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      Real-World Effectiveness and Safety of Apixaban versus Warfarin in Patients with Acute Venous Thromboembolism: Experience of a Large Tertiary Hospital in Saudi Arabia

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          Abstract

          Purpose

          The main objective of this study was to evaluate the effectiveness and safety of apixaban versus warfarin in patients with venous thromboembolism (VTE) in a “real-world” setting.

          Patients and Methods

          A retrospective cohort study was conducted using data from a large tertiary hospital in Saudi Arabia. Patients were included if they were adults (≥18 years), diagnosed with VTE, and treated with either apixaban or warfarin between January 2016 and September 2018. Patients who had received anticoagulation therapy within three months of the date of the index event were excluded. The effectiveness outcomes were incidence of VTE recurrence (ie, deep vein thrombosis DVT or pulmonary embolism [PE]), while the safety outcome was incidence of any major bleeding (MB) event within 90 days of follow-up.

          Results

          Among the 492 patients included for study, 212 (43.1%) received apixaban and 280 (56.1%) received warfarin. The mean age of patients was 53.6±19.1 years and 62% of the cohort was female. Comparable rates of VTE recurrence were observed for apixaban and warfarin treatment groups during follow-up (adjusted odds ratio (AOR) =0.95; 95% CI 0.53–1.68), including DVT (AOR=1.06; 95% CI 0.52–2.17) and PE (AOR=0.78; 95% CI 0.31–1.96). However, apixaban was associated with significantly fewer MB events than warfarin (AOR=0.18; 95% CI 0.04–0.83).

          Conclusion

          The use of apixaban for the treatment of Saudi patients with acute VTE is associated with a VTE recurrence rate comparable to that of warfarin, with significantly fewer MB events.

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          Most cited references18

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          Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients.

          Summary. A variety of definitions of major bleeding have been used in published clinical studies, and this diversity adds to the difficulty in comparing data between trials and in performing meta-analyses. In the first step towards unified definitions of bleeding complications, the definition of major bleeding in non-surgical patients was discussed at the Control of Anticoagulation Subcommittee of the International Society on Thrombosis and Haemostasis. Arising from that discussion, a definition was developed that should be applicable to studies with all agents that interfere with hemostasis, including anticoagulants, platelet function inhibitors and fibrinolytic drugs. The definition and the text that follows have been reviewed and approved by the cochairs of the subcommittee and the revised version is published here. The intention is to also seek approval of this definition from the regulatory authorities.
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            American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism

            Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), occurs in ∼1 to 2 individuals per 1000 each year, corresponding to ∼300 000 to 600 000 events in the United States annually. These evidence-based guidelines from the American Society of Hematology (ASH) intend to support patients, clinicians, and others in decisions about treatment of VTE. ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and adult patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment. The panel agreed on 28 recommendations for the initial management of VTE, primary treatment, secondary prevention, and treatment of recurrent VTE events. Strong recommendations include the use of thrombolytic therapy for patients with PE and hemodynamic compromise, use of an international normalized ratio (INR) range of 2.0 to 3.0 over a lower INR range for patients with VTE who use a vitamin K antagonist (VKA) for secondary prevention, and use of indefinite anticoagulation for patients with recurrent unprovoked VTE. Conditional recommendations include the preference for home treatment over hospital-based treatment for uncomplicated DVT and PE at low risk for complications and a preference for direct oral anticoagulants over VKA for primary treatment of VTE.
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              Oral apixaban for the treatment of acute venous thromboembolism.

