A Pilot Study in Cancer Patients with Central Venous Catheter Associated Deep Vein Thrombosis in Upper Extremity Treated with Rivaroxaban (Catheter 2)

Abstract Introduction Upper extremity deep vein thrombosis (UEDVT) represents up to 10% of cases of venous thromboembolism (VTE) and is frequently associated with central venous catheter (CVC) placement in patients receiving chemotherapy for cancer. UEDVT may be treated with low molecular weight heparin (LMWH) either as monotherapy or subsequently transitioned to warfarin as we have previously shown (Kovacs 2007). Whereas for non-cancer VTE rivaroxaban is at least as efficacious and safe as warfarin, the latter is problematic in cancer patients and direct oral anticoagulants (DOACs) such as rivaroxaban have not been studied to date in this setting. In this study weevaluated thesafety and efficacy of rivaroxaban in the treatment of UEDVT secondary to CVC in patients with cancer. Methods We conducted a multicentre prospective cohort study at 3 centres in Canada between December 2012 and January 2016. We enrolled patients ≥18 years of age with active malignancy and symptomatic proximal UEDVT (axillary or more proximal) with or without pulmonary embolism (PE), associated with a CVC. Exclusion criteria included dialysis catheters, active bleeding, platelet count <75 x 109/L, creatinine clearance <30 mL/min, other anticoagulants, PE with hemodynamic instability, inability to infuse through the catheter after a trial of intraluminal thrombolytic therapy (tissue plasminogen activator,tPa), patients with acute leukemia, patients with multiple myeloma awaiting bone marrow transplant within 3 months, thrombosis involving the brachial,basilic or cephalic veins only, treatment for >7 days with other anticoagulant, need for dual antiplatelet therapy (recent stent), or concomitant use of P-glycoprotein and CYP3A4 inhibitors. Primary objective was an estimate of the proportion of catheter survival at 3 months, defined as infusion failure that does not respond to 2 mg oftPa. Secondary objectives included recurrence of DVT, PE, major bleeding, clinically relevant non-major bleeding (CRNMB) and death. All events were independently adjudicated. Patients were treated with rivaroxaban at a dose of 15 mgpo bid for 3 weeks, followed by 20 mgpo daily for 9 more weeks (minimum 12 weeks).tPa (oralteplase) for management of blocked lines was allowed. Patients were followed clinically for 12 weeks to assess for clinical events including recurrent DVT and/or PE, major bleeding and CRNMB, and by phone at 6 months. Results We included 70 patients (47[67%] women) with a mean age of 54.1 years. DVTs were diagnosed by ultrasound in 68 (97%) patients, and most commonly involved the subclavian (n=55, 79%) and axillary (n=49, 70%) veins, followed by the internal jugular, brachial, brachiocephalic and external jugular veins. Peripherally inserted central catheters (PICC) were most common (n=54, 77%), followed by port-a-cathlines (n=16, 23%). Types of active malignancy included breast (n=29, 41%), colon (n=8, 11%), colorectal (n=5, 7%), rectal (n=3, 4%), prostate (n=1, 1%), and other (n=24, 34%). Catheter survival was 58.6% (95% CI 46.9 to 69.4) at 12 weeks and no catheters were removed due to thrombosis. Patients had their CVCs removed prior to the end of the study due to end of therapeutic need (n=20), infection (n=2), bleeding (n=2), kinking (n=2), patient preference (n=2), and death (n=1). The 3-month incidence rate of recurrent VTE was 1.43% (95% CI 0.25 to 7.66). There was 1 episode of recurrent VTE presenting as a fatal PE at 6 weeks. It was not known if the patient had a concurrent leg DVT at the time of the PE. There were no other deaths from any cause during the study. There were 11 bleeding events in 9 patients (12.85%, 95%CI 6.9 to 22.7), 6 major and 5 CRNMB (Figure 1). All bleeding events happened during the first 39 days of treatment. 7 patients discontinued anticoagulation during the study due to death (n=1), patient or clinician preference (n=5) and dermatological adverse reaction (n=1). Discussion In this study rivaroxaban showed promise in treating CVC-associated UEDVT in cancer patients, resulting in preserved CVC function. However, the bleeding rates and the occurrence of 1 death due to pulmonary embolism is concerning since we cannot exclude a causative role for the known UEDVT. Further studies are still required prior to recommending rivaroxaban in this setting. Figure 1 Kaplan-Meier curve for cumulative bleeding risk. Figure 1. Kaplan-Meier curve for cumulative bleeding risk. Disclosures Lazo-Langner: Daiichi Sankyo: Research Funding; Bayer: Honoraria; Pfizer: Honoraria. Tagalakis:Bayer: Honoraria. Louzada:Celgene: Consultancy, Honoraria; Bayer: Honoraria; Pfizer: Honoraria; Janssen: Consultancy, Honoraria. Kovacs:Bayer: Honoraria, Research Funding; Daiichi Sankyo Pharma: Research Funding; LEO Pharma: Honoraria; Pfizer: Honoraria, Research Funding.

