12 months, the incidences of recurrent VTE were 6.1% (95% CI, 3.5–9.4%) and 8.7% (95% CI, 5.8–12.4%), respectively. Recurrent VTE was more frequent in patients with metastases at 6 (sub-distribution hazard ratio [SHR] 3.83; 95% CI, 1.54–9.52) and 12 months (SHR 5; 95% CI, 2.2–11.5). Patients with incidental VTE had fewer recurrent events at 6 (SHR 0.3; 95% CI, 0.1–0.8) and 12 months (SHR 0.3; 95% CI, 0.1–0.6) after discontinuing the anticoagulant therapy. ConclusionThe incidence of recurrent VTE at 6 and 12 months following the discontinuation of anticoagulant therapy is higher in patients with CAT. Patients with metastases were at an increased risk of recurrent VTE, whereas patients with incidental VTE were at a lower risk.

Incidental Venous Thromboembolism in Cancer Patients

Incidental Venous Thromboembolism in Cancer Patients

EMERGING DATA FOR CANCER ASSOCIATED THROMBOSIS TREATMENT

Venous thromboembolism (VTE) is a common complication in patients with malignancies,resulting in deep vein thrombosis, pulmonary embolism and central venous catheter VTE, and is responsible for high morbidity and mortality (1). The prevalence of cancer-associated thrombosis is increasing because of multiple factors, including longer patient survival, anticancer therapies, increased detection of incidental VTE during surveillance imaging, and wider use of central venous catheters. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) was the standard of care for the treatment of cancer-associated thrombosis, with vitamin K antagonists providing a secondary treatment option, until direct oral anticoagulants (DOAC) emerged as alternative first-line treatment options in 2016 (2). Rivaroxaban, Edoxaban and Apixaban are recommended as initial treatment in patients with cancer-associated thrombosis who are not at high risk of gastrointestinal or genitourinary bleeding (3). LMWHs and Fondaparinux are still recommended for prophylaxis of VTE in medically-treated patients with cancer. Rivaroxaban and Apixaban can be used selectively for thromboprophylaxis in patients with malignancies at high risk of VTE, for example in patients with pancreatic cancer or myeloma (4,5). Anticoagulant choice should incorporate a personalised medicine approach that considers cancer type, VTE and bleeding risk factors, drug–drug interactions (DDI), and patient preferences. Patients with cancer often experience narrow therapeutic index polypharmacy and undergo treatment for several simultaneous comorbidities. In this setting the risk of DDI is high in particular during therapy with tyrosine kinase inhibitors (6). Concerns on DDI management include decreased efficacy and bleeding risk. In general, DOAC use is not advisable in combination with drugs that are strong inhibitors of both P-gp and/or CYP3A4 for high bleeding risk and in combination with strong inducers of Pgp and/or CYP3A4 that could markedly reduce DOAC plasma levels. Routine use of plasma level measurements for DOAC, only available in few laboratory centres, is not currently recommended (7). Nevertheless it has recently become increasingly clear that clinicians need to assess the anticoagulant status of a patient receiving anticancer therapies. The global coagulation Test of thrombin generation (TGT) a sensitive method to assess the anticoagulant therapy, provides a global measure of anticoagulant effect by measuring the inhibition of formation of thrombin (FIIa), a common endpoint for both LMWH and FXa inhibitors (8). Furthers studies are warranted to better define the future role of this coagulation test in this subgroup of patients.

Concomitant Deep Vein Thrombosis in Cancer Patients with Unsuspected Pulmonary Embolism.

