Analysis of bleeding risk with concurrent treatment of VEGFR tyrosine kinase inhibitors (TKIs) and factor Xa inhibitors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19305-e19305
Author(s):  
Tiffany L. George ◽  
Sandip H. Patel ◽  
Tzu-Fei Wang ◽  
Sherry Mori-Vogt ◽  
Edmund Folefac ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Major Bleeding ◽  
Kinase Inhibitors ◽  
Metastatic Cancer ◽  
Factor Xa ◽  
Bleeding Risk ◽  
Factor Xa Inhibitors ◽  
Bleeding Events ◽  
Concurrent Treatment ◽  
Clinically Significant

e19305 Background: Tyrosine kinase inhibitors (TKIs) of vascular endothelial growth factor receptor (VEGFR) may interfere with the coagulation system making patients susceptible to both hemorrhage and thromboembolism. Some cancer patients require dual treatment with VEGFR TKIs and factor Xa inhibitors. However, the safety of such combination treatment (e.g. bleeding risk) has not been well characterized in the literature. Methods: This retrospective study identified metastatic cancer patients who received VEGFR TKIs (pazopanib, sunitinib, sorafenib, axitinib, regorafenib, vandetanib, lenvatinib, cabozantinib, tivozanib) and Xa inhibitors (low-molecular weight heparin [LMWH] or direct oral anticoagulants [DOACs]- rivaroxaban or apixaban) from 2001 to 2018 at the Ohio State University. We assessed bleeding risks of dual therapy vs factor Xa inhibitors alone, using the same patients as self-controls. We defined bleeding based on criteria from the International Society on Thrombosis and Haemostasis. Fisher’s exact test was used to compare distribution of bleeding severities and the Cox model was used to analyze bleeding risk. Results: A total of 86 patients were included for analysis, with a median age of 56 (range, 34-88). The patient population was predominantly of male gender (69.7%), Caucasian race (89.3%) and renal cell cancer type (48.9%). As some patients had been on both LMWH and DOAC at different time periods, we found that 81 patients received concurrent TKI and LMWH; 19 patients had concurrent TKI and DOAC. Overall, 25 patients developed 29 clinically significant bleeding events (including 8 major bleeding) during concurrent treatment, and 15 patients developed 17 clinically significant bleeding events (4 major bleeding) during factor Xa inhibitor alone over a median follow up of 63 days. We found a statistically higher bleeding risk with concurrent treatment (HR = 2.23, 95% CI, 1.13–4.42, p = 0.02) compared with Xa inhibitor alone. In a stratified analysis, concurrent VEGFR TKI plus LMWH or DOAC both showed a strong trend for elevated bleeding risk. Although there were increased bleeding events with concurrent treatment, there was no significant difference in the proportion of major bleeding (27.6% vs 23.5%, p = 0.76). Median time to first bleeding event was 56 days for concurrent therapy and 72 days for Xa inhibitor alone. Conclusions: Concurrent treatment of VEGFR TKI and factor Xa inhibitors is associated with significantly increased bleeding risk when compared with factor Xa inhibitors alone in metastatic cancer patients.

scholarly journals Concurrent Treatment of VEGFR Tyrosine Kinase Inhibitors (TKIs) and Factor Xa Inhibitors Is Associated with Increased Bleeding Risks

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3681-3681
Author(s):  
Sandip Patel ◽  
Tiffany George ◽  
Tzu-Fei Wang ◽  
Sherry Mori Vogt ◽  
Edmund Folefac ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Major Bleeding ◽  
Metastatic Cancer ◽  
Bleeding Event ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Factor Xa Inhibitor ◽  
Bleeding Events ◽  
Concurrent Treatment ◽  
Clinically Significant