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Identifying Predictors for Bleeding in Hospitalized Cancer Patients: A Cohort Study

Blood ◽

10.1182/blood.v128.22.529.529 ◽

2016 ◽

Vol 128 (22) ◽

pp. 529-529

Author(s):

Rushad Patell ◽

Alejandra Gutierrez ◽

Lisa Rybicki ◽

Alok A. Khorana

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Cohort Study ◽

Length Of Stay ◽

Cancer Patients ◽

Major Bleeding ◽

Research Funding ◽

Bleeding Risk ◽

Bleeding Events ◽

Reason For Admission

Abstract Background: Bleeding and thrombosis are both major complications of hospitalization in cancer patients. We have previously shown that rate of inpatient venous thromboembolism (VTE) is 4% in a general oncology population (Patell et al, ASCO 2016). Concern regarding bleeding risk may reduce compliance with thromboprophylaxis. A better understanding of predictors of bleeding could optimize use of prophylaxis but there remain major knowledge gaps regarding risk factors for in-hospital bleeding in cancer patients. We assessed major and clinically relevant bleeding incidence and identified risk factors at admission associated with subsequent in-hospital bleeding risk in a cohort of hospitalized cancer patients. Methods: We conducted a retrospective cohort study of consecutive adults admitted to general oncology floor at Cleveland Clinic from 2013-14 (n= 3466). Patients were excluded for bleeding on admission (108). Data collected included demographics, body mass index (BMI), cancer type, length of stay (LOS), use of anticoagulants and baseline laboratory values (+48 hours). Bleeding was assessed using the ISTH definitions of major bleeding and clinically relevant non-major bleeding [Schulman 2005 and Decosus 2011]. Data were collected using an electronic query system of electronic health records. Reason for admission and all bleeding events were confirmed by manual chart review. Univariate risk factors were identified with logistic regression analysis. Multivariable risk factors were identified with stepwise logistic regression and confirmed with bootstrap analysis. Results are summarized as odds ratio (OR) and 95% confidence interval (CI). Results: The study population comprised 3,358 patients of whom 69 (2.1%) developed major and clinically relevant non-major bleeding during hospitalization. Median age was 62 (range, 19-98) years and 56% were male. Median length of stay (LOS) was 5 (range, 0-152) days. The majority of bleeding events were either gastrointestinal (N=30, 43%) or intracranial (N= 13, 19%). In univariate analysis, luminal gastrointestinal (GI) cancers (OR 4.2, CI 2.4-7.5, P<0.001), anemia as reason for admission (OR 9.1, CI 5.1-16.4, P<0.001), thrombocytopenia (OR 1.6, CI 1.0-2.6, P=0.046), leukocytosis (OR 2.1, CI 1.2-3.7,P=0.005), low hemoglobin (OR 3.2, CI 1.4-7.1 P=0.003), BMI ≥ 40 kg/m2 (OR 2.6, CI 1.1-5.94, P=0.018) and anticoagulant use on admission (OR 0.4, CI 0.3-0.8, P=0.004) were significantly associated with bleeding. In multivariable analysis, anemia as the reason for admission, primary cancer site, BMI>40, thrombocytopenia and low hemoglobin on admission remained predictive of bleeding (table 1). Conclusion: The incidence of major and clinically relevant bleeding in a large population of hospitalized cancer patients was about 2%, compared to incidence of inpatient VTE in a similar population of 4%. Risk factors at admission included type of cancer and morbid obesity. Improved prediction of bleeding risk can assist physicians in optimizing selection of thromboprophylaxis in this population that is also at increased risk of VTE. Disclosures Khorana: Sanofi: Consultancy, Honoraria; Leo: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria; Halozyme: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Janssen Scientific Affairs, LLC: Consultancy, Honoraria, Research Funding.

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A Prospective Cohort Study of Upper Extremity Deep Vein Thrombosis

Blood ◽

10.1182/blood.v126.23.893.893 ◽

2015 ◽

Vol 126 (23) ◽

pp. 893-893 ◽

Cited By ~ 2

Author(s):

Alejandro Lazo-Langner ◽

Susan R Kahn ◽

Philip S Wells ◽

David Anderson ◽

Marc Rodger ◽

...

Keyword(s):

