P5593The association of recurrence and bleeding events with mortality after venous thromboembolism: from the COMMAND VTE Registry

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Yamashita ◽  
Y Yoshikawa ◽  
T Morimoto ◽  
H Amano ◽  
T Takase ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Mortality Risk ◽  
Cox Model ◽  
Anticoagulation Therapy ◽  
Bleeding Events ◽  
Cox Proportional Hazard ◽  
Recurrent Vte ◽  
Major Bleeding Events ◽  
The Impact

Abstract Background/Introduction Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), has a long-term risk for recurrence, which can be prevented by anticoagulation therapy. The duration of anticoagulation therapy after VTE should be based on the balance between risks of recurrent VTE and bleeding. However, there is uncertainty about the impact of these events on subsequent mortality. Purpose We sought to evaluate the impact of recurrent VTE events and bleeding events on subsequent mortality in patients with VTE in a large retrospective observational database in Japan. Methods We evaluated the association of recurrent VTE and major bleeding with mortality among 3026 patients in the COMMAND VTE Registry. We estimated the risks of recurrent VTE events and major bleeding events for subsequent all-cause death with the multivariable Cox proportional hazard model. We incorporated the recurrent VTE events and major bleeding events during follow-up into the multivariable Cox model as time-updated covariates together with the clinically-relevant 16 risk-adjusting factors. We expressed the adjusted risks of each covariate as hazard ratios (HR) and their 95%confidence intervals (CI). Furthermore, to assess the risks of recurrent PE and recurrent DVT events for subsequent all-cause death respectively, we divided recurrent VTE events into recurrent PE (PE with or without DVT) and recurrent DVT (DVT only), and incorporated these events as well as major bleeding events into the multivariable Cox model as time-updated covariates. Results In the current study population, the mean age was 67 years, 61% were women, and mean body weight and body mass index were 57.9 kg and 23.2 kg/m2, respectively. During the median follow-up period of 1,218 days, 763 patients died, 225 patients developed recurrent VTE events, and 274 patients developed major bleeding events. The time-updated multivariable Cox proportional hazard model revealed that both the recurrent VTE events and the major bleeding events were strongly associated with subsequent mortality risk (recurrent VTE events: HR 3.24, 95% CI 2.57–4.08, P<0.001; major bleeding events: HR 3.53, 95% CI 2.88–4.31, P<0.001). Both the recurrent PE events and the recurrent DVT events were associated with subsequent mortality risk with the numerically greater magnitude of effect with the recurrent PE events than with the recurrent DVT events (recurrent PE events: HR 4.42, 95% CI 3.28–5.95, P<0.001; recurrent DVT events: HR 2.42, 95% CI 1.75–3.36, P<0.001). Conclusions In the real-world patients with VTE, both recurrent VTE events and major bleeding events were strongly associated with subsequent mortality risk with the comparable effect size. Recurrent PE and recurrent DVT events were also associated with increased risks for mortality, although the magnitude of the effect on mortality was numerically greater with the recurrent PE events than with the recurrent DVT events. Acknowledgement/Funding Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation

scholarly journals Case Fatality Rate of Recurrent Venous Thromboembolism and Major Bleeding Events Among Patients Treated for Cancer-Associated Venous Thromboembolism: A Systematic Review

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2528-2528 ◽  
Author(s):  
Alym Abdulla ◽  
Wendy Davis ◽  
Namali Ratnaweera ◽  
Brooke Scott ◽  
Agnes Yuet Ying Lee
Keyword(s):  
Major Bleeding ◽  
Research Funding ◽  
Case Fatality Rate ◽  
Case Fatality ◽  
Controlled Trials ◽  
Bleeding Events ◽  
Patients With Cancer ◽  
Recurrent Vte ◽  
Major Bleeding Events