ABSTRACT Background: Some cancer patients with thromboembolism require dual treatment of VEGFR TKIs and factor Xa inhibitors (direct or indirect), which may contribute to increased bleeding risks. However, the safety of such combination treatment has not been well characterized in the literature or national guidelines. Methods: This is a single center retrospective study, where we identified metastatic cancer patients (renal cancer, colorectal cancer, sarcoma, etc) who received concurrent VEGFR TKIs (pazopanib, sunitinib, sorafenib, axitinib, regorafenib, vandetanib, lenvatinib or cabozantinib) and Xa inhibitors (low-molecular weight heparin [LMWH] or direct oral anticoagulants [DOACs] including rivaroxaban or apixaban) at the Ohio State University Medical Center. We assessed bleeding risks of dual therapies vs. factor Xa inhibitors alone, using the same patients as self controls. We reviewed medical charts of all identified patients for clinically significant bleeding events (defined as combined major bleeding and clinically relevant non-major bleeding by the International Society of Thrombosis and Haemostasis criteria). The Cox proportional hazard model was used to compare the differences of time to first clinically significant bleeding event between the groups of concurrent use and anticoagulant use only. Results: A total of 86 patients (26 females and 60 males) were included: 78 Caucasians, 6 African Americans, and 2 others. 81 patients had concurrent TKI and LMWH treatment; 20 patients had concurrent TKI and DOACs; and 85 patients have had been on factor Xa inhibitor alone (LMWH or DOACs) at some point. Some patients had been on both LMWH and DOACs at different time periods. Overall, there were 29 clinically significant bleeding events (including 8 major bleeding) during concurrent treatment and 17 events (4 major bleeding) during factor Xa inhibitor alone over a median follow up of 63 days (52 days for concurrent treatment and 99 days for Xa inhibitor alone). In this self-control study, concurrent treatment was associated with a statistically higher risk of clinically significant bleeding events (HR, 2.84; 95% CI, 1.43-5.64, P < 0.01), which reached 37% patient population in the first 3 months, while the bleeding associated with factor Xa inhibitor alone seemed spaced out at the entire length of anticoagulation (8% by 6 months). Similar trend was found in the analysis of patient group of concurrent TKI and LMWH vs. LMWH alone (HR, 1.96; 95% CI, 0.95-4.02, P = 0.067), although significance was not reached likely due to insufficient power. Sample size was inadequate for meaningful comparison between concurrent VEGFR TKI and DOAC vs. DOAC alone. Conclusions: Concurrent treatment of VEGFR TKI and factor Xa inhibitors is associated with a significantly increased bleeding risks when compared with factor Xa inhibitors alone in patients with metastatic cancer. Disclosures No relevant conflicts of interest to declare.

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

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 878-878 ◽  
Author(s):  
Gwynivere A Davies ◽  
Alejandro Lazo-Langner ◽  
Esteban Gandara ◽  
Vicky Tagalakis ◽  
Martha L Louzada ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Major Bleeding ◽  
Research Funding ◽  
Venous Catheter ◽  
Bleeding Risk ◽  
Bleeding Events ◽  
Catheter Survival ◽  
Vein Thrombosis ◽  
Kaplan Meier ◽  
Deep Vein

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.

scholarly journals Efficacy and Safety of Direct Oral Factor Xa Inhibitors in 795 Morbidly Obese Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 423-423 ◽  
Author(s):  
Margarita Kushnir ◽  
Yun Choi ◽  
Ruth Eisenberg ◽  
Devika Rao ◽  
Seda Tolu ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Research Funding ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Prescription Date ◽  
Recurrent Vte