Cohort Study ◽

Major Bleeding ◽

Research Funding ◽

Survival Curve ◽

Population Characteristics ◽

Vein Thrombosis ◽

Kaplan Meier ◽

Management Protocol ◽

Deep Vein ◽

Meier Survival Curve

Abstract Introduction. Upper extremity deep vein thrombosis (UEDVT) is a relatively uncommon event with potentially serious complications. Its optimal treatment and clinical outcomes are not well studied. The objective of our study was to assess the safety and efficacy of a standardized management protocol for UEDVT as well as its long term complications. Patients and methods. We conducted a prospective cohort study at 5 Canadian centres and enrolled adult patients with a symptomatic UEDVT confirmed by compression ultrasound involving the brachial or more proximal veins, with or without a pulmonary embolism (PE). Exclusions included pregnancy, dialysis catheter thrombosis, active or high bleeding risk, platelet count <100x109/L, creatinine clearance < 30 ml/min, on warfarin for other indications, hemodynamically unstable PE, acute leukemia or undergoing a stem cell transplant within 3 months, geographical inaccessibility, life expectancy <3 months or treatment with low molecular weight heparin (LMWH) or warfarin for more than 7 days since diagnosis. Standardized treatment regimens were as follows: spontaneous or central venous catheter (CVC)-related UEDVT were treated with dalteparin at therapeutic doses for at least 5 days followed by warfarin adjusted according to INR results. Spontaneous UEDVT was treated for at least 6 months and CVC-related events were treated for at least 3 months or for as long as the line remained in place and for at least 1 month after line removal. Cancer patients with non CVC-related UEDVT were treated using dalteparin alone for a minimum of 6 months. Main outcomes were objectively documented venous thromboembolism (VTE) recurrence, major bleeding and death. All outcomes were centrally adjudicated. Patients were followed for 2 years. Data was analyzed using descriptive statistics. Survival data was analyzed using the Kaplan-Meier Method. Post-hoc analyses were conducted comparing CVC and spontaneous events. The study was approved by all institutional review boards. Results. Between 2009 and 2012, we enrolled 141 patients: 75 with spontaneous and 66 with CVC related UEDVT. Mean age was 51 years; 55% were males. The population characteristics are shown in the Table. The 2 year cumulative incidence of VTE recurrence was 3.5% (95% CI 1.5-8), of major bleeding was 2.8% (95% CI 1.1-7.1) and of death was 22% (95% CI 16-29.5). VTE recurrence rate was no different for spontaneous vs. CVC-related groups (4% vs. 3%; Log-Rank P = 0.690; Figure). Conclusion. The use of a standardized management protocol for patients with UEDVT results in a low risk of VTE recurrence and major bleeding at 2 years of follow up, in both CVC-related and spontaneous UEDVT. Table 1. Population characteristics Spontaneous UEDVT Catheter-related UEDVT Total P-value N % N % N % Demographics Age (Mean [SD]) 48.6 [17.8] 54.9 [13.6] 51.6 [16.2] NS Male gender 44 58.7 34 51.5 78 55.3 NS Caucasian 67 89.3 64 97.0 131 92.9 NS Comorbidities Previous VTE 3 4.0 2 3.0 5 3.5 NS Prior or concurrent cancer 22 29.3 48 72.7 70 49.6 <0.001 Prior gastrointestinal Bleeding 6 8.0 5 7.6 11 7.8 NS Type of Catheter NE Hickman - - 1 1.5 1 0.7 PICC - - 49 74.2 49 34.8 Porta Cath - - 16 24.2 16 11.3 Thrombus Location Subclavian 54 72.0 43 65.2 97 68.8 NS Superior vena cava 0 0.0 2 3.0 2 1.4 NS Brachiocephalic 5 6.7 10 15.2 15 10.6 NS Internal Jugular 16 21.3 14 21.2 30 21.3 NS Axillary 39 52.0 34 51.5 73 51.8 NS External Jugular 1 1.3 2 3.0 3 2.1 NS Treatment Duration 3 Months 26 34.7 19 28.8 45 31.9 <0.001 6 Months 37 49.3 4 6.1 41 29.1 0.000 Other 12 16.0 43 65.2 55 39.0 0.000 Figure 1. Kaplan-Meier survival curve for VTE recurrence Figure 1. Kaplan-Meier survival curve for VTE recurrence Disclosures Lazo-Langner: Bayer: Honoraria; Pfizer: Honoraria. Wells:Bayer: Honoraria; BMS/Pfizer: Research Funding. Carrier:BMS: Research Funding; Bayer: Consultancy; Pfizer: Consultancy; LEO Pharma: Consultancy, Research Funding. Kovacs:Bayer: Honoraria, Research Funding; LEO Pharma: Honoraria; Daiichi Sankyo Pharma: Research Funding; Pfizer: Honoraria, Research Funding.

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

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029620979575 ◽

2021 ◽

Vol 27 ◽

pp. 107602962097957

Author(s):

Soo-Mee Bang ◽

Jin-Hyoung Kang ◽

Min Hee Hong ◽

Jin-Seok Ahn ◽

So Yeon Oh ◽

...

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Clinical Outcomes ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Events ◽

Factors Associated ◽

Vein Thrombosis ◽

Medical Chart Review ◽

Deep Vein

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.

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Predicting recurrences or major bleeding in cancer patients with venous thromboembolism

Thrombosis and Haemostasis ◽

10.1160/th08-02-0125 ◽

2008 ◽

Vol 100 (09) ◽

pp. 435-439 ◽

Cited By ~ 105

Author(s):

Javier Trujillo-Santos ◽

José Nieto ◽

Gregorio Tiberio ◽

Andrea Piccioli ◽

Pierpaolo Micco ◽

...