Abstract Background Venous thromboembolism (VTE) is a major cause of morbidity and mortality in patients with cancer. Despite therapeutic anticoagulation, the risks of recurrent VTE and major bleeding are approximately 10% and 5%, respectively, during the first 6 months of treatment. Overall mortality ranges from 25% to 40%, depending on the study population. Knowing the case fatality rates of these outcomes is also important for weighing the relative risks and benefits of anticoagulation in patients with cancer-associated VTE but these rates have not been reported previously. Objective To determine the incidence of recurrent VTE and major bleeding events and to calculate the case fatality rates of these outcomes in patients undergoing anticoagulation for cancer-associated VTE. Methods An electronic search of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials from January 1980 to May 2018 was performed. English language publications (observational studies and randomized controlled trials [RCTs]) that reported on patients with active cancer and VTE who received anticoagulation with low molecular weight heparin (LMWH), vitamin K antagonist (VKA), or a direct oral anticoagulant (DOAC) for at least 3 months were retrieved for review. In addition, a hand search of references of review articles was done to complement the electronic literature search. Studies that provided information on recurrent VTE, major bleeding events, mortality, and causes of death were included in analyses. Retrospective studies and prospective cohorts with fewer than 50 patients were excluded. Two reviewers independently screened for study eligibility and extracted data onto standardized forms. Study outcomes were recurrent VTE, major bleeding and death. Pooled proportions with 95% confidence intervals (CI) were calculated according to anticoagulant treatment and study design. Results The search identified 7327 studies of which 29 studies (15 prospective cohort studies and 14 randomized controlled trials) were included. Data from 8000 cancer patients followed for a total of 4786 patient-years (range 3 to 36 months) were summarized. The rate of recurrent VTE and fatal recurrent VTE were 15.7% (95% CI, 14.4% to 17.1%) and 2.5% (95% CI, 2.0% to 3.0%) per patient-year of follow-up, respectively, with a case fatality rate of 15.8% (95% CI, 12.7% to 18.8%). A sub-analysis revealed case fatality rates for recurrent VTE to be 16.3% (95% CI, 12.2% to 20.4%) for LMWH, 20.4% (95% CI, 14.0% to 26.8%) for VKA, and 10.8% (95% CI, 3.2% to 18.3%) for DOAC therapies. The rate of major bleeding and fatal major bleeding events were 6.4% (95% CI, 5.5% to 7.3%) and 1.2% (95% CI, 0.8% to 1.6%) per patient-year of follow-up, respectively, with a case fatality rate of 12.3% (95% CI, 8.7% to 15.9%). A sub-analysis revealed case fatality rates for major bleeding events to be 14.9% (95% CI, 9.6% to 20.2%), 27.9% (95% CI, 14.5% to 41.3%), and 1.9% (95% CI, 0% to 5.5%) for LMWH, VKA, and DOAC therapies, respectively. Among RCTs, case fatality for recurrent VTE was 17.3% (95% CI, 13.5% to 21.2%) and for major bleeding was 10.8% (95% CI, 3.2% to 18.3%). Among prospective cohort studies, respective case fatality rates were 12.8% (95% CI, 8.0% to 17.5%) and 15.3% (95% CI, 8.6% to 22.0%). Studies were heterogeneous in the duration of follow up and their reporting of the causes of death and definition of fatal PE. Conclusion The incidences of recurrent VTE and major bleed events are high in patients with cancer-associated VTE on anticoagulant therapy. Case fatality from recurrent thrombosis is higher than the case fatality from major bleeding. Differences among various anticoagulants likely reflect patient selection bias and heterogeneity of studies. Disclosures Lee: BMS: Research Funding; Bayer: Consultancy, Honoraria; LEO Pharma: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Servier: Honoraria.

Risk Factors for Major Bleeding during Prolonged Anticoagulation Therapy in Patients with Venous Thromboembolism: From the COMMAND VTE Registry

2019 ◽  
Vol 119 (09) ◽  
pp. 1498-1507 ◽  
Author(s):  
Kitae Kim ◽  
Yugo Yamashita ◽  
Takeshi Morimoto ◽  
Takeshi Kitai ◽  
Takafumi Yamane ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Acute Phase ◽  
Major Bleeding ◽  
Anticoagulation Therapy ◽  
Bleeding Events ◽  
Increased Risk ◽  
Major Bleeding Events ◽  
Active Cancer

Background There are limited data assessing the risk for bleeding on anticoagulation therapy beyond the acute phase in patients with venous thromboembolism (VTE). The present study aimed to identify risk factors for major bleeding during prolonged anticoagulation therapy in VTE patients. Patients and Methods The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTE. The current study population consisted of 2,728 patients who received anticoagulation therapy beyond the acute phase, after excluding those patients with major bleeding events (n = 48), death (n = 66), or loss to follow-up (n = 32) during the initial parenteral anticoagulation period within 10 days after diagnosis, and those without anticoagulation therapy beyond 10 days after diagnosis (n = 153). Results During the median follow-up period of 555 days, major bleeding occurred in 189 patients (70 patients within 3 months; 119 patients beyond 3 months) with fatal bleeding in 24 patients (13%). The cumulative incidence of major bleeding was 2.7% at 3 months, 5.2% at 1 year, and 11.8% at 5 years. Active cancer (hazard ratio [HR], 3.06, 95% confidence interval [CI], 2.23–4.18), previous major bleeding (HR, 2.38, 95% CI, 1.51–3.59), anemia (HR, 1.75, 95% CI, 1.27–2.43), thrombocytopenia (HR, 2.11, 95% CI, 1.27–3.33), and age ≥75 years (HR, 1.64, 95% CI, 1.22–2.20) were independently associated with an increased risk for major bleeding by the multivariable Cox regression model. Conclusion Major bleeding events were not uncommon during prolonged anticoagulation therapy in real-world VTE patients. Active cancer, previous major bleeding, anemia, thrombocytopenia, and old age were the independent risk factors for major bleeding.