Simple SummaryCancer patients have a significantly higher risk of developing venous thromboembolism during their disease course when compared with the general population. During routine staging or follow-up imaging studies, incidental venous thromboemboli, including incidental pulmonary embolisms, can be identified. Identifying factors associated with incidental or unsuspected venous thromboembolism is important and can improve the management plan. In the current study, we found that 20.9% of patients with unsuspected pulmonary embolisms had concomitant deep vein thrombosis, and most of these patients were asymptomatic. In addition, we found that concomitant deep vein thrombosis increases the odds of venous thrombosis recurrence in cancer patients presenting with unsuspected pulmonary emboli. Therefore, for patients with isolated incidental subsegmental pulmonary embolism and concomitant deep vein thrombosis, initiating anticoagulants if no contraindications exist is recommended. In addition, the presence of concomitant deep vein thrombosis among cancer patients with unsuspected pulmonary embolisms is associated with poor short- and long-term outcomes in these patients.Incidental venous thromboembolism (VTE) is common in cancer patients and identifying factors associated with these events can improve the management plan. We studied the characteristics of concomitant deep vein thrombosis (C-DVT) in cancer patients presenting with unsuspected pulmonary embolism (PE) and the association of C-DVT with VTE recurrence and survival outcomes. Patients presenting to our emergency department with confirmed unsuspected/incidental PE between 1 January 2006 and 1 January 2016, were identified. Radiologic reports were reviewed to confirm the presence or absence of C-DVT. Logistic regression analyses and cox regression modeling were used to determine the effect of C-DVT on VTE recurrence and survival outcomes. Of 904 eligible patients, 189 (20.9%) had C-DVT. Patients with C-DVT had twice the odds of developing VTE recurrence (odds ratio 2.07, 95% confidence interval 1.21–3.48, p = 0.007). The mortality rates among C-DVT were significantly higher than in patients without. C-DVT was associated with reduced overall survival in patients with unsuspected PE (hazard ratio 1.33, 95% confidence interval 1.09–1.63, p = 0.005). In conclusion, C-DVT in cancer patients who present with unsuspected PE is common and is associated with an increased risk of VTE recurrence and poor short- and long-term survival. Identifying other venous thrombi in cancer patients presenting with unsuspected PE is recommended and can guide the management plan. For patients with isolated incidental subsegmental pulmonary embolism and concomitant deep vein thrombosis, initiating anticoagulants if no contraindications exist is recommended.

One-Year Incidences of Venous Thromboembolism, Bleeding, and Death in Patients With Lung Cancer (Cancer-VTE Subanalysis)

IntroductionThis subanalysis aimed to provide real-world data on venous thromboembolism (VTE) from patients with lung cancer in the Cancer-VTE Registry. MethodsThe primary outcome was the number of baseline VTE events in patients with lung cancer. The 1-year cumulative incidences of symptomatic VTE; composite VTE (symptomatic and incidental VTE requiring treatment); bleeding; cerebral infarction, transient ischemic attack, and systemic embolic events; and all-cause death were calculated. Clinical trial registration: UMIN000024942. ResultsThe study enrolled a total of 2377 patients with lung cancer; of these, 119 (5.0%) had VTE (six [0.3%], symptomatic, and 113 [4.8%], asymptomatic) and 14 (0.6%) had pulmonary embolism at baseline. During the follow-up period (mean, 337.7 d), the incidence was 0.6% for symptomatic VTE, 1.8% for composite VTE, 1.5% for bleeding events, 1.3% for cerebral infarction, transient ischemic attack, and systemic embolism, and 19.1% for all-cause death. Composite VTE frequency did not vary by anticancer drug type. Patients with (versus without) VTE at baseline had higher hazard ratios (HRs) for composite VTE (unadjusted HR: 5.29; Gray test p < 0.001) and symptomatic VTE (unadjusted HR: 4.89; Gray test p = 0.007). Patients with VTE at baseline had higher HRs for bleeding events (unadjusted HR: 3.27; Gray test p = 0.010) and all-cause death (unadjusted HR: 2.73; log-rank test p < 0.001) than patients without. In multivariable analysis, patients with baseline VTE prevalence and Eastern Cooperative Oncology Group Performance Status of 2 had increased composite VTE risk during cancer therapy. There were no other risk factors for composite VTE. ConclusionsOur findings emphasize the importance of VTE screening at cancer diagnosis.