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Cancer Diagnosis ◽

Major Bleeding ◽

Bleeding Complications ◽

Vein Thrombosis ◽

Recurrent Pulmonary Embolism ◽

Acute Venous Thromboembolism ◽

Deep Vein

SummaryCancer patients with acute venous thromboembolism (VTE) have an increased incidence of recurrences and bleeding complications while on anticoagulant therapy. Methods RIETE is an ongoing registry of consecutive patients with acute VTE. We tried to identify which cancer patients are at a higher risk for recurrent pulmonary embolism (PE), deep vein thrombosis (DVT) or major bleeding. Up to May 2007, 3, 805 cancer patients had been enrolled in RIETE. During the first three months of follow-up after the acute, index VTE event, 90 (2.4%) patients developed recurrent PE, 100 (2.6%) recurrent DVT, 156 (4.1%) had major bleeding. Forty patients (44%) died of the recurrent PE,46 (29%) of bleeding. On multivariate analysis, patients aged <65 years (odds ratio [OR]: 3.0; 95% confidence interval [CI]: 1.9–4.9), with PE at entry (OR: 1.9; 95% CI: 1.2–3.1), or with <3 months from cancer diagnosis to VTE (OR: 2.0; 95% CI: 1.2–3.2) had an increased incidence of recurrent PE. Those aged <65 years (OR: 1.6; 95% CI: 1.0–2.4) or with <3 months from cancer diagnosis (OR: 2.4; 95% CI: 1.5–3.6) had an increased incidence of recurrent DVT. Finally, patients with immobility (OR: 1.8; 95% CI: 1.2–2.7), metastases (OR: 1.6; 95% CI: 1.1–2.3), recent bleeding (OR: 2.4; 95% CI: 1.1–5.1), or with creatinine clearance <30 ml/ min (OR: 2.2; 95% CI: 1.5–3.4), had an increased incidence of major bleeding. With some variables available at entry we may identify those cancer patients withVTE at a higher risk for recurrences or major bleeding.

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Prophylactic anticoagulant therapy decreases the incidence of deep vein thrombosis in patients with solid tumors: A systematic review and meta-analysis

Journal of Solid Tumors ◽

10.5430/jst.v7n1p35 ◽

2017 ◽

Vol 7 (1) ◽

pp. 35

Author(s):

Yunjiao Zhou ◽

Gong Yang ◽

Chenglei Huang

Keyword(s):

Systematic Review ◽

Deep Vein Thrombosis ◽

Solid Tumors ◽

Risk Ratio ◽

Major Bleeding ◽

Meta Analysis ◽

Bleeding Events ◽

Vein Thrombosis ◽

And Control ◽

Deep Vein

It is not well understood the efficacy and safety of primary deep vein thrombosis (DVT) prophylaxis of anticoagulants in patients with solid tumors. This systematic review and meta-analysis of randomized controlled trials (RCT) determines the relative ratio of primary DVT, survival rate and bleeding events among patients with solid tumors treated with anticoagulants or placebo. Comprehensive literature searches were conducted through the Pubmed, Ovid MEDLINE and EMBASE databases published from January 1st, 1993 to December 31st, 2015. Statistical analysis was performed by RevMan 5.0 software. For DVT events, therisk ratio in 16 trials between the prophylactic and control patients was statistically significant at 0.45 [0.36-0.58]; for major bleeding events, the risk ratio in 18 trials between the prophylactic and control patients was not statistically significant at 1.33 [0.99-1.79], while that in 15 trials with clinically relevant non-major bleeding was statistically significant at 1.83 [1.46-2.30]; the risk ratio for the mortality rate of patients with solid tumors in 16 trials was not statistically significant at 0.97 [0.93-1.02]. Inconclusion, the risk ratio in this meta-analysis showed a significantly reduced incidence of DVT with anticoagulant use. Treatment to patients who had solid tumors with prophylactic anticoagulants enhanced the incidence rate of non-major bleeding but has no significant impact on the incidence rate of major bleeding. No significant differences were found in the mortality outcomes between anticoagulant and non-anticoagulant groups.

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Antithrombotic Treatment and Outcomes of Splanchnic Vein Thrombosis in an International Prospective Registry: Results of 2-Year Follow-up

Blood ◽

10.1182/blood.v124.21.592.592 ◽

2014 ◽

Vol 124 (21) ◽

pp. 592-592

Author(s):

Walter Ageno ◽

Nicoletta Riva ◽

Sam Schulman ◽

Jan Beyer-Westendorf ◽

Soo-Mee Bang ◽

...

Keyword(s):