scholarly journals Outcomes in the Secondary Prevention of Cerebral Venous Thrombosis in Cancer Only Population

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5063-5063
Author(s):  
Nadia Isabel Abelhad
Keyword(s):  
Venous Thrombosis ◽  
Major Bleeding ◽  
Cerebral Venous Thrombosis ◽  
Conflicts Of Interest ◽  
Anticoagulation Therapy ◽  
Categorical Variables ◽  
Fisher Exact Test ◽  
Bleeding Events ◽  
Major Bleeding Events ◽  
The Impact

Abstract BACKGROUND AND PURPOSE: There are scant data on the outcomes of cerebral venous thrombosis (CVT) in the cancer only population. Current anticoagulation guidelines exist for the general population but the effect of these strategies in cancer subgroups are not known. We examined the clinical outcomes such as recanalization, thrombosis recurrence and major bleeding during cerebral venous thrombosis treatment in an exclusively cancer population. METHODS: A retrospective cohort study of cancer only patients with cerebral venous thrombosis identified through an institutional data warehouse at MD Anderson Cancer Center between January 2002 and June 2017. Patients with other indications for long term anticoagulation, chronic cerebrovascular thrombosis or less than 12 month follow up were excluded from the primary analysis. The primary end point was thrombus recanalization. Secondary end points were major bleeding and recurrence of cerebral or venous thrombosis. Demographic data, cancer diagnosis and cancer-therapy was also obtained at the time of initial CVT for further analysis. Chi-square test or Fisher exact test were used to assess the association between categorical variables. RESULTS: The population comprised predominantly male adults (55.6%) with median age 54.5 years, IQR [41.5 to 62.4]. The underlying malignancies were non-hematologic in 64.4% of cases. Anticoagulation was used in the treatment of 73.3% of cases, predominantly low molecular weight heparin (LMWH), and a median duration of 7.9 months, IQR [3.1 to 30.8]. Partial and complete recanalization were achieved in 33.3% and 17.8% of cases, respectively. The CVT recurrence rate at 12 months was 15.6% and 31% of patients suffered major bleeding. Most of the major bleeding events (71.1%) occurred outside the brain. Anticoagulation therapy with LWMH showed a trend to a higher rate of thrombus recanalization (p=0.196) without an increment in the overall bleeding events. We observed a lower rate of major bleeding events in patients treated with LWMH when compared with oral anticoagulation (5/14 versus 18/31, respectively; p=0.049). CONCLUSIONS: Our findings suggest that LMWH might represent an effective and safe strategy for the management of CVT in cancer patients. The findings are consistent with results from large randomized trials for outcomes of cancer associated venous thrombosis in other anatomical locations. The impact of thrombus recanalization in recurrent thrombosis and bleeding outcomes deserves further exploration. Limitations to our study are the retrospective and non-randomized design for the adjudication of treatment agents. Disclosures No relevant conflicts of interest to declare.

Pattern and Management of ISTH Major Bleeding Complications with Direct Oral Anticoagulants - Results of the Prospective Dresden Noac Registry (NCT01588119)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 892-892 ◽  
Author(s):  
Sandra Marten ◽  
Luise Tittl ◽  
Katharina Daschkow ◽  
Jan Beyer-Westendorf
Keyword(s):  
Major Bleeding ◽  
Research Funding ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Red Blood Cell Transfusion ◽  
Bleeding Complications ◽  
Bleeding Events ◽  
Major Bleeding Events ◽  
The Impact