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.

Clinical characteristics and outcomes of incidental venous thromboembolism in cancer patients: Insights from the Caravaggio study

BackgroundClinical guidelines advise similar anticoagulant treatment for symptomatic and incidental cancer‐associated venous thromboembolism (VTE). We investigated clinical features and outcomes of cancer patients with incidental or symptomatic VTE randomized in the Caravaggio study. ObjectivesWe performed a predefined sub‐analysis of the Caravaggio study in order to investigate the clinical features and outcomes of incidental and symptomatic VTE in patients with cancer. The relative efficacy and safety of apixaban and dalteparin in patients with incidental and symptomatic VTE was also assessed. MethodsThe Caravaggio study compared apixaban to dalteparin for the 6‐month treatment of cancer‐associated VTE. The primary efficacy and safety outcomes were recurrent VTE and major bleeding. ResultsTwo hundred thirty patients (20%) had incidental and 925 (80%) symptomatic VTE. Pulmonary embolism with or without deep vein thrombosis as index event, colorectal cancer, Eastern Cooperative Oncology Group (ECOG) score of 0, and locally advanced or metastatic cancer were more frequent in patients with incidental VTE. Deep vein thrombosis as index event, hematological cancer, and ECOG score of 2 were more frequent in patients with symptomatic VTE. Ten patients (4.3%) with incidental and 68 (7.4%) with symptomatic VTE had recurrent VTE (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.29–1.10). Major bleeding occurred in 12 (5.2%) patients with incidental VTE and in 33 (3.6%) patients with symptomatic VTE (HR 1.43, 95% CI 0.74–2.77). When comparing apixaban to dalteparin in patients with symptomatic and incidental VTE, the HR for recurrence was 0.73 (95% CI 0.45–1.19) and 0.41 (95% CI 0.11–1.56), respectively, and the HR for major bleeding 0.93 (95% CI 0.47–1.83) and 0.96 (95% CI 0.31–2.96), respectively. ConclusionsCompared to cancer patients with symptomatic VTE, those with incidental VTE have different clinical features at presentation, with a numerically lower incidence of recurrent VTE and a numerically higher incidence of major bleeding.

Outcomes among patients with cancer and incidental or symptomatic venous thromboembolism: A systematic review and meta‐analysis

Patients with cancer have an increased risk of venous thromboembolism (VTE) and it is commonly detected incidentally. The outcomes and optimal management for patients with cancer and incidental VTE remain debated. We conducted a systematic review and meta-analysis to evaluate the outcomes in patients with cancer and incidentally detected VTE compared to those with symptomatic events. We searched the electronic databases and included randomized controlled trials (RCTs) and observational studies reporting recurrent VTE, major bleeding events, and mortality in patients with cancer and incidental VTE compared to symptomatic VTE. We included 23 studies for the systematic review: 3 RCTs and 20 observational studies. The meta-analysis of the 3 RCTs showed a significantly lower rate of VTE recurrence at 6months in patients with incidental VTE compared to those with symptomatic VTE (relative risk [RR] 0.62, 95% confidence interval [CI] 0.44-0.87). The risk of major bleeding events at 6months was numerically higher with incidental VTE compared to symptomatic VTE (RR 1.47, 95% CI 0.99-2.20). There was no difference in overall mortality. Among patients with cancer, incidental VTE was associated with a lower rate of VTE recurrence compared to symptomatic VTE, with a trend in increased major bleeding events. The risk-benefit ratio of anticoagulation may differ between incidental and symptomatic events and should be considered in patient management.