Risk Factors ◽

Major Bleeding ◽

Research Funding ◽

Bleeding Events ◽

Primary Analysis ◽

Vascular Events ◽

Vein Thrombosis ◽

Cirrhotic Patients

Abstract Background: Little information is available on the long-term clinical outcome of patients with splanchnic vein thrombosis (SVT). We aimed to assess incidence rates of bleeding, recurrence, and mortality in a large prospective cohort of SVT patients after a 2-year follow-up. Methods: Consecutive SVT patients were enrolled in a multicenter international registry, from 2008 to 2012. Information was gathered on baseline characteristics, risk factors and therapeutic strategies. Clinical outcomes (major bleeding; vascular events, defined as venous or arterial thrombosis, and mortality) during follow-up were collected and reviewed by a Central Adjudication Committee. Major bleeding was defined using the ISTH definition plus the need for hospitalization. The primary analysis was performed up to the first adjudicated major bleeding or thrombotic event. Results: 604 patients from 31 centers were enrolled in this study, 21 (3.5%) were lost to follow-up. Median follow-up duration was 2 years (IQR 1-2). Median age was 54 years (range 16-85); 62.6% were males. Most common risk factors were liver cirrhosis in 27.8% of patients and solid cancer in 22.3%. Portal vein was the most common site of thrombosis. 139 patients were not anticoagulated; 175 received parenteral anticoagulants only (median duration 5.8 months, IQR 3-12) and 290 were started on vitamin K antagonists (median duration 24 months, IQR 7-24). According to the primary analysis, 103 events occurred during follow-up: 35 major bleeding events (3.8/100 patient-years [pt-y]; 95%CI, 2.7-5.2), 2 of which were fatal bleeding, and 68 thrombotic events (7.3/100 pt-y; 95%CI 5.8-9.3), 9 of which were vascular deaths. All-cause mortality occurred in 106 patients (10.3/100 pt-y; 95% CI 8.5-12.5). The incidence of major bleeding events was 4.0/100 pt-y in patients on anticoagulant drugs and 3.4/100 pt-y in patients not receiving anticoagulants. The incidence of vascular events was 5.6/100 pt-y and 9.7/100 pt-y, respectively. Major bleeding and vascular event rates were highest in cirrhotic patients (10.0/100 pt-y and 11.3/100 pt-y, respectively), and lowest in the subgroup of non-malignant non-cirrhotic patients (1.8/100 pt-y and 5.6/100 pt-y, respectively). Conclusions: SVT patients have a non-negligible long-term risk of both bleeding and thrombotic events, but this risk varies according to the pathogenesis of SVT. Anticoagulant treatment is associated with a reduced incidence of thrombotic events without apparently resulting in an increased risk of bleeding. Funding: The study was funded by a grant from Pfizer Canada to ISTH Disclosures Ageno: Bayer Healthcare: Research Funding. Schulman:Bayer HealthCare: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Research Funding. Beyer-Westendorf:Bayer: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Boehringer: Honoraria, Research Funding.

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Subgroup Analysis of Patients with Cancer in Xalia - a Non-Interventional Study of Rivaroxaban in Routine Treatment of Deep Vein Thrombosis

Blood ◽

10.1182/blood.v128.22.1438.1438 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1438-1438 ◽

Cited By ~ 1

Author(s):

Alexander G G Turpie ◽

Lorenzo G Mantovani ◽

Sylvia Haas ◽

Reinhold Kreutz ◽

Danja Monje ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Venous Thromboembolism ◽

