Clinical course of pulmonary embolism patients treated with DOACs: comparing prognosis, recurrent thromboembolism, and major bleeding between patients with and without cancer

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Nakano ◽  
R Imai ◽  
M Yoshida ◽  
S Shimokata ◽  
S Adachi ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Major Bleeding ◽  
Cumulative Incidence ◽  
Clinical Course ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Patients With Cancer ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Recurrent Vte

Abstract Background Venous thromboembolism (VTE) is the third frequent acute cardiovascular syndrome in the Europe and Japan. Since direct oral anticoagulants (DOACs) are widely used now, the morbidity and mortality of pulmonary embolism (PE) patients especially associated with cancer needs to be re-evaluated. Purpose We evaluated the clinical course of patients with PE mainly treated with DOACs. Methods This retrospective observational study was conducted in a single center. The data were collected from the medical record of consecutive patients who received inpatient treatment of PE. In this study, we have compared PE patients with cancer (cancer PE) to those without cancer (non-cancer PE) and evaluated the mortality, recurrent of VTE and major bleedings. Results In total, 140 patients were enrolled: 94 patients were cancer-related, and 46 patients were without cancer (Table). The type of the tumor in cancer PE patients were as follows: gastric 8 (9%), esophageal 5 (5%), pancreatic 12 (13%), lung 14 (15%), lymphoma 2 (2%), gynecologic 17 (18%), renal 2 (2%), bile duct 8 (9%), colon 12 (13%), and others 17 (18%). Kaplan-Meier curve showed that the cumulative all-cause mortality was significantly higher in the cancer PE group (35/94 (37%) vs. 2/46 (4%), P<0.001 (log rank), HR 10.3 [95% CI:2.5–43.3]). The cumulative incidence of recurrent VTE was significantly higher in the cancer PE group (7/94 (7%) vs. 0/46, P=0.03 (log rank)). There was no significant difference in the cumulative incidence of major bleeding between the cancer PE group and the non-cancer PE group (8/94 (9%) vs. 5/46 (11%)). Conclusions The risk of recurrent VTE was still higher in cancer PE patients compared to non-cancer PE patients, although DOACs were used. Meanwhile the incidence of major bleeding was comparable in both groups, the risk of bleeding might be acceptable with using DOACs especially in cancer PE patients. Figure 1 Funding Acknowledgement Type of funding source: None

scholarly journals Direct Oral Anticoagulants Compared to Low Molecular Weight Heparin in the Treatment of Cancer-Associated Thromboembolism: An Updated Meta-Analysis of Randomized Controlled Trails

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4962-4962
Author(s):  
Sariya Wongsaengsak ◽  
Somedeb Ball ◽  
Nuvneet Khandelwal ◽  
Alay Tikue ◽  
Arunee Motes ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Patients With Cancer ◽  
Randomized Controlled ◽  
Significant Difference ◽  
Recurrent Vte

Introduction: Cancer patients have approximately 4 times higher risk of developing venous thromboembolism (VTE) compared to the general population. High tendency of bleeding from anticoagulant use in this population makes the treatment of cancer-associated thromboembolism (CAT) very challenging. Low molecular weight heparin (LMWH) is still considered as standard treatment for CAT. Direct oral anticoagulants (DOAC) have emerged as a potential alternative for LMWH due to the ease of administration and predictable pharmacokinetics, but data on DOACs in CAT is limited. Few randomized controlled trials (RCT) published recently have compared the efficacy and safety of DOACs with LMWH in the treatment of CAT. Hence, we conducted an updated meta-analysis of RCTs to determine the relative risk of recurrent VTE and bleeding complications associated with DOACs compared to LMWH in the treatment of thromboembolism in patients with cancer, and to evaluate if the risk estimates have changed since prior report (Li et al.). Methods: We performed a systemic search using Embase, Medline, and the meeting abstracts with appropriate keywords through 06/30/19, to find all RCTs comparing a DOAC with LMWH in treatment of patients with CAT. The search strategy, study selection, data extraction and analysis were performed in accordance with the Preferred Reporting Items for Meta-Analyses (PRISMA) guidelines. We pooled the point estimates in form of risk ratios (RR) with respective 95% confidence intervals (CI), using the random effects model (Mantel-Haenszel method) of Der Simonian and Laird. Heterogeneity of effect size across studies was quantified using I2 statistic and Cochran's Q. Publication bias was assessed by the Egger's regression test. All the statistical analyses were performed with the RevMan 5.3 software. Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration, 2014. Results: Overall a total of 1,739 patients with CAT (870 in the DOAC arms and 869 in LMWH arms) from three RCTs were included in the final analysis. Characteristics of studies included in the analysis are summarized in table 1. Different DOACs (Select-D: rivaroxaban, Hokusai VTE cancer: edoxaban and ADAM VTE: apixaban) were used to compare with dalteparin in included trials. Duration of anticoagulation was 6 to 12 months in these studies. Use of DOAC was associated with a significantly lower risk of recurrent VTE in comparison with LMWH [pooled RR 0.48, 95%CI: 0.26-0.87, p = 0.02, I2 = 56%, figure 1]. In addition, there was no statistically significant increase in the risk of major bleeding in patients on the DOAC arms, as compared to those on LMWH arms [ pooled RR 1.55 ,95%CI: 0.79-3.04, p = 0.20, I2 = 29%, figure 2]. Criteria for major bleeding in the studies were defined by the International Society on Thrombosis and Hemostasis. The pooled RR for clinically relevant non major bleeding (CRNMB) was 1.80 [95%CI: 0.96-3.38, p = 0.07, I2 = 60%, figure 3], thus suggesting no significant difference in risk of CRNMB between DOAC and LMWH groups. Moderate heterogeneity was noted across trials. We found no publication bias among studies included in the analysis. Conclusion: In our meta-analysis, use of DOACs for the treatment of CAT was associated with a significantly decreased risk of recurrent VTE compared to LMWH. There was no significant difference in the incidence of major or non-major bleeding events between DOAC and LMWH groups. These study results provide additional evidence for potential use of DOAC as a safe and effective alternative to LMWH for the treatment of thromboembolism in patients with cancer. Disclosures No relevant conflicts of interest to declare.

