Efficacy and Safety of Andexanet Alfa for Bleeding Caused by Factor Xa Inhibitors: A Systematic Review and Meta-Analysis

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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Low-dose of oral factor Xa inhibitors in patients with a recent acute coronary syndrome: A systematic review and meta-analysis of randomized trials

Atherosclerosis ◽

10.1016/j.atherosclerosis.2013.04.022 ◽

2013 ◽

Vol 229 (2) ◽

pp. 482-488 ◽

Cited By ~ 4

Author(s):

Karolina Obonska ◽

Eliano Pio Navarese ◽

Alexandra Lansky ◽

Giuseppe Tarantini ◽

Roberta Rossini ◽

...

Keyword(s):

Systematic Review ◽

Acute Coronary Syndrome ◽

Randomized Trials ◽

Low Dose ◽

Meta Analysis ◽

Factor Xa ◽

Factor Xa Inhibitors ◽

Coronary Syndrome

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Direct oral factor Xa inhibitors for the prevention of non-central nervous systemic embolism patients with non-valvular atrial fibrillation - a systematic review and meta-analysis

VASA ◽

10.1024/0301-1526/a000540 ◽

2016 ◽

Vol 45 (4) ◽

pp. 293-298

Author(s):

Victoria Gandara ◽

Fernando Vazquez ◽

Esteban Gandara

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Ischaemic Stroke ◽

Vitamin K ◽

Meta Analysis ◽

Factor Xa ◽

Factor Xa Inhibitors ◽

Secondary Outcome ◽

Controlled Trials ◽

Systemic Embolism

Abstract. Background: The aim of this systematic review and meta-analysis was to evaluate the efficacy of direct oral factor Xa inhibitors for preventing non-central nervous systemic embolism in patients with non-valvular atrial fibrillation. Methods: We conducted a systematic review of the following databases: Ovid Medline, Europubmed, Embase, and the Cochrane Central Register of Controlled Trials, from July 1st 1990 to April 1st, 2015. Randomised controlled trials were included if they reported the outcomes of patients with non-valvular atrial fibrillation treated with a direct oral factor Xa inhibitors compared to a vitamin K antagonist. The primary outcome was objectively confirmed as non-central nervous systemic embolism and ischaemic stroke was the secondary outcome. The random-effects model odds ratio was used as the outcome measure. Results: Our initial search identified 987 relevant articles, of which three satisfied our inclusion criteria and were included. Compared to vitamin K antagonists targeting an INR between 2 and 3, direct oral factor Xa inhibitors alone did not reduce the incidence of non-central nervous systemic embolism [OR 0.63 (95 % CI 0.30 - 1.35)] or ischaemic stroke [OR 1.06 (95 % CI 0.86 - 1.32)]. Conclusions: As a drug class, direct oral factor Xa inhibitors do not reduce the incidence of non-central nervous systemic embolism (or ischaemic stroke) in patients with non-valvular atrial fibrillation. Selecting drugs for the prevention of non-central nervous systemic embolism in patients with non-valvular atrial fibrillation should be based on individual drug efficacy data, rather than class data.

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Comparison between direct factor Xa inhibitors and low-molecular-weight heparin for efficacy and safety in the treatment of cancer-associated venous thromboembolism: A meta-analysis

Journal of Cancer Research and Therapeutics ◽

10.4103/jcrt.jcrt_68_19 ◽

2019 ◽

Vol 15 (7) ◽

pp. 1541 ◽

Cited By ~ 2

Author(s):

Min Yang ◽

Jiang Li ◽

Rui Sun ◽

Yanfeng Wang ◽

Haiyan Xu ◽

...

Keyword(s):

Molecular Weight ◽

Venous Thromboembolism ◽

Low Molecular Weight Heparin ◽

Meta Analysis ◽

Factor Xa ◽

Factor Xa Inhibitors ◽

Low Molecular Weight ◽

Efficacy And Safety ◽

Direct Factor ◽

Direct Factor Xa Inhibitors

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Factor Xa inhibitor for venous thromboembolism management in patient with cancer: a systematic review and meta-analysis

F1000Research ◽

10.12688/f1000research.73883.1 ◽

2021 ◽

Vol 10 ◽

pp. 1257

Author(s):

Johanes Nugroho Eko Putranto ◽

Ardyan Wardhana ◽

Yoga Alfian Noor ◽

Pirhot Lambok Marnala Yosua Siahaan ◽

Makhyan Jibril Al Farabi

Keyword(s):