Abstract Background: Studies of acute venous thromboembolism (VTE) and non-valvular atrial fibrillation (AF) have shown comparable therapeutic efficacy and similar or lower bleeding risk for direct oral anticoagulants (DOACs) compared to warfarin. Because the representation of morbidly obese patients (BMI ≥40 kg/m2) in pivotal clinical trials has been minimal, efficacy and safety of DOACs in this population are unclear. Our goal was to investigate whether direct oral factor Xa inhibitors, apixaban and rivaroxaban, are as effective and safe as warfarin in morbidly obese (BMI ≥40) patients. Methods: Using our institutional database, we identified all adult patients at Montefiore Medical Center with BMI ≥40 who were started on anticoagulation with apixaban, rivaroxaban or warfarin, for either AF or VTE, between March 1, 2013 and March 1, 2017. We reviewed charts to obtain detailed information on patient demographics and to document clinical outcomes of recurrent VTE, ischemic stroke (CVA) and bleeding from the first prescription date to the earliest of a thrombotic event, discontinuation of medication, death, or June 30, 2017. VTE and CVA episodes were confirmed by imaging (compression sonography, CT scans, ventilation/perfusion scans, MRIs). Bleeding events were classified according to criteria from the Control of Anticoagulation Subcommittee of the International Society on Thrombosis and Haemostasis. Analyses were stratified by anticoagulation indication. Chi-squared tests or Fisher's exact tests were used to assess statistical significance of the differences in VTE, CVA and bleeding rates between anticoagulant cohorts. Differences in times from first prescription date to VTE, CVA and bleeding were analyzed with Kaplan-Meier curves, Log-rank tests, and Cox proportional hazards models. Data were adjusted for age, CHA2DS2-VASc, and Charlson scores. Subgroup analyses were performed for patients with BMI ≥50 kg/m2. Results: Data on 795 patients were collected. In 366 patients with a history of VTE, the rates of recurrent VTE were low and comparable among the apixaban, rivaroxaban and warfarin cohorts [1/47 (2.1%), 3/152 (2%), and 2/167 (1.2%), respectively, p=0.74]. In the subgroup of individuals with BMI ≥50 kg/m2 (n=92), none of the 40 DOAC patients had recurrent VTE. The rates of clinically relevant bleeding, including major bleeding, among VTE patients, were comparable between the three cohorts. Among the 429 patients with AF, stroke rates were also low and similar among anticoagulant cohorts [1/103 (1%) for apixaban, 4/174 (2.3%) for rivaroxaban, and 2/152 (1.3%) for warfarin, p=0.71]. CVAs were similarly rare in patients with BMI ≥50 (1/19 patients on apixaban, 0/37 on rivaroxaban and 1/44 patients on warfarin). In the AF sample, there was no statistically significant difference in the rate of bleeding, including major bleeding, among the 3 cohorts. In an analysis with combined DOAC cohort (apixaban + rivaroxaban vs. warfarin), the recurrent VTE and stroke rates were still low and comparable. There were more major bleeding events in AF patients on warfarin than the combined DOAC cohort (7.9% vs. 2.9%, p=0.02), a finding that became non-significant when adjusted for age, CHA2DS2-VASc, and Charlson scores (p=0.06). The rates of bleeding, including major bleeding, were comparable among the three anticoagulants in both VTE and AF patients with BMI ≥50. Conclusions: Our study is the largest study examining morbidly obese patients on DOACS and provides further evidence of comparable efficacy and safety of the direct oral anti-Xa inhibitors, compared to warfarin, in morbidly obese patients with AF and VTE. Disclosures Kushnir: Janssen: Research Funding. Billett:Bayer: Consultancy; Janssen: Research Funding.

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

Blood ◽  
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.

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

Blood ◽  
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.

Clinical Impact and Course of Anticoagulant-Related Major Bleeding in Cancer Patients

2018 ◽  
Vol 118 (01) ◽  
pp. 174-181 ◽  
Author(s):  
Noémie Kraaijpoel ◽  
Nick van Es ◽  
Suzanne Bleker ◽  
Marjolein Brekelmans ◽  
Elise Eerenberg ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Major Bleeding ◽  
Clinical Presentation ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Factor Xa ◽  
Phase Iii ◽  
Bleeding Events ◽  
Increased Risk ◽  
Major Bleeding Events

