Effects of apixaban: A Synthesis of Findings from 22 Studies

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Original Abstract of the Article

Major research findings

Several studies have investigated the effects of apixaban, a direct factor Xa inhibitor, and have yielded interesting findings regarding its efficacy and safety. 11 found that apixaban’s effects are not influenced by the use of interacting medications when compared to warfarin. This study revealed that using interacting medications with both apixaban and warfarin does not result in a significant change in the primary efficacy outcome of stroke or systemic embolism or the primary safety outcome of major bleeding.

5 evaluated the efficacy and safety of apixaban compared to enoxaparin using Bayesian meta-analysis. The results showed that apixaban did not demonstrate a clear superiority to enoxaparin in the composite outcome of efficacy, which included venous thromboembolism and death during follow-up. Additionally, the risk of major and total bleeding was similar between the two groups. The study concluded that apixaban is an oral alternative with similar efficacy and safety to existing anticoagulant therapies.

Furthermore, 14 explored the effects of administering anticancer agents concurrently with apixaban or dalteparin on recurrence and bleeding in patients with cancer-associated venous thromboembolism (VTE). While the pharmacological interaction between anticancer agents and direct oral anticoagulants is perceived as a concern, this study did not reach a definitive conclusion.

In a systematic comparison of apixaban versus enoxaparin in patients undergoing total knee arthroplasty (TKA), 1 found that apixaban was non-inferior to enoxaparin, with a significantly lower risk of major VTE and a lower major bleeding rate.

A meta-analysis of randomized controlled trials assessing the risk of myocardial infarction (MI) in patients receiving apixaban, 6 revealed that apixaban treatment was not associated with an increased risk of MI or mortality when compared to various control groups. The pooled risk of major bleeding was also lower in the apixaban treated groups.

A meta-analysis of randomized controlled trials comparing the risks of bleeding and all-cause mortality between apixaban and VKAs, 8 showed that apixaban was associated with a lower risk of bleeding compared to VKAs. It also found that apixaban was associated with a decreased risk of intracranial bleeding and all-cause mortality.

The study 12 investigated the interaction between apixaban and hemoglobin and its effects on plasma levels. The results suggest that apixaban binds to hemoglobin, which could potentially influence its free plasma levels.

Benefits and Risks

Benefit summary

Multiple studies have indicated that apixaban can effectively reduce the risk of thromboembolic events such as stroke and embolism. 11 , 3 , 8 Additionally, apixaban has shown potential to decrease the risk of death in patients with atrial fibrillation. 8 Notably, compared to conventional anticoagulants like warfarin, apixaban has been linked to a lower risk of bleeding. 11 , 8 Moreover, research has shown that apixaban significantly reduces the risk of major VTE and major bleeding in patients who have undergone total knee arthroplasty when compared to enoxaparin. 1

Risk summary

A primary risk associated with apixaban is the potential for bleeding. However, studies have generally shown that apixaban has a lower bleeding risk compared to traditional anticoagulants such as warfarin. 11 , 8 Additionally, apixaban’s binding to hemoglobin, which can affect its plasma concentration, is a factor to consider. 12

Comparison between studies

Commonalities in research

Several studies converge in their findings that apixaban effectively reduces the risk of thromboembolic events such as stroke and embolism. 11 , 3 , 8 Another consistent finding across these studies is that apixaban tends to have a lower bleeding risk than traditional anticoagulants like warfarin. 11 , 8

Differences in research

The specific medications used for comparison and the evaluated outcomes vary among the studies. For instance, 11 compared apixaban to warfarin, while 5 compared it to enoxaparin. The evaluated outcomes also varied, encompassing stroke and embolism, bleeding, death, and hospitalization rates depending on the research focus.

Consistency and contradictions in the results

The research findings consistently demonstrate that apixaban effectively reduces the risk of thromboembolic events, such as stroke and embolism, and potentially lowers the risk of death in patients with atrial fibrillation. 11 , 3 , 8 Additionally, there is a consistent trend across these studies indicating a lower bleeding risk with apixaban compared to traditional anticoagulants. 11 , 8 However, the direct comparison of study results can be challenging due to the variability in comparison medications and evaluated outcomes.

Considerations for real-world application

Apixaban has established itself as an effective medication for reducing the risk of stroke and embolism in patients with atrial fibrillation. 11 It’s important to acknowledge that apixaban’s use is not without potential risks, such as bleeding. 11 , 8 Prior to starting apixaban, it’s crucial to consult with a doctor to discuss its potential benefits and risks and to follow prescribed instructions carefully.

Limitations of current research

Many studies on apixaban are short-term trials, and research focusing on long-term effects and safety remains limited. The variations in patient populations and comparison medications across studies pose a challenge for direct comparisons of results. Further research is needed to comprehensively investigate apixaban’s impact on hemoglobin binding and its potential influence on drug efficacy. 12

Future research directions

Future research on apixaban should prioritize evaluating its long-term effects and safety, investigating its efficacy in diverse patient populations, and conducting in-depth analysis of its interaction with hemoglobin and potential impacts on drug efficacy.

Conclusion

Apixaban demonstrates effectiveness in reducing the risk of thromboembolic events such as stroke and embolism, and potentially lowers the risk of death in patients with atrial fibrillation. 11 , 3 , 8 Apixaban also tends to have a lower bleeding risk compared to traditional anticoagulants. 11 , 8 It’s crucial to consult with a doctor before starting apixaban and to follow prescribed instructions meticulously.

Literature analysis of 22 papers
Positive Content
22
Neutral Content
0
Negative Content
0
Article Type
8
5
0
1
22
1.