Systematic Review ◽

Venous Thromboembolism ◽

Major Bleeding ◽

Fixed Effects ◽

Meta Analysis ◽

Factor Xa ◽

Factor Xa Inhibitors ◽

Cochrane Library ◽

Factor Xa Inhibitor ◽

Patients With Cancer

Background: An earlier systematic review reported no differences in the incidence of recurrent venous thromboembolism and major bleeding between factor Xa inhibitors and standard anticoagulation. The present meta-analysis aimed to assess the effectiveness of factor Xa inhibitors for the management of venous thromboembolism (VTE), specifically in patients with cancer, as there were more randomized clinical trials (RCTs) available. Methods: The PubMed and Cochrane Library databases were systematically screened for all RCTs assessing factor Xa inhibitor efficacy for VTE management in cancer patients. Using RevMan 5.3, we performed a Mantel–Haenszel fixed-effects meta-analysis of the following outcomes: recurrent VTE, VTE events, and major bleeding rates. Results: We identified 11 studies involving 7,965 patients. Factor Xa inhibitors were superior in preventing VTE recurrence, compared to low-molecular-weight heparin (LMWH) (OR 0.60; 95% CI 0.45–0.80; P < 0.01) and vitamin K antagonists (VKA) (OR 0.51; 95% CI 0.33–0.78; P < 0.01). As prophylaxis, factor Xa inhibitors had a similar rate of VTE compared to VKAs (OR 1.08 [95% CI 0.31–3.77]; P = 0.90) and a lower rate compared to placebo (OR 0.54 [95% CI 0.35–0.81]; P < 0.01). Major bleeding rates were higher with factor Xa inhibitors than with LMWHs (OR 1.34 [95% CI 0.83–2.18]; P = 0.23), but significantly lower than VKAs (OR 0.71 [95% CI 0.55–0.92]; P < 0.01). Conclusions: Factor Xa inhibitors are effective for VTE management in patients with cancer; however, they are also associated with an increased bleeding risk compared to LMWH, but decreased when compared to VKA.

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Extended treatment of venous thromboembolism: a systematic review and network meta-analysis

Heart ◽

10.1136/heartjnl-2018-313617 ◽

2018 ◽

Vol 105 (7) ◽

pp. 545-552 ◽

Cited By ~ 6

Author(s):

Kang-Ling Wang ◽

Nick van Es ◽

Chris Cameron ◽

Lana A Castellucci ◽

Harry R Büller ◽

...

Keyword(s):

Venous Thromboembolism ◽

Major Bleeding ◽

Low Dose ◽

Meta Analysis ◽

Factor Xa ◽

Factor Xa Inhibitors ◽

Efficacy And Safety ◽

Standard Intensity ◽

All Cause Mortality ◽

Dose Factor

ObjectiveTo evaluate efficacy and safety of oral anticoagulant regimens and aspirin for extended venous thromboembolism (VTE) treatment.MethodsWe searched MEDLINE, Embase, CENTRAL and conference proceedings for randomised controlled trials studying vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or aspirin for secondary prevention of VTE beyond 3 months. ORs (95% credible intervals) between treatments were estimated using random-effects Bayesian network meta-analysis.ResultsSixteen studies, totaling more than 22 000 patients, were included. Compared with placebo or observation and with aspirin, respectively, the risk of recurrent VTE was lower with standard-intensity VKAs (0.15 (0.08 to 0.24) and 0.23 (0.09 to 0.54)), low-dose factor Xa inhibitors (0.16 (0.06 to 0.38) and 0.25 (0.09 to 0.66)), standard-dose factor Xa inhibitors (0.17 (0.08 to 0.33) and 0.27 (0.11 to 0.65)) and the direct thrombin inhibitor (0.15 (0.04 to 0.37) and 0.23 (0.06 to 0.74)) although the risk of major bleeding was higher with standard-intensity VKAs (4.42 (1.99 to 12.24) and 4.14 (1.17 to 18.86)). Effect estimates were consistent in male patients and those with index pulmonary embolism or with unprovoked VTE and in sensitivity analyses. In addition, compared with placebo or observation, the risk of all-cause mortality was reduced with standard-intensity VKAs (0.44 (0.20 to 0.87)) and low-dose factor Xa inhibitors (0.38 (0.12 to 0.995)).ConclusionsStandard-intensity VKAs and DOACs are more efficacious than aspirin for extended VTE treatment. Despite a higher risk of major bleeding, standard-intensity VKAs was associated with a lower risk of all-cause mortality. Since overall efficacy and safety of standard-intensity VKAs and DOACs are in equipoise, patient factors, costs and patient preferences should be considered when recommending extending anticoagulation treatment.

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