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.

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

TH Open ◽  
2020 ◽  
Vol 04 (03) ◽  
pp. e145-e152 ◽  
Author(s):  
Yimin Pearl Wang ◽  
Rohan Kehar ◽  
Alla Iansavitchene ◽  
Alejandro Lazo-Langner
Keyword(s):  
Lower Risk ◽  
Observational Studies ◽  
Randomized Trials ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Funding Source ◽  
Risk Of Bleeding ◽  
Study Type

Abstract Introduction In randomized trials in atrial fibrillation (AF) patients on direct oral anticoagulants (DOACs) have a lower risk of bleeding compared with warfarin. However, data from randomized trials may not extrapolate to general population. We aimed to determine the risk of bleeding in patients on DOACs in observational studies. Materials and Methods Observational studies from 1990 to January 2019 were included. A pooled effect hazard ratio (HR) was calculated with a random effects model using the generic inverse variance method. Subgroup analyses according to previous anticoagulants exposure, study type, funding source, and DOAC type (direct thrombin inhibitors vs. factor Xa inhibitors) were conducted. Results A total of 35 studies comprising 2,356,201 patients were included. The average pooled HR for observational data was 0.78 (95% confidence interval [CI] 0.71, 0.85). There were no statistically significant differences in pooled HR by previous exposure to anticoagulants, DOAC type (direct thrombin vs. factor Xa inhibitors), study type, and funding source. Among patients receiving factor Xa inhibitors, patients on apixaban had a lower risk of bleeding compared with warfarin (HR 0.60, 95% CI 0.50, 0.71, p < 0.001) in contrast to those on rivaroxaban (HR 0.98, 95% CI 0.91, 1.06, p = 0.60). Conclusion In observational studies, AF patients on DOACs experience less bleeding events compared with warfarin; however, apixaban and dabigatran, but not rivaroxaban, have a lower risk of bleeding than warfarin.

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.

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.

scholarly journals Safety of Direct Oral Anticoagulants in Patients with Cirrhosis: A Systematic Review and Meta-Analysis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1238-1238
Author(s):  
Kamolyut Lapumnuaypol ◽  
Thita Chiasakul
Keyword(s):  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Bleeding Events ◽  
Randomized Controlled ◽  
Significant Difference ◽  
Cirrhotic Patients

Abstract Introduction: The coagulopathy of cirrhosis is characterized by a complex rebalanced hemostasis which increases the risk of bleeding as well as thrombosis. For the treatment and prevention of thromboembolism, low-molecular weight heparin (LMWH) and vitamin K antagonists, such as warfarin, are generally used in cirrhotic patients. Although efficacious, these agents are inconvenient due to the parenteral route of administration, need for monitoring, and interactions with food or drugs. Direct oral anticoagulants (DOACs) may provide safe and effective alternatives for patients with cirrhosis. However, data concerning their safety profile in this population are limited given that patients with advanced liver diseases were excluded from most clinical trials. To address this, we conducted a systematic review and meta-analysis to evaluate the safety of DOACs compared to warfarin or low-molecular weight heparin (LMWH) in patients with cirrhosis. Methods: A systematic literature search was performed using MEDLINE and EMBASE from inception up to June 2018. We included prospective and retrospective studies involving adults ≥18 years with cirrhosis of any stage in whom anticoagulants were indicated for any indications. Included studies are required to report the incidence, odds ratio, or hazard ratio of bleeding events in both patients receiving DOACs and patients receiving warfarin or LMWH (controls). Two authors independently searched the literature, screened for eligibility, and extracted the data. Any discrepancies were resolved by reaching consensus. Primary outcome of interest was all-cause bleeding events. Secondary outcome was major bleeding. Data analysis was performed using Review Manager version 5.3. For all-cause bleeding, pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using Mantel-Haenszel method. For major bleeding, effect estimates and standard errors from individual studies were combined by the generic inverse variance method of DerSimonian and Laird. Random-effects model was used in all analyses. Inter-study heterogeneity was evaluated using Cochran's Q test and I2statistics. Results: A total of 279 articles were identified from MEDLINE and EMBASE, of which 93 were removed because of duplication. After screening by title and abstract, 174 articles were excluded. Full text of 12 articles were reviewed, of which 5 studies (4 observational studies and 1 randomized controlled trial) with a total of 447 patients met eligibility criteria and were included in the final analysis. The indications for anticoagulants included atrial fibrillation, deep venous thrombosis, pulmonary embolism, and portal vein thrombosis. The DOACs used in these studies included dabigatran, rivaroxaban, apixaban, and edoxaban. Heterogeneity among studies was low to moderate. Compared to controls, the use of DOACs in cirrhotic patients did not show any significant difference in all-cause bleeding (RR 0.72; 95% CI, 0.32-1.63; I2=59%, Figure 1). Among 3 studies that reported major bleeding, there was no significant difference in major bleeding between both groups (OR 0.46; 95% CI, 0.10-2.09; I2=42%, Figure 2). Conclusions: Our study demonstrates that, compared to those who were treated with traditional anticoagulants, cirrhotic patients who were treated with DOACs had no significant increase risk of all-cause bleeding and major bleeding. The use of DOACs in patents with cirrhosis appears to be as safe as traditional anticoagulants. Further randomized controlled studies involving larger numbers of patients are required to explore the efficacy as well as potential beneficial effects of DOACs for each indications in cirrhotic patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Slightly elevated international normalized ratio predicts bleeding episodes in patients treated with direct oral anticoagulants