Abstract Background: The most common side effects of oral anticoagulants are bleeding complications. In large trials, direct oral anticoagulants (DOAC) have been shown to reduce the risk of major bleeding compared to warfarin. However, little is known about the management and outcome of survivors of major DOAC bleeding. Patients and methods: Using data from the prospective, non-interventional Dresden NOAC registry, we evaluated the management and outcome of survivors of major DOAC bleeding. All DOAC bleeding complications were centrally adjudicated and classified according to ISTH definition. For this analysis, every ISTH major bleeding was identified in the database and for each case, the first major bleeding was evaluated. Restart of oral anticoagulation (OAC) 30 days after major DOAC bleeding was assessed and the impact of restart on the composite endpoint of (recurrent major bleeding, stroke, TIA, systemic embolism, venous thromboembolism) or survival was evaluated using Kaplan-Meier time-to-first event estimation. Results: Until January 31th 2015, 2771 patients were enrolled into the registry (1898 treated with rivaroxaban, 525 apixaban and 348 dabigatran). During follow-up (mean follow-up duration 23.6 months) 127 patients developed 170 ISTH major bleeding events during DOAC exposure (drop of hemoglobin ≥2g/l in 106 (62.4%) cases, transfusion of ≥2 units of red blood cells in 105 (61.8%) cases, critical site bleeding in 43 (25.3%) cases and/or fatal outcome in 9 cases (5.3%)). Of the 127 patients with major bleeding (mean age 77±11 years; range 37-94), 53.5% were male the median HAS-BLED score was 2 (25th/75th percentile 1/2, range 0-5). The majority major bleeding events occurred spontaneously (64.6%). In contrast, 14.2% major bleeding events occurred after trauma and 21.3% occurred after surgical or interventional procedures that were performed during treatment or within 3 days after last DOAC intake. Most common sites of bleeding were gastrointestinal tract (37%), diffuse bleeding during or after surgery (15.7%), intracranial (11%), skin/mucosal (9.4%), intraocular (8.7%), genitourinary (7.9%), intraarticular bleeding (6.3%) and bleeding in other sites (4%). 85 cases lead on to a hospitalization (mean duration 9±7d) and 11 cases were managed as outpatient. The remaining 31 bleeding events occurred during a hospital stay. The majority of cases were managed with surgical or interventional treatment (55.9%; mainly endoscopic treatment for gastrointestinal bleeding. In 75 (57.1%) cases red blood cell transfusion was given and 11 (8.7%) of cases received fresh frozen plasma. Furthermore, 15 (11.8%) of cases received PCC and 4 (3.1%) fibrinogen. The restart of OAC (DOAC or vitamin K antagonists; VKA) was assessed at day 30 after major bleeding. While OAC was restarted in 80 patients (63%) it was not restarted 30 days after bleeding in the remaining 47 (37%). Patients who restarted OAC had a similar mean age (76 vs. 78y, p=0.309) and a similar mean HAS-BLED score (1.8 vs. 2.1, p=0.115) compared to patients who did not restart OAC. During follow up after bleeding (mean follow-up duration 15.2 months), the rate of combined endpoint of recurrent major bleed and thromboembolism was significantly lower in patients that restarted OAC compared to those who did not restart (14.7/100 patient years; 95%-CI 8.0-24.7 vs. 38.6/100 patient years; 21.1-64.7; p=0.0342). All-cause mortality was found to be 23.9/100 patient years (95% CI 16.9-32.8). Mortality was significantly lower in patients that restarted OAC compared to those who did not restart (16.4/100 patient years [9.7-25.9] vs. 40.6/100 patient years [24.8-62.7]; p=0.0099). Most common cause of death was fatal cardiovascular event (12/38, 31.6%) and fatal bleeding (9/38, 23.7%) followed by terminal malignant disease (6/38, 15.8%), infection/sepsis (6/38, 15.8%) and age related death (5/38, 13.2%). Conclusion: Even in cases with major DOAC bleeding, acute mortality is low with a case-fatality rate of 5.3%. Furthermore, OAC is restarted within 30 days after major bleeding in only 63%. Patients who restarted OAC had significantly lower rates of the combined endpoint of thromboembolism or recurrent major bleeding and had a significantly better survival. Therefore, benefits of OAC continuation may outweigh the risks even in patients with major DOAC-related bleeding. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Marten: Bayer HealthCare: Honoraria. Beyer-Westendorf:Bayer HealthCare: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Bristol- Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding.

A Systematic Review of Anticoagulation Strategies for Patients With Atrial Fibrillation in Critical Care.