Clinical Risk Factors Associated with Recurrent Venous Thromboembolism and Major Bleeding in Gastrointestinal Cancer Patients Receiving Doacs for Secondary Thromboprophylaxis

IntroductionCancer associated venous thromboembolism (VTE) is associated with a significant morbidity and mortality burden in cancer care, and anticoagulation offers a survival benefit. Recurrent VTE and major bleeding complications due to secondary prophylaxis remain a salient issue in treating patients with cancer associated-VTE, regardless of validated risk assessment models. Gastrointestinal (GI) cancers confer an increased risk for recurrent VTE and bleeding. We evaluated our current institutional utilization of Direct Oral Anticoagulants (DOACs) in patients with active GI malignancies addressing both efficacy and safety profiles with these agents. We estimated the association strength between each risk factor and the outcomes to further contribute in future risk assessment tools.MethodsThis is a retrospective chart review of patients receiving DOACs with histologically proven GI malignancy and a symptomatic or incidental VTE treated at the University of Arizona Cancer Center from November 2013 to February 2017. Patients were excluded if DOACs were prescribed for any other reason not related to VTE: VTE was determined to be in the context of a non-GI malignancy or when anticoagulation was contraindicated. The primary efficacy outcome was defined as documented recurrent deep vein thrombosis (DVT), nonfatal pulmonary embolism (PE), or fatal PE before and after 6 months of DOAC therapy. The secondary safety outcome was defined as documented major bleeding (hemoglobin reduction of ≥2 g/dL, requirement of transfusion of ≥2 units of Packed Red Blood Cells, bleeding in a critical site, or bleeding contributing to death) before and after 6 months of therapy. Descriptive statistical analyses were utilized. The t- test was performed to compare continuous variables. Fisher exact test is used for testing the difference in categorical variables. Odds ratios were used to compare the relative odds of the occurrence of the outcome given exposure to the risk factor. The 95% confidence interval (CI) was used to estimate the precision of the OR. Results were determined to be ‘statistically significant’ when this value was less than or equal to 0.05.ResultsOur review included 62 patients with balanced baseline characteristics whom were prescribed apixaban (n=28) and rivaroxaban (n=34) [Table 1]. Primary outcome events at 6 months were 4.8% in total (2 DVT & 1 PE); 7.4% (2 DVT) for patients on apixaban and 2.9% (1 PE) for those taking rivaroxaban. Beyond 6 months on DOACs therapy, 6.4% of patients experienced recurrent VTE (1 DVT event in the apixiban subgroup). Secondary outcome events at 6 months were 11.2% total (7 major bleeds), 7.1% (n=2) and 14.7% (n=5) for apixaban and rivaroxaban respectively. There were 2 bleeds contributing to death (hemopericardium and upper GI bleed) and 2 other bleed in critical sites (subarachnoid hemorrhage and retroperitoneal) in the rivaroxaban group, with all other adverse outcomes being upper or lower GI bleeds. Including those events beyond 6 months, 17.7% of patients had recorded bleeding events (2 additional major bleeds for each therapy). Significant predictors of a primary or secondary outcome were pancreatic cancer (OR, 9.6, 95% CI, 1.48 to 62.16, p =0.017), stage IV disease (OR, 15, 95% CI, 7.55 to 297.63, p = 0.0075) and high Khorana Score [≥3] (OR, 7.5, 95% CI, 1.3 to 43.92, p= 0.0238). Those who suffered a primary or secondary outcome were 67 times more likely to die within a month period, compared to those who completed their therapy (CI, 5.33 to 854.82, p = 0.0011).ConclusionsCancer associated VTE remains a challenging clinical scenario with a lack of data for utilization of DOACs in the setting of secondary prophylaxis. The utilization of DOACs in cancer patients provides another therapy for VTE secondary prophylaxis treatment, which must be weighed, based on safety profiles in our study population. The utilization of rivaroxaban led to a higher bleeding rate in patients, with both apixaban and rivaroxaban showing similar efficacy for prophylaxis. This study warrants further exploration of DOACs in the setting of VTE treatment for patients on active chemotherapy who are at high risk of recurrent VTE. In addition, further evaluation of clinical predictors that may influence the risk of VTE recurrence and major bleeding is warranted. Wide confidence intervals reflect of our sample size and future studies may benefit from multi-center participation to maximize sample size. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Cancer and Thrombosis: New Treatments, New Challenges.