scholarly journals Direct Oral Anticoagulants for the Treatment of Acute Venous Thromboembolism Associated with Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 120 (07) ◽  
pp. 1128-1136 ◽  
Author(s):  
Michela Giustozzi ◽  
Giancarlo Agnelli ◽  
Jorge del Toro-Cervera ◽  
Frederikus A. Klok ◽  
Rachel P. Rosovsky ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Patients With Cancer ◽  
Randomized Controlled ◽  
Recurrent Vte ◽  
Acute Venous Thromboembolism

Abstract Background International guidelines have endorsed the use of edoxaban or rivaroxaban as an alternative to low-molecular-weight heparin (LMWH) for the treatment of acute venous thromboembolism (VTE) in cancer patients. Recently, a large randomized controlled trial of apixaban versus dalteparin in patients with cancer was completed. We performed an updated meta-analysis to assess the efficacy and safety of direct oral anticoagulants (DOACs) versus LMWH in patients with cancer-associated VTE. Methods MEDLINE, EMBASE, and CENTRAL (Cochrane Controlled Trials Registry) were systematically searched up to March 30, 2020 for randomized controlled trials comparing DOACs versus LMWH for the treatment of VTE in patients with cancer. The two coprimary outcomes were recurrent VTE and major bleeding at 6 months. Data were pooled by the Mantel–Haenszel method and compared by relative risk ratios (RRs) and 95% confidence intervals (CIs). Results Four randomized controlled studies (2,894 patients) comparing apixaban, edoxaban, or rivaroxaban with dalteparin were included in the meta-analysis. Recurrent VTE occurred in 75 of 1,446 patients (5.2%) treated with oral factor Xa inhibitors and in 119 of 1,448 patients (8.2%) treated with LMWH (RR 0.62; 95% CI 0.43–0.91; I 2, 30%). Major bleeding occurred in 62 (4.3%) and 48 (3.3%) patients receiving oral factor Xa inhibitors or LMWH, respectively (RR 1.31; 95% CI 0.83–2.08; I 2, 23%). Conclusion In patients with cancer-associated VTE, oral factor Xa inhibitors reduced the risk of recurrent VTE without a significantly higher likelihood of major bleeding at 6 months compared with LMWH.

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.

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

Blood ◽  
2020 ◽  
Vol 136 (12) ◽  
pp. 1433-1441 ◽  
Author(s):  
Frits I. Mulder ◽  
Floris T. M. Bosch ◽  
Annie M. Young ◽  
Andrea Marshall ◽  
Robert D. McBane ◽  
...  
Keyword(s):  
Systematic Review ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Patients With Cancer ◽  
Recurrent Vte

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

scholarly journals Renal function and clinical outcome of patients with cancer-associated venous thromboembolism randomized to receive apixaban or dalteparin. Results from the Caravaggio trial.