2021 ◽  
Author(s):  
Alexandra Jayne Nelson ◽  
Brian W Johnston ◽  
Alicia Achiaa Charlotte Waite ◽  
Gedeon Lemma ◽  
Ingeborg Dorothea Welters
Keyword(s):  
Atrial Fibrillation ◽  
Critical Care ◽  
Critically Ill ◽  
Major Bleeding ◽  
Critically Ill Patients ◽  
Thromboembolic Events ◽  
Bleeding Events ◽  
Major Bleeding Events ◽  
The Impact ◽  
Anticoagulated Patients

Background. Atrial fibrillation (AF) is the most common cardiac arrhythmia in critically ill patients. There is a paucity of data assessing the impact of anticoagulation strategies on clinical outcomes for general critical care patients with AF. Our aim was to assess the existing literature to evaluate the effectiveness of anticoagulation strategies used in critical care for AF. Methodology. A systematic literature search was conducted using MEDLINE, EMBASE, CENTRAL and PubMed databases. Studies reporting anticoagulation strategies for AF in adults admitted to a general critical care setting were assessed for inclusion. Results. Four studies were selected for data extraction. A total of 44087 patients were identified with AF, of which 17.8-49.4% received anticoagulation. The reported incidence of thromboembolic events was 0-1.4% for anticoagulated patients, and 0-1.3% in non-anticoagulated patients. Major bleeding events were reported in three studies and occurred in 7.2-8.6% of the anticoagulated patients and up to 7.1% of the non-anticoagulated patients. Conclusions. There was an increased incidence of major bleeding events in anticoagulated patients with AF in critical care compared to non-anticoagulated patients. There was no significant difference in the incidence of reported thromboembolic events within studies, between patients who did and did not receive anticoagulation. However, the outcomes reported within studies were not standardised, therefore, the generalisability of our results to the general critical care population remains unclear. Further data is required to facilitate an evidence-based assessment of the risks and benefits of anticoagulation for critically ill patients with AF.

Abstract 17152: Frequency and Management of Major Bleeding in Atrial Fibrillation Patients Treated With Warfarin and Non-vitamin K Oral Anticoagulants in Community Practice: Results From the ORBIT-AF II Registry

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Benjamin A Steinberg ◽  
DaJuanicia N Simon ◽  
Laine Thomas ◽  
Jack Ansell ◽  
Gregg C Fonarow ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Vitamin K ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Recurrent Bleeding ◽  
Bleeding Events ◽  
Reversal Agents ◽  
Major Bleeding Events

Background: Non-vitamin K oral anticoagulants (NOACs) are effective at preventing stroke in patients with atrial fibrillation (AF). However, little is known about the frequency of major bleeds on NOACs and how these events are managed in clinical practice. Methods: We assessed the rates, management, and outcomes of ISTH major bleeding events among AF patients in the ORBIT-AF II registry (mean follow-up 213 days). Results: Overall, 103 patients experienced 110 major bleeding events during follow-up n=90/4986 (1.8%) on NOAC, and n=20/1320 (1.5%) on warfarin. Patients with bleeding events on NOAC were slightly younger than those on warfarin (median age 76 vs. 80; p=0.2). Among mutually-exclusive bleeding types, intracranial bleeding was more common in warfarin treated patients than NOAC-treated (15% vs 6.7%), whereas GI bleeding was more common on NOACs (56% vs. 40%, overall p=0.1 for bleeding type). Management of bleeding differed by anticoagulation type: blood products and reversal agents were more commonly used in patients on warfarin (Table). No patient received prothrombin complexes, recombinant factor VIIa, aminocaproic acid, tranexamic acid, aprotinin, or desmopressin. Out of 90 major bleeding events in NOAC patients, only 1 was fatal (1%). Within 30 days following bleeding, there were no strokes and 1 TIA (NOAC). Following a major bleed, the recurrent bleeding rate in NOAC patients in the next 30-days was 4% and the death rate was 4%. Conclusions: Rates of major bleeding with NOACs in clinical practice are comparable to those reported in clinical trials. Compared with warfarin, bleeding among NOAC users was less likely intracranial and more likely to be GI. Management of bleeding in the setting of NOAC rarely includes reversal agents.