Major Bleeding ◽

Research Funding ◽

Incidence Rates ◽

Vein Thrombosis ◽

All Cause Mortality ◽

Recurrent Vte ◽

Deep Vein ◽

Active Cancer

Abstract Background: XALIA is a prospective, non-interventional study of rivaroxaban in the treatment of acute deep vein thrombosis. The overall XALIA results showed that rivaroxaban was associated with similarly low rates of major bleeding and symptomatic recurrent venous thromboembolism (VTE) as standard anticoagulation. A subset of patients in XALIA had active cancer at the time of enrolment into the study. Purpose: To describe the demographics, clinical characteristics, treatment strategies and outcomes of patients in XALIA with cancer and VTE. The primary outcomes were major bleeding, recurrent VTE and all-cause mortality. Methods: Patients with deep vein thrombosis with or without concomitant pulmonary embolism aged ≥18 years who had active cancer and were scheduled to receive ≥3 months of anticoagulation with rivaroxaban or standard therapy were eligible. Therapy type, dose and duration were at the physician's discretion. For the purpose of this substudy, we defined the following treatment cohorts: rivaroxaban cohort (patients treated with rivaroxaban alone or who received heparin/fondaparinux for ≤48 hours before switching to rivaroxaban); early switchers cohort (patients treated with rivaroxaban who received heparin/fondaparinux for >48 hours-14 days and/or a vitamin K antagonist [VKA] for 1-14 days before changing to rivaroxaban); standard anticoagulation cohort (patients treated with heparin/fondaparinux and a VKA or a VKA only); and heparin/fondaparinux cohort (patients treated with heparin/fondaparinux alone). Results: Of 5136 patients in XALIA who received study medication, 587 (11.4%) had active cancer at baseline. Of these, 146 (24.9%) received rivaroxaban, 30 (5.1%) were early switchers, 167 (28.4%) received standard anticoagulation (of which 26 [4.4%] received a VKA only) and 244 (41.6%) received heparin/fondaparinux only, of whom 223 (38.0%) received low molecular weight heparin and the remainder other heparins or fondaparinux. Demographics are shown in Table 1. The most common type of active cancer at baseline in all cohorts was genitourinary, with the exception of the heparin/fondaparinux cohort where gastrointestinal cancer was the most common type (Table 2). The incidence rates for the primary outcomes for each cohort are shown in Figure 1. The rates of major bleeding were highest in the standard anticoagulation cohort (n=8 [4.8%]) and lowest in the early switchers (no major bleeding events occurred). The rates of recurrent VTE were similar in the in the rivaroxaban, early switcher and standard anticoagulation cohorts (n=5 [3.4%], n=1 [3.3%] and n=6 [3.6%], respectively) and were highest in the heparin/fondaparinux cohort (n=12 [4.9%]). All-cause mortality was highest in the heparin/fondaparinux cohort (n=61 [25.0%]) and lowest in the early switchers (no deaths occurred). Conclusions: In the real-world XALIA study, 38.0% of patients with cancer received treatment with low molecular weight heparin, which was in line with guidelines. The remaining patients received rivaroxaban, standard anticoagulation or were early switchers. For the three primary outcomes, the lowest incidence rates were observed in the early switcher cohort. The highest rates were in the standard anticoagulation cohort for major bleeding and the heparin/fondaparinux cohort for recurrent VTE and all-cause mortality; rates for all three primary outcomes were low in the rivaroxaban cohort, suggesting that rivaroxaban may be a safe and effective treatment option for patients with VTE and active cancer. Figure 1 Primary outcomes in patients with active cancer at baseline by treatment group. VTE, venous thromboembolism. Figure 1. Primary outcomes in patients with active cancer at baseline by treatment group. / VTE, venous thromboembolism. Disclosures Turpie: Janssen Research & Development, LLC: Consultancy, Honoraria; Bayer Pharma AG: Consultancy, Honoraria. Mantovani:Janssen-Cilag Ltd: Research Funding; Boehringer Ingelheim: Research Funding; Daiichi Sankyo: Consultancy; Bayer Pharma AG: Consultancy; Pfizer Inc: Research Funding. Haas:Sanofi SA: Consultancy; Pfizer Inc: Consultancy; Daiichi Sankyo: Consultancy; Bristol-Myers Squibb: Consultancy; Bayer Pharma AG: Consultancy; Aspen Pharmacare: Consultancy. Kreutz:Bayer Pharma AG: Honoraria; Servier Laboratories Ltd: Consultancy; Lundbeck Ltd: Consultancy; Daiichi Sankyo: Consultancy; Berlin-Chemie Menarini: Consultancy; Bayer Pharma AG: Consultancy; Bristol-Myers Squibb: Honoraria; Daiichi Sankyo: Honoraria. Monje:Bayer Pharma AG: Employment. Schneider:Bayer Pharma AG: Employment. van Eickels:Bayer Pharma AG: Employment. Gebel:Bayer Pharma AG: Employment. Ageno:Boehringer Ingelheim: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Bayer Pharmaceuticals: Research Funding; Daiichi Sankyo: Consultancy, Honoraria; Bayer Pharma AG: Consultancy, Honoraria.

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Safety of Anticoagulant Therapies for Treatment of Venous Thromboembolism in Patients with Cancer

Blood ◽

10.1182/blood.v128.22.1178.1178 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1178-1178 ◽

Cited By ~ 2

Author(s):

Michael Streiff ◽

Dejan Milentijevic ◽

Keith McCrae ◽

Daniel Yannicelli ◽

Jonathan Fortier ◽

...

Keyword(s):