Haematologica ◽  
2020 ◽  
pp. 0-0
Author(s):  
Cecilia Becattini ◽  
Rupert Bauersachs ◽  
Giorgio Maraziti ◽  
Laurent Bertoletti ◽  
Alexander Cohen ◽  
...  
Keyword(s):  
Renal Function ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Metastatic Cancer ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Patients With Cancer ◽  
Relative Safety ◽  
Recurrent Vte

The effect of renal impairment (RI) on risk of bleeding and recurrent thrombosis in cancer patients treated with direct oral anticoagulants for venous thromboembolism (VTE) is undefined. We run a prespecified analysis of the randomized Caravaggio study to evaluate the role of RI as risk factor for bleeding or recurrence in patients treated with dalteparin or apixaban for cancer-associated VTE. RI was graded as moderate (creatinine clearance between 30-59 ml/minute; 275 patients) and mild (between 60-89 ml/minute; 444 patients). In 1142 patients included in this analysis, the incidence of major bleeding was similar in patients with moderate vs. no or mild RI (HR 1.06, 95% CI 0.53-2.11), with no difference in the relative safety of apixaban and dalteparin. Recurrent VTE was not different in moderate vs. no or mild RI (HR 0 .67, 95% CI 0.38-1.20); in moderate RI, apixaban reduced recurrent VTE compared to dalteparin (HR 0.27, 95% CI 0.08-0.96; P for interaction 0.1085). At multivariate analysis, no association was found between variation of renal function over time and major bleeding or recurrent VTE. Advanced or metastatic cancer was the only independent predictor of major bleeding (HR 2.84, 95% CI 1.20-6.71), with no effect of treatment with apixaban or dalteparin. In our study in cancer patients treated with apixaban or dalteparin, moderate RI was not associated with major bleeding or recurrent VTE. In patients with moderate renal failure, the safety profile of apixaban was confirmed with the potential for improved efficacy in comparison to dalteparin.

scholarly journals Safety and efficacy of direct oral anticoagulants (DOACs) vs low molecular weight heparin (LMWH) in malignancy induced venous thromboembolism-a systematic review and meta analysis

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
A Abdul Razzack ◽  
N Hussain ◽  
S Adeel Hassan ◽  
S Mandava ◽  
F Yasmin ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Efficacy And Safety ◽  
Dichotomous Data ◽  
Significant Difference

Abstract Funding Acknowledgements Type of funding sources: None. Background- Low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs) have been proven to be more effective in the management of venous thromboembolism (MVTE). The efficacy and safety of LMWH or DOACs in treatment of recurrent or malignancy induced VTE is not studied in literature. Objective To compare the efficacy and safety of LMWH and  DOACs in the management of malignancy induced  VTE Methods- Electronic databases ( PubMed, Embase, Scopus, Cochrane) were searched from inception to November  28th, 2020. Dichotomous data was extracted for prevention of VTE and risk of major bleeding in patients taking either LMWH or DOACs. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p < 0.05.  Results- Three studies with 2607 patients (DOACs n = 1301 ; LMWH n = 1306) were included in analysis. All the study population had active cancer of any kind diagnosed within the past 6 months. Average follow-up period for each trial was 6 months. Patients receiving DOACs have a lower odds of recurrence of MVTE as compared to LMWH( OR 1.56; 95% CI 1.17-2.09; P = 0.003, I2 = 0). There was no significant difference in major bleeding among patients receiving LMWH or DOACs  (OR-0.71, 95%CI 0.46-1.10, P = 0.13, I2 = 22%) (Figure 1). We had no publication bias in our results (Egger’s regression p > 0.05). Conclusion- DOACs are superior to LMWH in prevention of MVTE and have similar major bleeding risk as that of LMWH. Abstract Figure. A)VTE Recurrence B)Major Bleeding events

Abstract 12901: Novel Oral Anticoagulants Are Associated With Decreased Recurrence of Venous Thromboembolism in Patients With Cancer: An Updated Meta-Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sunil Upadhaya ◽  
Seetharamprasad Madala ◽  
Sunil Badami
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Novel Oral Anticoagulants ◽  
P Value ◽  
Patients With Cancer ◽  
Randomized Controlled ◽  
All Cause Mortality ◽  
Recurrent Vte

Introduction: Patients with cancer are at high risk for recurrent thromboembolic phenomenon. Use of novel oral anticoagulants (NOAC) for treatment of venous thromboembolism (VTE) in such patients is controversial. We conducted this updated meta-analysis to evaluate the pooled efficacy and safety of NOAC in patients with cancer. Methods: We did systematic search of PubMed and Cochrane library databases for randomized controlled trials comparing NOAC with low molecular weight heparin (LMWH) for VTE treatment in cancer patients till April 2020. The efficacy outcomes were recurrent VTE and all-cause mortality rates, and the primary safety outcome was incidence of major bleeding rate. Results: Four randomized controlled studies comparing NOAC with LMWH (1446 patients in NOAC group and 1448 patients in LMWH group) were included in our study. Use of NOAC lead to significant reduction in recurrent VTE rate (odds ratio (OR): 0.55 [0.36-0.84], I 2 = 45 %, p value = 0.006) (Figure 1). However, we did not find any significant difference in rate of major bleeding (OR: 1.30 [0.76-2.23], I 2 = 35%, p value = 0.34) (Figure 2) and all-cause mortality (OR: 1 [0.80 - 1.26], I 2 = 33%, p value = 0.98). Conclusions: This updated meta-analysis showed comparatively lower pooled recurrent VTE rate in patient being treated with NOAC, whereas similar rates of major bleeding and all-cause death. NOAC are more efficacious and has similar safety profile compared with LMWH.