Societal costs of venous thromboembolism and subsequent major bleeding events: a national register-based study

2019 ◽  
Vol 6 (2) ◽  
pp. 130-137
Author(s):  
Nina Gustafsson ◽  
Peter Bo Poulsen ◽  
Sandra Elkjær Stallknecht ◽  
Lars Dybro ◽  
Søren Paaske Johnsen
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Home Care Services ◽  
Care Hospital ◽  
Bleeding Events ◽  
Societal Costs ◽  
Vein Thrombosis ◽  
Primary Care Hospital ◽  
Major Bleeding Events ◽  
The Impact

Abstract Aims Detailed evidence on the societal costs of venous thromboembolism (VTE), i.e. deep vein thrombosis (DVT) and pulmonary embolism (PE), and of subsequent major bleeding events, e.g. intracranial and gastrointestinal bleedings, is limited. The objective was to estimate the average 3-year societal event costs attributable to VTE and subsequent major bleedings in Denmark. Methods and results Based on nationwide Danish registers, each incident patient diagnosed with VTE in the period from 2004 to 2016 was identified and matched with four non-VTE patients by nearest-neighbour propensity score matching. For bleeding patients, the reference cohort was VTE patients without bleedings. Event costs in terms of VTE, DVT, PE, and major bleedings in VTE patients were measured by the ‘difference-in-actual-cost’ method within 3 years after the incidence. Societal costs included healthcare costs (primary care, hospital, and prescription medicine), municipality home care services, and production loss. The study population included 74 137 VTE incident patients (DVT: 43 099; PE: 31 038), and 4887 VTE patients with a major bleeding within 3 years from VTE diagnosis. The 3-year attributable societal VTE event costs were 40 024 EUR (DVT: 34 509 EUR; PE: 50 083 EUR) with 53% of these costs appearing in the first incident year. Similar results for major bleedings were 51 168 EUR with 46% of these costs appearing in the first incident year. Conclusion The societal costs of VTE and subsequent major bleedings are substantial and ought to be considered. Estimated costs of events may be informative in evaluating the impact of preventive interventions targeting VTE and subsequent major bleedings.

P4742Evaluation of the HAS-BLED, ATRIA and ORBIT bleeding risk scores in newly diagnosed non-valvular atrial fibrillation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Bergamaschi ◽  
A Stefanizzi ◽  
M Coriano ◽  
P Paolisso ◽  
I Magnani ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Independent Predictor ◽  
Bleeding Risk ◽  
Risk Scores ◽  
Newly Diagnosed ◽  
Bleeding Events ◽  
Hemorrhagic Events ◽  
Major Bleeding Events

Abstract Background Several risk scores have been proposed to assess the bleeding risk in patients with Atrial Fibrillation. Purpose To compare the efficacy of HAS-BLED, ATRIA and ORBIT scores to predict major bleedings in newly diagnosed non-valvular AF (NV-AF) treated with vitamin K antagonists (VKAs) or new oral anticoagulants (NOACs). Methods We analyzed all consecutive patients with AF at our outpatient clinic from January to December 2017. Only those with new diagnosed NV-AF starting new anticoagulant therapy were enrolled. Major hemorrhagic events were defined according to the ISTH definition in non-surgical patients. Results Out of the 820 patients admitted with AF, 305 were newly diagnosed with NV-AF starting oral anticoagulation. Overall, 51.3% were male with a mean age of 72.6±13.7 years. Thirty-six patients (11.8%) started VKAs whereas 269 (88.2%) patients were treated with NOACs. The median follow-up time was 10.4±3.4 months. During follow-up, 123 (32.2%) bleeding events were recorded, 21 (17,1%) in the VKA group and 102 (82,9%) in the NOAC group. Eleven (2.9%) major bleeding events occurred: 5 (45.5%) in the VKA group and 6 (54.5%) in the NOAC group. Overall, patients with major hemorrhagic events showed a mean value of the scores significantly higher when compared to patients without such bleeding complications (HASBLED 3.4 vs 2.4 p=0.007; ATRIA 5.6 vs 2.4 p<0.001; ORBIT 3.6 vs 1.8 p<0,001). Conversely, when analyzing the VKA subgroup, only the ATRIA score was significantly higher in patients with major adverse events (7.4 vs 3.5 p<0.001; HAS-BLED: 4.4 vs 3.6 p=0.27; ORBIT 4.4 vs 2.9 p=0.13). An ATRIA score ≥4 identified patients at high risk of bleeding (29.4% vs. 0% events. respectively, p=0.04). In the NOAC group, patients with major bleeding events had higher mean values of ATRIA (4.0 vs 2.3 p=0.02) and ORBIT (2.8 vs 1.6 p=0,04) but not the HAS-BLED (2.5 vs 2.3 p=0.57) scores. Similarly, patients on NOACs with an ATRIA score ≥4 had higher rates of major bleedings (8.1% vs. 1.6% p=0,02). Comparing the single elements of the ATRIA score, only glomerular filtration rate <30 ml/min/1.73 mq was associated with major bleedings in the VKA group (p<0.001) whereas, in the NOAC group, anemia was strongly associated with bleeding events (p=0,02). In fact, multivariate analysis in the NOAC group showed that hemoglobin level at admission was an independent predictor for major bleeding events (OR 0.41, 95% CI 0.23–0.75, P=0.003). Conversely, in the VKA group, baseline creatinine level was an independent predictor for these events (OR 12.76, 95% CI 1.6–101.7, P=0.016). Conclusions The ATRIA score showed the best efficacy in predicting major bleeding events. Hemoglobin and creatinine levels at admission were independent predictors for major hemorrhagic events in the NOAC and in the VKA groups, respectively. The latter finding might be helpful in stratifying the hemorrhagic risk at the beginning of treatment.