Cancer Patients ◽

Major Bleeding ◽

Research Funding ◽

Hazard Ratio ◽

Control Cohort ◽

Bleeding Events ◽

Employment Equity ◽

Patients With Cancer ◽

Equity Ownership ◽

Major Bleeding Events

Abstract Introduction: Anticoagulation is effective for the treatment of venous thromboembolism (VTE) in cancer patients, but it is also associated with an increased risk of bleeding. Previous clinical trials (e.g., CLOT and CATCH) of LMWH and warfarin for the treatment of VTE in cancer patients reported major bleeding in 3% to 6% of treated patients. The objective of this observational study was to compare the risk of major bleeding in cancer patients treated with anticoagulants for VTE in a real world setting. Methods: Medical and pharmacy claims from the Humana Database from 1/1/2013 to 05/31/2015 were analyzed. Newly diagnosed cancer patients with a first VTE diagnosis occurring after their first cancer diagnosis, and with ≥1 dispensing of an anticoagulant within 7 days after their VTE diagnosis, were selected. Based on the first anticoagulant received, patients were classified into one of the following cohorts: LMWH, warfarin, and rivaroxaban (other agents not included due to low utilization). Inverse probability of treatment weights based on propensity score were used to adjust for differences between treatment cohorts for the following comparisons: LMWH vs. rivaroxaban, LMWH vs. warfarin, and rivaroxaban vs. warfarin. Patients were followed up until the earliest event, either treatment non-persistence (gap > 60 days between the end of the days of supply of a dispensing and the start date of the next dispensing), or end of data availability. Major bleeding events were identified using validated criteria (Cunningham et al., 2011). Kaplan-Meier rates at 3 and 6 months and Cox proportional hazards models were used to compare the risk of bleeding between different treatment cohorts. To better understand the risk of major bleeding in cancer patients unrelated to anticoagulation, a cohort of patients with cancer who did not have VTE and did not receive an anticoagulant was added as a control cohort. Results: A total of 2,428 patients (LMWH: n=660; warfarin: n=1,061; rivaroxaban: n=707) were included. Baseline demographic and clinical characteristics were well balanced among treatment cohorts. Median duration of therapy with LMWH was shorter than rivaroxaban (1.0 vs. 3.0 months, p<.0001) and warfarin (1.0 vs. 3.5 months, p<.0001). Rates of major bleeding for LMWH and rivaroxaban were 8.3% and 8.2%, respectively at 6 months with a hazard ratio (HRs [95% CI]) of 1.03 (0.64-1.65; Figure 1A). In the comparison between LMWH and warfarin cohorts, major bleeding rates were 8.5% and 8.6%, respectively at 6 months with hazard ratio (HRs [95% CI]) of 1.04 (0.69-1.57; Figure 1B). The risk of major bleeding was also similar for rivaroxaban and warfarin cohorts, 9.0% and 8.7%, respectively at 6 months with a hazard ratio (HR [95% CI]) of 1.01 (0.71-1.43; Figure 1C). For the control cohort of cancer patients without VTE and not receiving anticoagulation median follow-up was 5.6 months. Rates of major bleeding events for the control cohort were 2.6% and 4.2 % at 3 and 6 months, respectively. Conclusion: This real world study of cancer patients treated for VTE found that the risk of major bleeding was similar for the 3 most widely prescribed anticoagulants in current clinical practice: LMWH, warfarin, and rivaroxaban. The observed rates of major bleeding were generally higher than what has been reported for LMWH and warfarin in the CLOT and CATCH trials. Patient characteristics such as older age (average age 73 years) could have contributed to the higher major bleeding rate seen in this study compared to the CLOT and CATCH trials, respectively. Figure 1 Rates of Major Bleeding Events LMWH vs. rivaroxaban cohorts Figure 1. Rates of Major Bleeding Events. / LMWH vs. rivaroxaban cohorts Figure 2 LMWH vs. warfarin cohorts Figure 2. LMWH vs. warfarin cohorts Figure 3 rivaroxaban vs. warfarin cohorts Figure 3. rivaroxaban vs. warfarin cohorts Disclosures Streiff: Portola: Research Funding; Janssen: Consultancy, Research Funding; Roche: Research Funding; CSL Behring: Consultancy, Research Funding. Milentijevic:Janssen Scientific Affairs: Employment, Equity Ownership. McCrae:Janssen: Membership on an entity's Board of Directors or advisory committees. Yannicelli:Janssen Scientific Affairs: Employment, Equity Ownership. Fortier:Janssen Pharmaceuticals: Research Funding. Nelson:Janssen Scientific Affairs: Employment, Equity Ownership. Laliberté:Janssen Scientific Affairs: Research Funding. Crivera:Janssen Scientific Affairs, LLC, Raritan, New Jersey: Employment, Equity Ownership. Lefebvre:Janssen Scientific Affairs: Research Funding. Schein:Johnson & Johnson: Employment, Equity Ownership, Other: Own in excess of $10,000 of J&J stock. Khorana:Roche: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Halozyme: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Leo: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen Scientific Affairs, LLC: Consultancy, Honoraria, Research Funding.

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Bleeding Risk in a Cohort of Ambulatory Cancer Patients Receiving Outpatient Prophylactic Anticoagulation for Venous Thrombosis Prevention

Blood ◽

10.1182/blood-2019-128831 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 709-709

Author(s):

Andrew B Wilks ◽

Daniel Douce ◽

Steven Ades ◽

Mary Cushman ◽

Neil A. Zakai ◽

...

Keyword(s):