2020 ◽  
Vol 48 (6) ◽  
pp. 030006051989443
Author(s):  
Priya Bhardwaj ◽  
Louise Breum Petersen ◽  
Tomas Sorm Binko ◽  
Jan Roland Petersen ◽  
Gitte Gleerup Fornitz
Keyword(s):  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Bleeding Risk ◽  
International Normalized Ratio ◽  
Direct Factor ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
Direct Factor Xa Inhibitors ◽  
Bleeding Episodes

Introduction Patients treated with direct oral anticoagulants (DOACs) are at increased bleeding risk. It is therefore of increasing interest to identify predictors of bleeding episodes to increase safety during treatment with DOACs. Methods This retrospective cohort study systematically reviewed medical records of 235 patients treated with either apixaban, rivaroxaban or dabigatran for non-valvular atrial fibrillation or venous thromboembolism and collected data on the international normalized ratio (INR) and all bleeding episodes. Results INR ≥ 1.5 was significantly associated with increased risk of minor and major bleeding events in patients treated with direct factor Xa inhibitors. This association was not present in patients treated with dabigatran. However, a high negative predictive value was identified for INR < 1.5 for all drugs. The relative risks of bleeding episodes in patients with INR ≥ 1.5 and INR < 1.5 were 5.1 and 0.20, respectively. Conclusions Our results demonstrate a strong correlation between INR and risk of bleeding episodes during DOAC treatment. INR < 1.5 was a strong negative predictor for low bleeding risk independent of indication or choice of drug, and INR ≥ 1.5 was associated with increased risk of bleeding episodes in patients treated with direct factor Xa-inhibitors.

Anticoagulant and Antiplatelet therapy for the prevention of stroke in AF with arterial origin stroke: a meta-analysis.

2019 ◽  
Author(s):  
Mingxia Li ◽  
Hong Lin ◽  
Jiankuan Shi ◽  
Qianru Yang ◽  
Jianjun Li ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Cochrane Library ◽  
Stroke Recurrence ◽  
Efficacy And Safety ◽  
Systemic Embolism ◽  
Risk Of Bleeding

