Background Previous studies suggest isolated distal deep vein thrombosis (IDDVT) has a self‐limited clinical course. However, these studies excluded cancer patients, who remain a high‐risk population. In addition, studies to evaluate the long‐term clinical outcomes of IDDVT in cancer patients have been limited. Here, we report outcomes from our experience in treating cancer‐associated IDDVT versus proximal venous thromboembolism (VTE). Methods We prospectively evaluated a cohort of patients referred to our cancer‐associated thrombosis clinic from August 2014 through May 2018. We compared clinical characteristics, anticoagulation prescription, VTE recurrence, overall survival, major bleeding, and subsequent hospital admission between cancer patients with IDDVT and proximal VTE. A propensity score matching method was used to reduce bias from confounding variables. Results Of 1100 patients referred to the clinic, 124 IDDVT and 178 proximal VTE events were analyzed. After propensity score matching, 96 patients were included in each cohort. There was no difference in the rate of recurrent VTE between cancer patients with proximal VTE vs IDDVT, with or without matching (matched: hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.31‐1.92; P = .58). There was no difference in overall survival between cancer patients with proximal VTE vs. IDDVT with or without matching (matched: HR, 1.18; 95% CI, 0.77‐1.82; P = .45). Furthermore, subsequent hospital admissions and major bleeding events were similar between patients with proximal VTE events versus IDDVT. Conclusions Cancer patients with IDDVT have similar outcomes as their proximal counterparts, including rate of recurrence and overall survival. These findings suggest treatment of cancer‐associated IDDVT should mirror treatment of proximal events.
Venous thromboembolism (VTE) is a common complication of cancer occurring in up to one-fifth of cancer patients. The risk of VTE, which includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is increased up to seven-fold in patients with cancer. While the indications and contraindications to treatment for VTE patients with cancer parallel to those patients without cancer, the treatment of VTE is challenging for cancer patients who are three-fold more likely to have VTE recurrence than patients without cancer and who are also at increased risk of bleeding. While anticoagulant therapy is recommended for most cancer patients with VTE, some patients may benefit from alternative interventions, such as thrombolysis, thromboembolectomy, or placement of an inferior vena cava (IVC) filter. Recent data support the use of direct oral anticoagulants (DOACs) for treatment of cancer-associated VTE in select cancer patients and for primary prevention of thromboembolism in high-risk cancer patients. Individualized decision-making, keeping in consideration the patient's risk for thrombotic and bleeding events is essential.
Introduction Randomized trials of venous thromboembolism (VTE) treatment in cancer have primarily focused on the initial 6-month period and the risk/benefit of additional anticoagulant therapy beyond this time point has not been fully evaluated. Current guidelines recommend continuing full dose anticoagulation after 6 months in patients who have ongoing active cancer and/or those undergoing anti-neoplastic treatment. This recommendation, however, is based on little evidence. Here, we describe clinical outcomes of patients who have completed at least 6 months of anticoagulation. Our aim was to compare VTE recurrence, bleeding rate, and overall survival in patients who continued vs. discontinued anticoagulation after the initial 6-month treatment period. Methods We evaluated a prospective cohort of patients referred to the Cleveland Clinic cancer-associated thrombosis clinic from 8/2014-12/2018. We evaluated clinical characteristics, VTE recurrence, bleeding (major or clinically relevant non-major bleeding (CRNMB) as defined by ISTH criteria), and overall survival in patients who continued vs. discontinued anticoagulation after 6 months. Low-risk for recurrent VTE was defined as not having active cancer and not receiving systemic therapy. Statistical methods included t-tests, chi-squared tests, Cox model, and log rank test where appropriate. Multivariable analysis was performed to analyze outcomes of interest. Results The study population was comprised 284 (73.2%) patients who were followed 6 months after the initial VTE event. Of these, 93 (32.7%) did not continue anticoagulation beyond 6 months, and 191 (67.3%) continued anticoagulation treatment (table 1). Anticoagulation was discontinued for the following reasons: low risk (n=33, 35.5%), bleeding (n=12, 12.9%), clinical decision (n=4, 4.3%) and other including financial reasons (n=43, 46.2%; table 2). In patients who continued anticoagulation, 86/191 (45%) had stage IV disease and the most frequent cancers were hematologic malignancies (58/191, 30.4%) and gastrointestinal cancers (37/191, 19.4%). Low molecular weight heparin was the most commonly prescribed anticoagulant (110/191; 57.6%) followed by direct oral anticoagulants (68/191, 35.6%). There was no difference in the rate of recurrent VTE in patients who remained on treatment beyond six months (23/191; 12%) vs. those who stopped treatment at six months (11/93; 11.8%; p= 0.81; figure 1). In patients who continued anticoagulation 6-12 months after the initial treatment period, 13/191 (6.8%) had a bleeding event (major bleeding n=4, CRNMB n=9). There was 1 major bleed and no CRNMB in the group that stopped anticoagulation. After multivariable analysis, recurrent VTE was associated with worse overall survival [hazard ratio (HR) 1.88; 95% Confidence Interval (CI) 1.06-3.35, p=0.03]. Discussion This prospective analysis found no difference in the rate of recurrent VTE and more bleeding in patients who continued anticoagulation, although recurrent VTE rates were high in both cohorts. Furthermore, a recurrent VTE event was associated with worse overall survival. Emerging data with DOACs may alter recurrence rates and the ability to continue treatment beyond 6 months. Although limited by a small study population, this study adds to available data regarding outcomes beyond six months of treatment. Future studies should focus on exploring the outcomes of extending anticoagulation and better identifying patients at risk for recurrent VTE. Disclosures McCrae: Rigel Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Pfizer Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Dova Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Sanofi Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Khorana:Janssen: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy.