Lung Cancer ◽

High Risk ◽

Cancer Patients ◽

Major Bleeding ◽

Bleeding Risk ◽

Bleeding Events ◽

Major Bleed ◽

Prophylactic Dose ◽

Increased Risk ◽

Prophylactic Anticoagulation

Background: Recent clinical trials have evaluated the safety and efficacy of direct oral anticoagulant (DOAC) therapy for venous thromboembolism (VTE) prophylaxis in cancer outpatients at high risk for thrombosis. Bleeding risk in these trials were approximately 2% over the first 6 months of therapy. For individual patients, the utility of prophylactic anticoagulation (AC) depends on an acceptable safety profile between bleeding and thrombosis. We investigated whether ambulatory cancer patients on contemporary cancer-directed therapies and prophylactic AC had an increased risk of major bleeds over the first 6 months of therapy. Methods: As part of a single-center prospective cohort study, we assessed consecutive ambulatory patients initiating cancer-directed treatment, risk-stratified these patients for VTE using the Khorana score and educated them about VTE. High risk patients (Khorana score ≥3) were offered prophylactic AC. Major bleeding events and minor bleeding events (based on ISTH standard definitions) were prospectively captured via billing code screening and confirmed by physician review of the medical record. Logistic regression was used to compare the odds of developing a major bleed within 6 months in those who received prophylactic AC compared to those that did not. Results: A total of 1,210 patients were enrolled from October 2015 - June 2018, of which, 640 were women (52.9%). The most common cancers were gastrointestinal 270 (22%), lung 213 (18%), and breast 198 (16%). There were 393 patients (32%) with a Khorana score of 0, 706 (58%) with a Khorana score of 1-2, and 111 (9%) with a score of ≥3. A total of 421 patients received any AC (LMWH or DOAC). Of these, 282 received a prophylactic dose anticoagulant and 139 were receiving a full dose anticoagulant prior to enrolling for other medical reasons. Prophylactic dose anticoagulants prescribed included apixaban in 107 (41%), rivaroxaban in 6 (2.3%), enoxaparin in 119 (45.7%), and other heparin products in 50 (19.2%). A total of 27 (2.33%) major bleeds and 22 (1.81%) minor bleeds occurred within the first 6 months of starting therapy. Of these bleeding events, 8 (2.8%) occurred in those on prophylactic AC, and 6 (4.3%) occurred in those on full dose AC. The odds ratio (OR) of developing a major bleed on any type of AC was 1.78 [CI 0.817-3.88]. The OR of major bleeding on prophylactic AC was 1.49 [CI 0.64-3.479]. The OR of major bleed was highest in lung cancer patients on prophylactic AC (OR 2.81, CI 1.27-6.25). Men, when compared to women, were more likely to bleed on prophylactic AC in the first six month (OR 0.2; CI 0.07-0.52). The OR for major bleed with each 1 year increase in age was 1.02 (CI 0.99, 1.06). The OR of bleeding with a high risk Khorana score (≥3) compared to a lower score was 1.04 (CI 0.73-1.50). Conclusion: During the first six months of therapy, prophylactic AC was associated with an increased risk of major bleeding events in patients on cancer-directed therapy. In this study, the rate of major bleeding was similar as compared to published clinical trials. Neither age nor higher Khorana score were associated with an increased risk of major bleeds in patients on prophylactic AC. The finding that men, when compared to women, and patients with lung cancer may have an increased risk of major bleeding while on prophylactic AC and cancer-directed chemotherapy suggests these groups may warrant both increased education and monitoring to ensure safety while on prophylactic AC. Disclosures No relevant conflicts of interest to declare.

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The Optimal Duration of Anticoagulant Therapy In Patients with Cancer-Related Deep Vein Thrombosis: The Advantage of Using Residual Vein Thrombosis (the Cancer-DACUS Study)

Blood ◽

10.1182/blood.v116.21.190.190 ◽

2010 ◽

Vol 116 (21) ◽

pp. 190-190 ◽

Cited By ~ 5

Author(s):

Sergio Siragusa ◽

Alessandra Malato ◽

Doris Mascheroni ◽

Walter Ageno ◽

Eugenio Bucherini ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Cancer Patients ◽

Major Bleeding ◽

Recurrent Events ◽

Lower Limbs ◽

Vein Thrombosis ◽

Optimal Duration ◽

Group B ◽

Deep Vein ◽

Active Cancer

Abstract Abstract 190 Type and duration of anticoagulation is still matter of debate in cancer patients with acute Deep Vein Thrombosis (DVT) of the lower limbs. Residual Vein Thrombosis (RVT) has been proven to be effective for assessing the optimal duration of oral anticoagulants in non cancer patients (Siragusa S et al Blood 2008:112:511-5). In the present study we evaluate the role of a RVT-based management of anticoagulation with Low-Molecular Weight Heparin in cancer patients with acute DVT. Materials and Methods. Patients with active cancer and a first episode of DVT were treated with LMWH for 6 months (the first month at full dosage followed by dose reduction of 25% in the next 5 months). At the end of treatment, they were managed according to RVT findings: those with RVT were randomized to continue anticoagulants for 6 additional months (Group A1) or to stop it (Group A2), while patients without RVT stopped LMWH (Group B). Outcomes were recurrent venous thromboembolism and/or major bleeding; patients were followed up for one year after LMWH discontinuation. Results. Over a period of 36 months, 409 patients were evaluated; 62 were excluded (refusal, need for continuing anticoagulation, etc). In total, 347 were included in the study (Table 1). RVT was detected in 242 (69.7%) patients; recurrent events occurred in 21.9% of those randomized to discontinue and 14.2% of those who continued LMWH. In patients without RVT (105, 30.3%), recurrent events occurred in 3 cases (2.8%) (Table 2 and Figure 1). The adjusted Hazard Ratio (HR) for age and sex between RVT groups (Group A2 vs A1) was 1.58 (95% confidence interval [CI], 0.85–2.93; P=.145). The adjusted HR between group A1 versus RVT-negative group (B) was 4.54 (CI 2.3–6.66; P =.028). Five major bleeding events occurred in Group A1 and two events both in Group A2 and B (Table 2). Overall, 89 (25.6%) patients died due to cancer progression after a median follow-up of 10.2 months after heparin withdrawn. Conclusions. The Cancer DACUS is the first ever study evaluating an individual marker for assessing duration of anticoagulation in active cancer population. Final results of the study show that absence of RVT identifies a group of patients at low risk for recurrent thrombosis who can safely stop LMWH after 6 months. Disclosures: No relevant conflicts of interest to declare.

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