The direct-acting oral anticoagulant (DOAC) has become an alternative to low-molecular-weight heparin (LMWH) for treatment and prophylaxis of venous thromboembolism (VTE) in cancer patients. The clinicians are, however, faced with difficult decisions regarding DOAC treatment: Which patients cannot use DOACs? Should incidental VTE be treated similar to symptomatic VTE? Is it safe to give DOACs to patients with gastrointestinal or urogenital cancers? How about drug–drug interactions? Should all cancer patients receive thromboprophylaxis? Is arterial thrombosis a problem? The current article reviews the available literature regarding these questions and aims to provide practical solutions based on data from the clinical trials and new guidelines.

Association Between Anticoagulation Outcomes and Venous Thromboembolism History in Chronic Thromboembolic Pulmonary Hypertension.

Background: The association between anticoagulation outcomes and prior history of venous thromboembolism (VTE) in chronic thromboembolic pulmonary hypertension (CTEPH) has not been established. This study aimed to compare the efficacy and safety of anticoagulation treatment in CTEPH patients with and without prior history of VTE.Methods: A total of 333 CTEPH patients prescribed anticoagulants were retrospectively included from May 2013 to April 2019. The clinical characteristics were collected at their first admission. Incidental recurrent VTE and clinically relevant bleeding were recorded during follow-up. The Cox proportional regression models were used to identify potential factors associated with recurrent VTE and clinically relevant bleeding.Results: Seventy patients (21%) without a prior history of VTE did not experience recurrent VTE during anticoagulation. Compared to CTEPH patients without a prior history of VTE, those with a prior history of VTE had an increased risk of recurrent VTE [2.27/100 person-year vs. 0/100 person-year; hazard ratio (HR), 8.92; 95% confidence interval (CI), 1.18–1142.00; P = 0.029] but a similar risk of clinically relevant bleeding (3.90/100 person-year vs. 4.59/100 person-year; HR, 0.83; 95% CI, 0.38–1.78; P = 0.623). Multivariate Cox analyses suggested that a prior history of VTE and interruption of anticoagulation treatments were significantly associated with an increased risk of recurrent VTE, while anemia and glucocorticoid use were significantly associated with a higher risk of clinically relevant bleeding.Conclusions: This study is the first to reveal that a prior history of VTE significantly increases the risk of recurrent VTE in CTEPH patients during anticoagulation treatment. This finding should be further evaluated in prospective studies.

Vascular Imaging in the Asymptomatic High-risk Cancer Population: A Role for Thrombosis Screening and Therapy Management.

We retrospectively examined the venous thromboembolism (VTE) events diagnosed in the Prophylaxis of High-Risk Ambulatory Cancer Patients Study (PHACS), a multi-center randomized trial, to assess the value of screening vascular imaging for the diagnosis of incidental VTE in high-risk cancer patients. A total of 117 asymptomatic cancer patients with a Khorana score ≥3 starting a new systemic chemotherapy regimen were enrolled in a prospective randomized control trial. Patients underwent baseline venous ultrasound (US) of the lower extremities (LEs) and screening contrast-enhanced chest computed tomography (CT). Those without preexisting VTE were then randomized into observation or dalteparin prophylaxis groups and were screened with serial US every 4 weeks for up to 12 weeks and imaged with contrast-enhanced chest CT at 12 weeks. Any additional imaging performed during the study period was also evaluated for VTE. Baseline prevalence of incidental VTE was 9% (n=10) with 58% percent of VTEs diagnosed by screening US. Incidence of VTE in the randomized phase of the trial was 16% (n=16) with 21% (n=10) of patients in the control arm and 12% (n=6) of patients in the dalteparin arm developing VTE, a non-significant 9% absolute risk reduction (HR=0.69, 95% CI 0.23-1.89). Sixty-nine percent of these patients were asymptomatic with 31% of patients diagnosed by screening US. Adding screening US to routine oncologic surveillance CT in high-risk ambulatory cancer patients with a Khorana score ≥3 can lead to increased VTE detection, with potential for decreased morbidity, mortality, and health care spending.

Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy.

Venous thromboembolism (VTE) often complicates the clinical course of cancer. The risk is further increased by chemotherapy, but the trade-off between safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain. This is the third update of a review first published in February 2012. To assess the efficacy and safety of primary thromboprophylaxis for VTE in ambulatory cancer patients receiving chemotherapy compared with placebo or no thromboprophylaxis, or an active control intervention. For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 3 August 2020. We also searched the reference lists of identified studies and contacted content experts and trialists for relevant references. Randomised controlled trials comparing any oral or parenteral anticoagulant or mechanical intervention to no thromboprophylaxis or placebo, or comparing two different anticoagulants. We extracted data on risk of bias, participant characteristics, interventions, and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively. We applied GRADE to assess the certainty of evidence. We identified six additional randomised controlled trials (3326 participants) for this update, bringing the included study total to 32 (15,678 participants), all evaluating pharmacological interventions and performed mainly in people with locally advanced or metastatic cancer. The certainty of the evidence ranged from high to very low across the different outcomes and comparisons. The main limiting factors were imprecision and risk of bias. Thromboprophylaxis with direct oral anticoagulants (direct factor Xa inhibitors apixaban and rivaroxaban) may decrease the incidence of symptomatic VTE (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.18 to 1.06; 3 studies, 1526 participants; low-certainty evidence); and probably increases the risk of major bleeding compared with placebo (RR 1.74, 95% CI 0.82 to 3.68; 3 studies, 1494 participants; moderate-certainty evidence). When compared with no thromboprophylaxis, low-molecular-weight heparin (LMWH) reduced the incidence of symptomatic VTE (RR 0.62, 95% CI 0.46 to 0.83; 11 studies, 3931 participants; high-certainty evidence); and probably increased the risk of major bleeding events (RR 1.63, 95% CI 1.12 to 2.35; 15 studies, 7282 participants; moderate-certainty evidence). In participants with multiple myeloma, LMWH resulted in lower symptomatic VTE compared with the vitamin K antagonist warfarin (RR 0.33, 95% CI 0.14 to 0.83; 1 study, 439 participants; high-certainty evidence), while LMWH probably lowers symptomatic VTE more than aspirin (RR 0.51, 95% CI 0.22 to 1.17; 2 studies, 781 participants; moderate-certainty evidence). Major bleeding was observed in none of the participants with multiple myeloma treated with LMWH or warfarin and in less than 1% of those treated with aspirin. Only one study evaluated unfractionated heparin against no thromboprophylaxis, but did not report on VTE or major bleeding. When compared with placebo or no thromboprophylaxis, warfarin may importantly reduce symptomatic VTE (RR 0.15, 95% CI 0.02 to 1.20; 1 study, 311 participants; low-certainty evidence) and may result in a large increase in major bleeding (RR 3.82, 95% CI 0.97 to 15.04; 4 studies, 994 participants; low-certainty evidence). One study evaluated antithrombin versus no antithrombin in children. This study did not report on symptomatic VTE but did report any VTE (symptomatic and incidental VTE). The effect of antithrombin on any VTE and major bleeding is uncertain (any VTE: RR 0.84, 95% CI 0.41 to 1.73; major bleeding: RR 0.78, 95% CI 0.03 to 18.57; 1 study, 85 participants; very low-certainty evidence). In ambulatory cancer patients, primary thromboprophylaxis with direct factor Xa inhibitors may reduce the incidence of symptomatic VTE (low-certainty evidence) and probably increases the risk of major bleeding (moderate-certainty evidence) when compared with placebo. LMWH decreases the incidence of symptomatic VTE (high-certainty evidence), but increases the risk of major bleeding (moderate-certainty evidence) when compared with placebo or no thromboprophylaxis. Evidence for the use of thromboprophylaxis with anticoagulants other than direct factor Xa inhibitors and LMWH is limited. More studies are warranted to evaluate the efficacy and safety of primary prophylaxis in specific types of chemotherapeutic agents and types of cancer, such as gastrointestinal or genitourinary cancer.