Background: Emerging data suggest that treatment of cancer-associated venous thromboembolism (VTE) with direct oral anticoagulants (DOACs) results in lower recurrence rate compared to low molecular weight heparins (LMWHs) at 6 months but with concern for increase in bleeding risks. The objective of this study was to determine occurrence of major bleeding as well as recurrent VTE events on treatment with DOACs or LMWHs in a cohort study. Methods: The cancer-associated thrombosis (CAT) clinic is a centralized service for care of cancer patients with suspected deep venous thrombosis (DVT) and/or pulmonary embolism (PE) established at the Tausig Cancer Institute of the Cleveland Clinic. We conducted a prospective cohort study of patients referred to this clinic between 8/2014 through 1/2018. The demographics, cancer types, VTE characteristics, treatment courses, and outcomes (VTE recurrence, major or clinically relevant nonmajor [CRNM] bleeding) were recorded for these patients. Standards of treatment at the CAT clinic shifted in late 2017 from use of LMWH, enoxaparin, to a DOAC, rivaroxaban for cancer-associated VTE. Current exclusion criteria for rivaroxaban use include recent active bleeding, GFR < 30 mL/min, severe hepatic impairment, thrombocytopenia (platelet count < 50,000), and/or expected malabsorption at the level of stomach or small bowel. For cancer patients considered at higher risk of bleeding, including patients with luminal gastrointestinal cancers with an intact primary; cancers at risk of bleeding from genitourinary tract, bladder or nephrostomy tubes; or patients with active mucosal abnormalities such as duodenal ulcers, gastritis/esophagitis or colitis, treatment with LMWHs is preferred. Major or CRNM bleeding was determined according to definitions outlined by the International Society on Thrombosis and Haemostasis. Results: The study population included 258 patients with acute VTE. Of these, 239 patients had DVT (93%), 34 had PE (14%), 15 had both (6.2%), and 3 had visceral vein thromboses (1.2%). The patients were 53% male with a median age of 65 ± 16 years. The most common cancer types were hematologic malignancies (19.5%, n = 50), primary brain tumors (11.2%, n = 29), lung (8.5%, n = 22), breast (7.0%, n = 18), and pancreatic cancers (6.6%, n = 17). Enoxaparin monotherapy was prescribed for 72.1% (n = 179 of 248) of patients. Other treatments included rivaroxaban (17.3%, n = 43), apixaban (0.8%, n = 2), warfarin (2.8%, n = 7), dalteparin (0.4%, n = 1), or no anticoagulation (3.2%, n = 8). Major bleeding occurred in 5% (n = 12 of 241) of patients treated with anticoagulation at 6 months of the initial event, including 5.0% (n = 9 of 179) of patients on enoxaparin and 4.7% (n = 2 of 43) of patients on rivaroxaban, and these differences were not significant (p > 0.95) (Figure 1). CRNM bleeding was observed in 16.2% (n = 29 of 179) of patients on enoxaparin and 11.6% (n = 5 of 43) of patients on rivaroxaban. The common cancer types for patients with major bleeding events included primary brain tumors (n = 4), genitourinary cancers (n = 2) and gastrointestinal cancers (n = 2) (Table 1). The 1-year incident rate of recurrent VTE was 11% for patients treated with enoxaparin and 9% for those treated with DOACs, and 2-year rate was 13% and 11%, respectively (Figure 2). Overall, there was no significant difference in the VTE recurrence rate calculated by the competing risk model between patients on enoxaparin compared to rivaroxaban (p = 0.19). Conclusions: Bleeding events of patients treated with enoxaparin was comparable to rivaroxaban for both major and CRNM bleeding events in this carefully selected real-world population. Patients receiving rivaroxaban reported a statistically insignificant but lower rate of recurrent VTE compared to those receiving enoxaparin. These findings support a recent change in ISTH guidance recommending rivaroxaban or edoxaban as initial treatment of cancer-associated VTE in selected patients. Disclosures Khorana: Sanofi: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Pfizer: Consultancy.
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