Abstract Background Anticoagulation and antiplatelet therapy were adopted respectively for the prevention ofcardio-embolic stroke or arterial origin stroke. while it’s difficult to make decisions for individual with Atrial fibrillation(AF)and arterial origin stroke as comorbidities, so we attempted to evaluate the efficacy and safety ofanticoagulants and antiplatelet forthe prevention of stroke in AF with arterial origin stroke and make an optimal treatment for these comorbidities. Methods Databases included PubMed, Cochrane Library and ClinicalTrials.gov were searched up to 31 Aug 2019. Eight RCTs with 77048 participants were enrolled. Results Direct oral anticoagulants(DOACs) reduced the relative risk of stroke and systemic embolism by 15% (95%CI 0.75-0.97, I2=65.6%) and the major bleeding by 23%(95%CI 0.63-0.95, I2=92.3%,). DOACs or warfarin plus aspirin compared with DOACs or warfarin alone did not show the benefit on stroke and systemic embolism prevent in AF patients, but increase the risk of major bleeding with RR 1.40 (95%CI 1.13-1.75,) and 1.33（95%CI 1.09-1.63）respectively. No differences in preventionof ischemic stroke were detected between OACs versus aspirin in arterial origin stroke. The major bleeding was significantly higher in the OACs group (RR,2.40,1.46-3.94, I2=62.2%). However, compared with aspirin, rivaroxabandid not increase the risk of major bleeding in Branch atheromatous stroke (RR,1.54,95%CI 0.26-9.12). Conclusions We speculatedthat DOACs alone may be enough to prevent stroke recurrence and not to increase the risk of bleeding in AF patients with arterial origin stroke. The well designed RCTs with the direct comparison would be needed in future.

scholarly journals Real-world comparison of major bleeding risk among non-valvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban, or warfarin

2016 ◽  
Vol 116 (11) ◽  
pp. 975-986 ◽  
Author(s):  
Allison Keshishian ◽  
Shital Kamble ◽  
Xianying Pan ◽  
Jack Mardekian ◽  
Ruslan Horblyuk ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Real World ◽  
Lower Risk ◽  
Proportional Hazards ◽  
Oral Anticoagulants ◽  
Bleeding Risk ◽  
Baseline Period ◽  
Cox Proportional Hazards ◽  
Significant Difference

SummaryIn addition to warfarin, there are four non-vitamin K antagonist oral anticoagulants (NOACs) available for stroke prevention in non valvular atrial fibrillation (NVAF). There are limited data on the comparative risks of major bleeding among newly anticoagulated NVAF patients who initiate warfarin, apixaban, dabigatran, or rivaroxaban, when used in ‘real world’ clinical practice. The study used the Truven MarketScan® Commercial & Medicare supplemental US claims database. NVAF patients aged ≥18 years newly prescribed an oral anticoagulant 01JAN2013–31DEC2014, with a ≥1-year baseline period, were included (study period: 01JAN2012–31DEC2014). Major bleeding was defined as bleeding requiring hospitalisation. Propensity score matching (PSM) was used to balance age, sex, region, baseline comorbidities, and comedications. Cox proportional hazards models were used to estimate the PSM hazard ratio (HR) of major bleeding. Among 45,361 newly anticoagulated NVAF patients, 15,461 (34.1 %) initiated warfarin, 7,438 (16.4 %) initiated apixaban, 17,801 (39.2 %) initiated rivaroxaban, and 4,661 (10.3 %) initiated dabigatran. Compared to matched warfarin initiators, apixaban (HR: 0.53; 95 % CI: 0.39–0.71) and dabigatran (HR: 0.69; 95 % CI: 0.50–0.96) initiators had a significantly lower risk of major bleeding. Patients initiating rivaroxaban (HR: 0.98; 95 % CI: 0.83–1.17) had a non-significant difference in major bleeding risk compared to matched warfarin patients. When comparisons were made between NOACs, matched rivaroxaban patients had a significantly higher risk of major bleeding (HR: 1.82; 95 % CI: 1.36–2.43) compared to apixaban patients. The differences for apixaban-dabigatran and dabigatran-rivaroxaban matched cohorts were not statistically significant. Among newly anticoagulated NVAF patients in the real-world setting, apixaban and dabigatran initiation was associated with significantly lower risk of major bleeding compared to warfarin initiation. When compared to apixaban, rivaroxaban initiation was associated with significantly higher risk of major bleeding.Note: The review process for this paper was fully handled by Christian Weber, Editor in Chief.Supplementary Material to this article is available online at www.thrombosis-online.com.