              Apixaban, an oral factor Xa inhibitor administered in fixed doses, may simplify the treatment of venous thromboembolism. In this randomized, double-blind study, we compared apixaban (at a dose of 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months) with conventional therapy (subcutaneous enoxaparin, followed by warfarin) in 5395 patients with acute venous thromboembolism. The primary efficacy outcome was recurrent symptomatic venous thromboembolism or death related to venous thromboembolism. The principal safety outcomes were major bleeding alone and major bleeding plus clinically relevant nonmajor bleeding. The primary efficacy outcome occurred in 59 of 2609 patients (2.3%) in the apixaban group, as compared with 71 of 2635 (2.7%) in the conventional-therapy group (relative risk, 0.84; 95% confidence interval [CI], 0.60 to 1.18; difference in risk [apixaban minus conventional therapy], -0.4 percentage points; 95% CI, -1.3 to 0.4). Apixaban was noninferior to conventional therapy (P<0.001) for predefined upper limits of the 95% confidence intervals for both relative risk (<1.80) and difference in risk (<3.5 percentage points). Major bleeding occurred in 0.6% of patients who received apixaban and in 1.8% of those who received conventional therapy (relative risk, 0.31; 95% CI, 0.17 to 0.55; P<0.001 for superiority). The composite outcome of major bleeding and clinically relevant nonmajor bleeding occurred in 4.3% of the patients in the apixaban group, as compared with 9.7% of those in the conventional-therapy group (relative risk, 0.44; 95% CI, 0.36 to 0.55; P<0.001). Rates of other adverse events were similar in the two groups. A fixed-dose regimen of apixaban alone was noninferior to conventional therapy for the treatment of acute venous thromboembolism and was associated with significantly less bleeding (Funded by Pfizer and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00643201).
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                Author and article information

                Journal
                Int J Gen Med
                Int J Gen Med
                ijgm
                ijgm
                International Journal of General Medicine
                Dove
                1178-7074
                28 July 2021
                2021
                : 14
                : 4031-4037
                Affiliations
                [1 ]Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences , Riyadh, Saudi Arabia
                [2 ]King Abdullah International Medical Research Center , Riyadh, Saudi Arabia
                [3 ]Sales Department, SPIMACO Addwaeih , Riyadh, Saudi Arabia
                [4 ]Sales Department,Novo Nordisk , Riyadh, Saudi Arabia
                [5 ]Sales Department,Sanofi , Riyadh, Saudi Arabia
                [6 ]Sales Department, BAYER Pharmaceutical , Riyadh, Saudi Arabia
                [7 ]Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University , Jeddah, Saudi Arabia
                [8 ]Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University , Riyadh, Saudi Arabia
                [9 ]Department of Pharmacy Practice, College of Pharmacy, Qassim University , Qassim, Saudi Arabia
                [10 ]Drug Sector, Saudi Food and Drug Authority , Riyadh, Saudi Arabia
                [11 ]Department of Clinical Pharmacy, College of Pharmacy, King Saud University , Riyadh, Saudi Arabia
                Author notes
                Correspondence: Ghazwa B Korayem Pharmacy Practice Department, College of Pharmacy, Princess Nourah bint Abdulrahman University , Al Imam Abdullah Ibn Saud Ibn Abdul Aziz Road, Riyadh, Saudi ArabiaTel +966 504161649 Email Gbkorayem@pnu.edu.sa
                Author information
                http://orcid.org/0000-0003-2308-8407
                http://orcid.org/0000-0003-4291-2959
                http://orcid.org/0000-0002-2244-0491
                http://orcid.org/0000-0002-5162-5241
                http://orcid.org/0000-0002-3997-676X
                http://orcid.org/0000-0003-2022-5955
                http://orcid.org/0000-0002-3792-4106
                Article
                322221
                10.2147/IJGM.S322221
                8327475
                34349553
                df524efe-0e8d-49dd-9a36-2e79bb7e41d2
                © 2021 Al Yami et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 31 May 2021
                : 08 July 2021
                Page count
                Figures: 1, Tables: 6, References: 21, Pages: 7
                Funding
                Funded by: Researcher Supporting Project (RSP-2021/77);
                The author (OAA) received a fund from the Researcher Supporting Project (RSP-2021/77), King Saud University, Riyadh, Saudi Arabia, to support the publication of this article and the authors would like to extend their appreciation to King Saud University for funding the publication of this work. The funding agency had no role in designing the study, conducting the analysis, interpreting the data or writing the manuscript.
                Categories
                Original Research

                Medicine
                venous thromboembolism,vte,dvt,pe,bleeding,apixaban,doacs,warfarin
                Medicine
                venous thromboembolism, vte, dvt, pe, bleeding, apixaban, doacs, warfarin

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