Retrospective Real-World Analysis of the Primary Safety Outcomes in Venous Thromboembolism of High-Risk Major Bleeding Cancer Patients Receiving Therapeutic Anticoagulation

Introduction The therapeutic anticoagulation of cancer-associated venous thromboembolism (VTE) is challenging because of the increased risk for thromboembolic recurrence and major bleeds (MB). Direct oral anticoagulants (DOACs) have emerged over Low Molecular Weight Heparin (LMWH) as a preferred treatment option by improving efficacy without compromising safety. Despite these advantages, major bleeding was noted to be a safety concern in recent randomized clinical trials, mainly for gastrointestinal (GI) and genitourinary (GU) high-risk cancer patients. We evaluated our cancer center's institutional experience to determine the safety signals among VTE treatments and clinical risk factors which can predict an adverse outcome to further develop our clinical practice decisions in oncology patients. Methods This is a retrospective chart review of patients receiving DOACs and LMWH with histologically proven GI or GU malignancy and symptomatic or incidental VTE treated at The University of Arizona Cancer Center from November 2013 to February 2020. Patients were excluded if DOACs were prescribed for any other reason not related to VTE, or the thrombotic event was determined to be unrelated to active malignancy. The primary safety outcome was defined as documented major bleeding by hemoglobin reduction of ≥2 g/dL, transfusion of ≥2 units of Packed Red Blood Cells, bleeding in a critical site, or bleeding contributing to death. The secondary efficacy outcome was defined as documented recurrent deep vein thrombosis (DVT), nonfatal pulmonary embolism (PE), or fatal PE. Data was collected as individually and composite outcome (MB+rVTE) before six months. Continuous non-normally distributed data are compared using the non-parametric Kruskal-Wallis Rank Sum. Categorical data are compared using χ2 or Fisher's exact test. Logistic regression was used to assess the relationship between anticoagulant therapy and the 3 outcome measurements. The relationship between therapies was adjusted for clinical risk factors using logistic regression. Statistical analyses were performed using Stata16. Results Our review included 160 patients with similar baseline characteristics who were prescribed enoxaparin (n=53), apixaban (n=55), and rivaroxaban (n=52) except for white race and active smokers [Table 1]. Primary MB outcome events at six months were 7.5%, 10.9%, and 17.3% for enoxaparin, apixaban, and rivaroxaban, with no statistical difference among therapies or cancer type [p&amp;gt;0.05]. Secondary rVTE outcome events at six months were 7.5%, 3.6%, and 5.7% for enoxaparin, apixaban, and rivaroxaban, respectively, with no significant difference among therapies or cancer type [p&amp;gt;0.05]. There were no differences in individual or composite outcomes of LMWH, apixaban, rivaroxaban, or DOAC by GI or GU cancer type. There are no statistically significant clinical associations between anticoagulation therapy by the three outcome measurements in either GI or GU cancer. Beyond six months on enoxaparin, apixaban, and rivaroxaban, there were 5.6%, 3.6%, and 5.7% added events to MB, and 3.7%, 1.8%, and 0% to rVTE, respectively. Conclusions Our retrospective review has shown similar efficacy in preventing recurrent VTE among anticoagulants and indirectly equivalent to those published by the randomized clinical trials. Notably, the rate of MB for our real-world high-risk GI/GU cancer was 2.8 times higher in patients receiving DOACs compared to those on clinical trial [MB 6% SELECT-D Young et al. 2018 and MB 3.8% Caravaggio Agnelli et al. 2020] and in agreement with a recent meta-analysis [relative risk GI 1.9 and GU 4.9, Giustozzi et al. 2020]. We recognized there are inherited selection bias in both clinical trials and retrospective studies, although baseline characteristics are similar. Future clinical trial designs should consider including real-world high-risk patients according to associated clinical risk factors to aid in the appropriate choice of therapeutic anticoagulation. Disclosures No relevant conflicts of interest to declare.