AbstractCancer patients with venous thromboembolism (VTE) have a two- to six-fold increased risk of anticoagulant-related major bleeding events compared with VTE patients without cancer. It is unknown whether major bleeding events are more severe in cancer patients than in those without cancer. Individual patient data from four randomized phase III trials that compared factor Xa inhibitors and vitamin K antagonists for the treatment of VTE were used to compare the severity of major bleeding events in patients with and without cancer. Using predefined criteria, the severity of the clinical presentation and course of major bleeding events were classified into four categories of increasing severity. A one-stage meta-analysis was used to evaluate the effect of cancer on the severity of the clinical presentation and course by estimating crude odds ratios (ORs) and ORs adjusted for age, sex and anticoagulant type with 95% confidence intervals (CIs). The study group comprised 290 patients with major bleeding, of whom 50 (17%) had cancer. The clinical presentation was judged to be severe (category 3 or 4) in 38% of patients with cancer and 44% of patients without cancer (adjusted OR, 0.90; 95% CI, 0.47–1.72). The clinical course was found to be severe in 20 and 25% of patients with and without cancer, respectively (adjusted OR, 0.75; 95% CI, 0.35–1.61). The present study suggests that the clinical presentation and course of anticoagulant-related major bleeding events are not more severe in cancer patients than in patients without cancer. This may be reassuring for physicians who treat cancer patients with anticoagulant-related bleeding.

scholarly journals The Real World Experience Regarding the Safety of Rivaroxaban and Apixaban in Venous Thromboembolism Patients with High Bleeding Risk

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4927-4927
Author(s):  
Haoxu Ouyang ◽  
Ratesh Khillan ◽  
Nyein Htway Yu ◽  
Mohan Preet
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Real World ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Bleeding Risk ◽  
Bleeding Events ◽  
Heparin Group ◽  
Bleeding Rate ◽  
High Bleeding Risk

Background Rivaroxaban and apixaban are two direct oral anticoagulants (DOACs) targeting Factor Xa. Each DOAC was separately proven effective and safe when compared to standard treatment (heparin followed by warfarin) in patients diagnosed with venous thromboembolism (VTE). Several retrospective cohort analyses suggest apixaban may be superior to rivaroxaban due to less bleeding rates. One recent study showed the safety of apixaban and rivaroxaban for acute VTE were comparable. Also, long-term anticoagulation with low molecular weight heparin (LMWH), has never been directly compared with Factor Xa inhibitors. Given the patient population at our facility includes a significant percentage of elderly from nursing homes with multiple comorbidities and significantly higher bleeding risks than the general population, we aimed to evaluate the local real-world DOACs and heparin use with particular focus on safety. Methods A retrospective study was conducted at Kingsbrook Jewish Medical Center. Demographics, relevant laboratory/ imaging studies for patients admitted from 1/2016 to 12/2018 with the diagnosis of VTE based on the ICD 9/10 codes were collected from the IT dept. VTE patients who had bleeding events during the same admission for VTE or were admitted for relevant bleeding events based on ICD 9/10 codes within 6 months from the diagnosis of VTE were identified. Major bleeding events were defined as requiring hospitalization, blood transfusion or a significant drop in hemoglobin (more than 2 g/dl). The rest of the bleeding events were classified as minor. Demographics and clinical characteristics were summarized with means/median for continuous variables and with proportions for categorical variables. The differences in covaries were assessed with chi-square, Fisher exact test or t-tests. Results A total of 177 acute VTE patients were identified in the study. 37.9% (n=67) and 32.8% (n=58) patients were started on rivaroxaban and apixaban, respectively, as monotherapy. 29.3% (n=52) patients were given unfractionated heparin (23%, n=12) or LMWH (77%, n=40) based on the renal function. The bleeding rate in the apixaban group (4/58, 6.9%) was slightly higher than that in the rivaroxaban group (3/67, 4.5%), however, there was no statistical significance. Compared to patients received heparin (11/52, 21.2%), patients started on rivaroxaban (p=0.008) or apixaban (p=0.049) had a significantly lower rate of bleeding. Of note, majority of the bleeding event (16/18) was captured during the same admission when VTE was diagnosed. VTE patients in the apixaban group were older (p = 0.007) and had a longer length of stay (LOS, p= 0.024) compared to the ones in the rivaroxaban group. We then combined rivaroxaban and apixaban into DOAC group. Compared to Heparin group (n=11, 21.1%), the bleeding events in DOAC group (n=7, 5.6%) were significantly less (P=0.0045). Heparin group (n=21, 40.4%) included more patients with cancer than the DOAC group (n=9, 7.2%, p <0.0001), suggesting active malignancy may be correlating with higher bleeding risk. We then looked at the bleeding risk in non-cancer patients. Similarly, we didn't observe any superiority between rivaroxaban (n=2, 3.1%) and apixaban (n=3, 5.8%) regarding bleeding events in non-cancer patients with acute VTE. The average LOS in the apixaban group was significantly longer than that in the rivaroxaban group with non-cancer patients. It may be associated with relatively older age in the apixaban group compared to that in the rivaroxaban group. Most importantly, in patients without active malignancy, we found that the bleeding rate in the DOAC group was only 4.3% while the heparin group had a much high bleeding rate of 16.1% (p=0.035). Discussion Our study suggested that the safety of apixaban and rivaroxaban are comparable in VTE patients. In contrast, heparin including LMWH had much higher bleeding risk compared to either DOAC, especially in the beginning. For patients who are hospitalized for acute VTE, heparin intravenously or subcutaneously are usually initiated while the decision for oral anticoagulants are still pending. However, the benefits of such "bridging with heparin" strategy are not warranted, given the high bleeding risk associated with heparin treatment as shown in our study. Except for hemodynamically instability, excessive burden or clots, or impeding procedures, we recommend that DOACs should be used as monotherapy in VTE patients. Disclosures No relevant conflicts of interest to declare.