scholarly journals Safety and Efficacy of Direct Oral Anticoagulants in Morbidly Obese Patients: A Meta-Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1166-1166
Author(s):  
Talha Aijaz ◽  
Okechukwu Nwabueze Obi ◽  
Nida Khokhar ◽  
Prasanth Lingamaneni ◽  
Muhammad Zain Farooq
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Observational Studies ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Efficacy And Safety ◽  
Randomized Control

Background: Direct oral anticoagulants (DOACS) were recently approved for anticoagulation in patients with atrial fibrillation for prevention of stroke and patient with venous thromboembolism (VTE) for the prevention of recurrent VTE. They have shown comparable efficacy and safety compared to vitamin K antagonist (VKA). DOACS have uniform pharmacokinetics and pharmacodynamics; hence, regular monitoring is not required. The morbidly obese patients may have increased volume of distribution and altered clearance which may alter the pharmacokinetics and consequently efficacy and safety of DOACS in these patients. 2016 International Society of Thrombosis and Hemostasis guideline recommends avoiding DOACS in a patient with body mass index (BMI) >40 kg/m2 or with body weight >120 kg due to lack of clinical trials. There is no sizeable randomized control trial to study the outcome of DOACS in morbidly obese patients, but subgroup analysis of a major randomized control trials and observational studies may provide the data on the efficacy and safety of DOACS. We intend to utilize this data in this meta-analysis to study the effectiveness and safety of DOACS in morbidly obese patients. Methods: Eligibility Criteria- Randomized control trial, observational studies including patients above 18 years with BMI>40kg/m2, body weight>120 kg and history of atrial fibrillation or VTE who are taking DOACS or warfarin for therapeutic purpose were included in the analysis. Study Selection- We searched Medline and Cochrane database. 52 studies were identified and 43 remained after removing duplicates. After assessing full text for eligibility 5 studies were included in the meta-analysis. Statistical analysis- Statistical analysis was performed with Review manager 5.3 by the Cochrane Collaboration. Forest plot was used to analyze publication bias. Heterogeneity in the studies were analyzed with Cochran Q analysis and I2 statistics. Results: Population characteristics were available in four studies. The mean age of the population ranged from 61.7 to 66.8 years, and mean BMI ranged from 44.8 to 46.7 kg/m2 . I2 analysis showed that the studies included were homogeneous, so fixed-effect model was applied. The incidence of recurrent VTE, stroke, or death ranged from 1.5% to 7.3% in DOACS compared to 1.2% to 7.9% in warfarin except in one study by Kalani et al. where it was 26% in DOACS vs. 20% in warfarin. Relative risk was 0.96 (confidence interval 0.75 - 1.28, p 0.78) indicating there was no significant difference in the primary efficacy outcome between the two groups. The incidence of major bleeding ranged from 1.5% to 4.8% in DOACS compared to 2.6% to 6.1% in warfarin. Relative risk was 0.72 (confidence interval 0.56 - 0.93, p 0.01) indicating that the risk of major bleeding was low among patient using DOACS. Conclusion: Efficacy of DOACS is similar compared to VKA when used for prevention of recurrence in VTE or prevention of stroke in atrial fibrillation in the patients with BMI>40 kg/m2 or bodyweight >120 kg. There was a trend towards a lower risk of bleeding in the patients with DOACS which is similar to the risk of major bleeding reported in non-obese patients in landmark randomized clinical trials. Only two studies included the patients with VTE, and additional studies are required to assess the safety and efficacy of DOACS among morbidly obese individuals with VTE. Figure Disclosures No relevant conflicts of interest to declare.

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.

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