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<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<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<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.

P690Incidence of events between vitamin K antagonists and direct oral anticoagulants in patients with cancer

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Pardo Sanz ◽  
L M Rincon ◽  
G De Lara ◽  
A Tamayo ◽  
L C Belarte ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin K ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Risk ◽  
Systemic Embolism ◽  
Bleeding Events ◽  
Patients With Cancer

Abstract Background Balance between embolic and bleeding risk is challenging in patients with cancer. There is a lack of specific recommendations for the use of antithrombotic therapy in oncologic patients with atrial fibrillation (AF). We aimed to evaluate the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) within patients with breast cancer. We also compared the embolic and bleeding risk, the preventive management and the incidence of events between patients with and without cancer. Methods It is an ambispective observational multicentric study that analysed patients with non-valvular AF treated in Oncology and Cardiology Departments in Spain in the period 2011–2018. A total of 1237 female patients with AF were enrolled: 637 with breast cancer and 599 without cancer. The incidence of thromboembolic and major bleeding events according to the antithrombotic strategy with VKAs or DOACs was evaluated in the cohort of 637 patients with cancer. Analysis were conducted using SPSS software V.22.0 and R V.3.5.1, with a two-tailed significance value of 0.05. Results Mean follow-up was 3.1 years. Both groups were similar in age, CHA2DS2-VASc and HASB-LED scores. There was no evidence that the incidence of ischemic stroke/systemic embolism differed between patients with cancer treated with AVK and DOAC after CHA2DS2-VASc adjustment: HR 0.91 (95% CI, 0.42–1.99). In addition, no significant differences in the incidence of major bleeding events were found between DOACs and VKA after adjustment for HAS-BLED score: HR 1.53 (95% CI, 0.93–2.53) (Figure 3). Gastrointestinal bleeding was the main source of haemorrhages in both groups (45% of bleedings among patients treated with DOACs and, 37% in VKAs group). Metastatic disease or active chemotherapy were studied as potential covariates but none of them posed any relevant change in the result. Kaplan-Meier analysis Conclusions Cancer patients treated with DOACs did not differ versus those treated with VKAs with regards to stroke or systemic embolism in a model adjusted for CHA2DS2-VASc. Neither significant differences were found for bleeding events in a model adjusted for baseline HASBLED.

Direct oral factor Xa inhibitors for the treatment of acute cancer-associated venous thromboembolism: A systematic review and network meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23156-e23156
Author(s):  
Harry E Fuentes ◽  
Robert McBane ◽  
Waldemar Wysokinski ◽  
Alfonso Javier Tafur ◽  
Charles L. Loprinzi ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Indirect Comparison ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Efficacy And Safety ◽  
Patients With Cancer

e23156 Background: A direct meta-analysis was performed to explore the efficacy and safety of direct oral factor Xa inhibitors with dalteparin in patients with cancer associated acute venous thromboembolism (VTE). Also, the comparative efficacy and safety of apixaban, rivaroxaban, and edoxaban was assessed with a network meta-analysis. Methods: MEDLINE, CENTRAL, and EMBASE were searched for trials comparing direct oral anticoagulants (DOACs) to dalteparin for the management of cancer associated acute VTE. A network meta-analysis using both frequentist and Bayesian methods was performed to analyze VTE recurrence, major and clinically relevant non-major bleeding (CRNMB). Results: Three randomized control trials, at low risk of bias, enrolled 1,739 patients with cancer associated VTE. Direct comparison showed a lower rate of VTE recurrence in DOAC compared to dalteparin groups (odds Ratio [OR]:0.48, 95% Confidence interval [CI]:0.24-0.96; I2:46%). Indirect comparison suggested that apixaban had greater reduction in VTE recurrence compared to dalteparin (OR: 0.10; 95% CI: 0.01–0.82), but not rivaroxaban or edoxaban. Apixaban also had the highest probability of being ranked most effective. By direct comparisons, there was an increased likelihood of major bleeding in the DOAC group compared to dalteparin (OR: 1.70; 95% CI: 1.04–2.78). CRNMB did not differ. Indirect estimates were imprecise. Subgroup analyses in gastrointestinal cancers suggested that dalteparin may have the lowest risk of bleeding whereas estimates in urothelial cancer were imprecise. Conclusions: DOACs appear to lower the risk of VTE recurrence compared to daltaparin while increasing major bleeding. Apixaban may be associated with the lowest risk of VTE recurrence compared to the other DOACs.

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