Major Bleeding with Ibrutinib: More Than Expected

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3229-3229 ◽  
Author(s):  
Paul R Kunk ◽  
Joesph Mock ◽  
Michael E. Devitt ◽  
Surabhi Palkimas ◽  
Jeremy Sen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Major Bleeding ◽  
Research Funding ◽  
Bleeding Event ◽  
Lymphocytic Leukemia ◽  
Significant Activity ◽  
University Of Virginia ◽  
Bleeding Events ◽  
Major Bleeding Events

Abstract Introduction: Ibrutinib is a Bruton's tyrosine kinase inhibitor that has significant activity in treating lymphoma. While approved for patients with Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL), its activity in other lymphomas and solid tumors is under investigation and its use is increasing dramatically. Overall it is well tolerated compared to chemotherapy, but bleeding has emerged as a common adverse event with rates as high as 50% and major bleeding around 3% (Jones, abstract #1990, 2014 ASH Annual Meeting). As the use of ibrutinib increases outside of a clinical trial setting, the rate of major bleeding is likely to rise. Methods: To better understand the risk of bleeding in ibrutinib treated patients, we reviewed all patients at the University of Virginia and satellite clinics who were treated with ibrutinib between January 2012 and May 2016. Patients were required to be treated for at least 1 month with documented follow up for assessment of adverse events. Medical charts were reviewed for age, gender, ibrutinib indication and dose, length of treatment, concurrent medications, blood tests and bleeding events. All forms of anti-platelets and anticoagulants drugs, as well as medications interacting with cytochrome P450 3A4 (3A4), which metabolizes ibrutinib, were recorded. All bleeding events were recorded and graded according the Common Toxicity Criteria for Adverse Events, v4.0. Major bleeding events were reviewed by all investigators. Results: Eighty-nine patients were identified. Eighteen patients were excluded for insufficient follow up leaving 71 patients for analysis. Median age was 73 years old (44-92) with 74% male. The most common indications for treatment were CLL (65%) and MCL (27%). Most patients were treated with either 420mg (64%) or 560mg (21%). Median length of time on ibrutinib was 412 days, most with ongoing use at time of data collection. Seventy percent of patients were also treated with an anti-platelet medication, mostly aspirin for CAD with several patients on multiple anti-platelet medications. Seventeen percent were treated with an anti-coagulant, mostly apixaban for atrial fibrillation. Thirteen percent of patients (9/71) were treated with combined anti-platelet and anti-coagulant medications. Ten percent of patients were treated with a medication that has a moderate or strong interaction with 3A4. Bleeding of any grade occurred in 56% of patients, mostly bruising and epistaxis. Major bleeding, defined as grade 3 or higher, occurred in 18% of patients. Three patients developed major bleeding after an invasive procedure without ibrutinib being held. One patient died as a result of peri-procedural bleeding. Of the 9 patients treated with combined anti-platelet and anti-coagulant therapy, 78% suffered a major bleeding event. Of the ten patients on ibrutinib alone, without concurrent use of an anti-platelet, anti-coagulant or 3A4 drug interaction, no major bleeding events occurred. Conclusion: In this study examining real world use of ibrutinib, the rates of major bleeding are higher than previously reported. Most patients who suffered major bleeding were also treated with an anti-coagulant and/or anti-platelet medication. As the use of ibrutinib increases outside of clinical trials, a careful review of medications should be performed in addition to adherence to perioperative drug withholding guidelines. Patients requiring anti-coagulant and/or anti-platelet medications while on ibrutinib need careful consideration of the risks and benefits given the higher incidence of bleeding in this population. Table 1 Table 1. Disclosures Portell: AbbVie: Research Funding; Roche/Genentech: Research Funding; Infinity: Research Funding; Acerta: Research Funding. Williams:Janssen and Pharmacyclics: Research Funding; University of Virginia: Employment.