Acute coronary syndrome patients with two minor high-bleeding risk criteria have the same bleeding rate that patients with one major criteria

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Cordero ◽  
J.M Garcia-Acuna ◽  
M Rodriguez-Manero ◽  
B Cid ◽  
B Alvarez Alvarez ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Academic Research ◽  
Bleeding Risk ◽  
Bleeding Events ◽  
Post Discharge ◽  
Bleeding Rate ◽  
Coronary Syndrome ◽  
All Cause Mortality ◽  
High Bleeding Risk ◽  
Minor Criteria

Abstract Background In 2019 the Academic Research Consortium of high-bleeding risk (ARC-HBR) proposed a new and binary definition of high-bleeding risk (HBR) patients based on the presence of 1 major or 2 minor criteria. Methods Prospective study of all consecutive patients admitted for ACS in two different centers. We analyzed bleeding incidence in patients with 1 major criteria (1MC) vs. 2 minor criteria (2mC) using the 2019 ARC-HBR consensus. Bleeding events were collected according those fitting definitions 3 or 5 of the BARC consortium. Results We included 8,724 patients included and 40.9% we classified as HBR; 20.9% for 1MC and 20.0% for 2mC. In-hospital mayor bleeding rate was 8.6%; no-HBR patients had 0.3%, 2mC 15.1% and 1MC 29.7% (p&lt;0.001 for the comparison). In contrast, the statistically highest in-hospital mortality was observed in patients with 2mC (11.4%), followed by patients with 1MC (8.0%) and no-HBR patients (2.0%). During follow-up (median time 57.8 months) all-cause mortality rate was 21.0% and cardiovascular dead 14.2%. The incidence of post-discharge major bleeding was 10.5%. No-HBR patients had the lowest bleeding rate (7.4%) and no difference was observed in patients with 1MC (14.6%) or 2mC (15.8%) (figure). The multivariate analysis, adjusted by age, gender, medical treatment, atrial fibrillation and revascularization and considering all-cause mortality as competing risk, showed independent association of 1MC (sHR: 1.46, 95% 1.22–1.75) and 2mC (sHR: 1.31, 95% CI 1.05–1.63) with post-discharge major bleeding. Conclusions HBR patients according to the 2019 ARC-HBR containing 2mC or 1MC are at similar and higher risk of in-hospital or post-discharge bleeding events Funding Acknowledgement Type of funding source: None

scholarly journals Bleeding Risk in Non-Valvular Atrial Fibrillation Patients Receiving Direct Oral Anticoagulants and Warfarin: A Systematic Review and Meta-Analysis of Observational Studies