Direct oral anticoagulants for cancer-associated venous thromboembolism: a systematic review and meta-analysis

AbstractDirect oral anticoagulants (DOACs) are an emerging treatment option for patients with cancer and acute venous thromboembolism (VTE), but studies have reported inconsistent results. This systematic review and meta-analysis compared the efficacy and safety of DOACs and low-molecular-weight heparins (LMWHs) in these patients. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and conference proceedings were searched to identify relevant randomized controlled trials. Additional data were obtained from the original authors to homogenize definitions for all study outcomes. The primary efficacy and safety outcomes were recurrent VTE and major bleeding, respectively. Other outcomes included the composite of recurrent VTE and major bleeding, clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality. Summary relative risks (RRs) were calculated in a random effects meta-analysis. In the primary analysis comprising 2607 patients, the risk of recurrent VTE was nonsignificantly lower with DOACs than with LMWHs (RR, 0.68; 95% CI, 0.39-1.17). Conversely, the risks of major bleeding (RR, 1.36; 95% CI, 0.55-3.35) and CRNMB (RR, 1.63; 95% CI, 0.73-3.64) were nonsignificantly higher. The risk of the composite of recurrent VTE or major bleeding was nonsignificantly lower with DOACs than with LMWHs (RR, 0.86; 95% CI, 0.60-1.23). Mortality was comparable in both groups (RR, 0.96; 95% CI, 0.68-1.36). Findings were consistent during the on-treatment period and in those with incidental VTE. In conclusion, DOACs are an effective treatment option for patients with cancer and acute VTE, although caution is needed in patients at high risk of bleeding.

Clinical characteristics, management, and outcome of incidental pulmonary embolism in cancer patients

AbstractIncidental pulmonary embolisms (IPEs) are common in cancer patients. Examining the characteristics and outcomes of IPEs in cancer patients can help to ensure proper management, promoting better outcomes. To determine the clinical characteristics, management, and outcomes of IPEs for cancer patients, we conducted a 1:2 ratio case-control study and identified all consecutive patients with IPE who visited the emergency department at The University of Texas MD Anderson Cancer Center between 1 January 2006 and 1 January 2016. Each IPE case was matched with 2 controls using a propensity score obtained using logistic regression for IPE status with other factors affecting overall survival. A total of 904 confirmed cases were included in the analysis. IPE frequently occurred during the first year after cancer diagnosis (odds ratio [OR], 2.79; 95% confidence interval [95% CI], 2.37-3.29; P < .001). Patients receiving cytotoxic chemotherapy had a nearly threefold greater risk of developing IPE (OR, 2.87; 95% CI, 2.42-3.40; P < .001). In-hospital mortality was 1.9%. The 7- and 30-day mortality rates among the cases were 1.8% and 9.9%, respectively, which was significantly higher than in the control groups: 0.2% and 3.1%, respectively (P < .001). IPE was associated with reduced overall survival (hazard ratio [HR], 1.93; 95% CI, 1.74-2.14; P < .001). Concurrent incidental venous thromboembolism was identified in 189 of the patients (20.9%) and was also associated with reduced overall survival (HR, 1.65; 95% CI, 1.21-2.25; P = .001). Our results show that IPE events are associated with poor outcomes in cancer patients. Proper management plans similar to those of symptomatic pulmonary embolisms are essential.