scholarly journals Efficacy and Safety of Direct Oral Factor Xa Inhibitors in Patients after Bariatric Surgery

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2439-2439 ◽  
Author(s):  
Margarita Kushnir ◽  
Radhika Gali ◽  
Mariam Alexander ◽  
Henny Heisler H. Billett
Keyword(s):  
Bariatric Surgery ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Significant Difference ◽  
Recurrent Vte ◽  
Post Bariatric Surgery

Background: Over 200,000 people underwent weight loss surgery in the United States in 2017. The absorption of numerous drugs has been shown to be altered in patients after bariatric procedures, as gastrointestinal absorptive surface, food volume, and gastric pH all affect bioavailability. Dosing of warfarin, which is commonly used for the treatment of venous thromboembolism (VTE), often needs to be adjusted, based on INR, after bariatric surgery. Since direct oral anticoagulants (DOACs), which are rapidly replacing warfarin as standard anticoagulant therapy, are not monitored, there is concern regarding their efficacy and safety in patients who have had bariatric surgery, particularly rivaroxaban, which is absorbed primarily in the stomach and must be taken with food at therapeutic doses. One study found that 9 out of 9 apixaban patients (but only 2 of 7 rivaroxaban patients) had levels that fell within the expected range after bariatric surgery. Effects of bariatric surgery on DOACs may be further complicated by baseline obesity and subsequent weight loss of the patients. The goal of our current study is to determine whether DOACs are safe and effective in preventing recurrent VTE in patients who have undergone bariatric surgery. Methods: Using our institutional database, we identified all adult patients (age ≥18 years) with a history of bariatric surgery (gastric banding, sleeve gastrectomy, and Roux-en-Y gastric bypass) who were started on anticoagulation with apixaban or rivaroxaban for VTE, between July 1, 2013 and June 30, 2018. We performed retrospective chart review to obtain information on patient demographics, BMI and type of bariatric surgery. We documented clinical outcomes of recurrent VTE and bleeding from the first prescription date to the earliest of a thrombotic event, discontinuation of medication, death, or the end of study period, June 30, 2018. VTE events were confirmed by a review of imaging studies (compression ultrasonography, ventilation/perfusions scans, and CT scans). Bleeding events were included if they met criteria for clinically relevant non-major bleeding and/or major bleeding according to the Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Safety outcomes included major bleeding (MB) and clinically relevant non-major bleeding (CRNMB). We also compared VTE recurrence and bleeding rates between the post-bariatric surgery patients and patients with BMI >40 from our prior study. Chi- squared tests were used to assess statistical significance of the differences in recurrent VTE and bleeding rates between anticoagulant cohorts. Results: Data on 102 patients were collected: 42 patients on apixaban and 60 patients on rivaroxaban. Our population was predominantly female (82.4%) with a mean age of 48.5 years and a median BMI of 35.7 at initiation of anticoagulation. Gastric bypass was the most common bariatric procedure (51%), followed by sleeve gastrectomy (37.3%), and gastric banding (11.8%). There were no recurrent VTE events in the apixaban cohort with a median follow-up duration of 137 days. Among patients on rivaroxaban, with a median follow-up of 232 days, there was one recurrent VTE (1.7%) in a patient with a BMI of 54 at the time of event. When we compared VTE recurrence rates of our combined DOAC cohort (apixaban + rivaroxaban) between our general morbidly obese population, from a prior study at our institution, and post-bariatric surgery patients, there was no statistically significant difference (2.0% vs. 1.0%, respectively, p=0.5). In bariatric surgery patients, one CRNMB event was recorded in apixaban group (2.4%) while 4 major bleeding events occurred on rivaroxaban (6.7%), p=0.3. There was no significant difference in the rate of composite MB and CRNMB between the general obesity and bariatric surgery patients (8.0% vs. 4.9%, respectively, p=0.3). Conclusions: In a review of post-bariatric surgery patients on anticoagulation for VTE, we found low rates of recurrent VTE for patients on DOACs. Although we had a relatively small sample size, the incidence of VTE recurrence was not higher in this cohort than was found in our previously published study of general obesity population. Prospective studies are needed to further investigate the efficacy and safety of direct oral anticoagulants in patients after bariatric surgery. Table. Disclosures Kushnir: Janssen Pharmaceuticals: Research Funding. Billett:Janssen: Research Funding.

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