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3672-3672 ◽  
Author(s):  
Yimin Pearl Wang ◽  
Rohan Kehar ◽  
Alla Iansavitchene ◽  
Alejandro Lazo-Langner
Keyword(s):  
Major Bleeding ◽  
Lower Risk ◽  
Observational Studies ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Bleeding Risk ◽  
Risk Of Bleeding ◽  
Significant Difference

Introduction: The standard oral anticoagulant therapy administered to non-valvular AF patients has typically been Vitamin K Antagonists (VKA) particularly warfarin. In recent years, Direct Oral Anticoagulants (DOACs) including Direct Thrombin Inhibitors (DTI) and Direct Factor Xa inhibitors (FXa inhibitors) have become an alternative to warfarin. Randomized trials comparing warfarin and DOACs showed comparable effectiveness without significant additional major bleeding risk. However, bleeding events in RCTs may differ from those in daily use due to the routine exclusion of patients with a higher risk of bleeding from many studies. We aimed to assess bleeding risk between DOACs and warfarin in AF patients in observational studies and we also sought to determine differences between patients that were experienced or naïve to oral anticoagulants. Methods: A systematic literature search was conducted in the OVID MEDLINE® and EMBASE® electronic databases. Observational studies and randomized control trials (RCT) from 1990 to January 2019 were retrieved and examined by two independent reviewers. A pooled effect hazard ratio (HR) was calculated using a random effects model using the generic inverse variance method. Subgroup analyses according to previous exposure to anticoagulants, study type, funding type and DOAC type were conducted. The primary outcome was major bleeding risk. The secondary outcome was clinically relevant non-major bleeding. All studies must have used an established or validated definition of major bleeding. Results: The initial literature search identified 3359 potentially eligible citations. After primary screening, 150 articles were eligible for full text review and there were 35 studies including 2,356,201 patients that met the inclusion criteria. Overall, patients on DOACs were less likely to experience a bleeding event compared to warfarin (HR 0.78, 95%CI 0.71, 0.85, P&lt;0.001). The results were consistent when analyzing patients receiving DTIs or FXa inhibitors (DTI: HR 0.76, 95% CI 0.67,0.87; FXa inhibitors: HR 0.79, 95% CI 0.69,0.89). However, among patients receiving factor Xa inhibitors, there was a significant difference in the risk of bleeding according to individual drug. Among patients receiving rivaroxaban the risk of bleeding was similar to warfarin (HR 0.98, 95%CI 0.91,1.06, p=0.60) whereas in those receiving apixaban there was a 40% reduction in the risk of bleeding compared to warfarin (HR 0.60, 95%CI 0.50,0.71, p&lt;0.001) (Figure 1). Three studies reported information according to previous anticoagulant exposure. The overall pooled hazard ratio was 0.68 (95% CI 0.55, 0.82 p&lt;0.001) in favor of patients on DOACs. In the subgroup analysis of previous anticoagulant use, the risk of bleeding was lower for DOACs compared to warfarin in both the experienced population (HR 0.70, 95%CI 0.51, 0.96) and the naïve population (HR 0.64, 95% CI 0.47,0.87). However, heterogeneity was moderate to high among both subgroups. Conclusion: This review and meta-analysis of observational studies including over 2.3 million patients showed that overall DOACs have a lower risk of major bleeding and clinically relevant non-major bleeding compared to warfarin. Most importantly, although the pooled effect estimate did not differ between DTIs and FXa inhibitors, among patients receiving FXa inhibitors there was a significant difference between individual agents. Patients on apixaban had a significantly lower risk of bleeding compared to warfarin in contrast to patients on rivaroxaban who had a similar risk. Disclosures No relevant conflicts of interest to declare.

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