Apixaban versus enoxaparin in patients with total knee arthroplasty. A meta-analysis of randomised trials.

Author: HuangJiahao, CaoYunfei, LiaoCun, WuLiucheng, GaoFeng

Lower bleeding
VTE prevention
Bleeding
Mortality

The study found that apixaban is non-inferior to subcutaneous enoxaparin for the prevention of venous thromboembolism (VTE) after total knee arthroplasty (TKA). Apixaban was associated with a lower major bleeding rate than enoxaparin.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

2.

Apixaban and rivaroxaban safety after hip and knee arthroplasty: a meta-analysis.

Author: AlvesCarlos, Batel-MarquesFrancisco, MacedoAna Filipa

Reduced bleeding

A meta-analysis compared the safety of apixaban and rivaroxaban, two direct Xa coagulation factor inhibitors, in patients undergoing knee and hip arthroplasty. Apixaban was associated with fewer major and total bleeding events after knee arthroplasty compared to rivaroxaban, with no significant differences observed after hip arthroplasty.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation.

Author: WallentinLars, LopesRenato D, HannaMichael, ThomasLaine, HellkampAnne, NepalSunil, HylekElaine M, Al-KhatibSana M, AlexanderJohn H, AlingsMarco, AmerenaJohn, AnsellJack, AylwardPhilip, BartunekJozef, CommerfordPatrick, De CaterinaRaffaele, ErolCetin, HarjolaVeli-Pekka, HeldClaes, HorowitzJohn D, HuberKurt, HustedSteen, KeltaiMatyas, LanasFernando, LishengLiu, McMurrayJohn J V, OhByung-Hee, RosenqvistMårten, RuzylloWitold, StegPhilippe Gabriel, VinereanuDragos, XavierDenis, GrangerChristopher B,

Stroke reduction
Bleeding risk

This analysis of the ARISTOTLE trial, which compared apixaban to warfarin for stroke prevention in atrial fibrillation, examined treatment effects in relation to time in therapeutic range (TTR). The findings indicate that apixaban may provide benefits regardless of TTR, while warfarin's effectiveness is more dependent on TTR.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

The effects of apixaban on hospitalizations in patients with different types of atrial fibrillation: insights from the AVERROES trial.

Author: HohnloserStefan H, ShestakovskaOlga, EikelboomJohn, FranzosiMaria Grazia, TanRu San, ZhuJun, YusufSalim, ConnollyStuart J

Cardiovascular hospitalization reduction

Apixaban therapy was associated with a lower risk of cardiovascular hospitalization in patients with atrial fibrillation (AF), particularly for stroke and other cardiovascular causes.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

5.

Evaluating the efficacy and safety of apixaban, a new oral anticoagulant, using Bayesian meta-analysis.

Author: VillaLorenzo A, MaloneDaniel C, RossDaniel

Thromboembolism treatment
Bleeding events

Apixaban, a direct factor Xa inhibitor, showed similar efficacy and safety to enoxaparin for the treatment of acute venous thromboembolism. While both agents demonstrated effectiveness in preventing venous thromboembolism, there was no clear superiority of apixaban over enoxaparin.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

6.

Apixaban and risk of myocardial infarction: meta-analysis of randomized controlled trials.

Author: TornyosAdrienn, VorobcsukAndrás, KupóPéter, AradiDániel, KehlDániel, KomócsiAndrás

MI prevention
Bleeding risk

This systematic review evaluated the risk of myocardial infarction (MI) and mortality in patients receiving apixaban, a new-generation oral anti-Xa agent. Pooled results showed no increase in the risk of MI or mortality in apixaban-treated patients compared to control groups.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial.

Author: HeldClaes, HylekElaine M, AlexanderJohn H, HannaMichael, LopesRenato D, WojdylaDaniel M, ThomasLaine, Al-KhalidiHussein, AlingsMarco, XavierDennis, AnsellJack, GotoShinya, RuzylloWitold, RosenqvistMårten, VerheugtFreek W A, ZhuJun, GrangerChristopher B, WallentinLars

Atrial fibrillation treatment
Stroke prevention
Major bleed

This ancillary study evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

A meta-analysis of randomized controlled trials of the risk of bleeding with apixaban versus vitamin K antagonists.

Author: ToumaLahoud, FilionKristian B, AtallahRenée, EbergMaria, EisenbergMark J

All-cause mortality reduction
Apixaban effectiveness
Bleeding risk reduction

This meta-analysis compared the risks of bleeding and all-cause mortality between apixaban and vitamin K antagonists (VKAs) for stroke prevention, knee replacement surgery, and venous thromboembolism. Apixaban was associated with a lower risk of bleeding and all-cause mortality.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

9.

Apixaban Reduces Hospitalizations in Patients With Venous Thromboembolism: An Analysis of the Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy (AMPLIFY) Trial.

Author: LiuXianchen, JohnsonMargot, MardekianJack, PhatakHemant, ThompsonJohn, CohenAlexander T

Reduced bleeding
Reduced hospitalization

Apixaban, a direct oral anticoagulant, was noninferior to enoxaparin/warfarin in preventing recurrent venous thromboembolism (VTE) or VTE-related death in the AMPLIFY trial. Apixaban was also associated with significantly less bleeding. This analysis found that apixaban led to fewer all-cause hospitalizations than enoxaparin/warfarin.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial.

Author: Jaspers FocksJeroen, BrouwerMarc A, WojdylaDaniel M, ThomasLaine, LopesRenato D, WashamJeffrey B, LanasFernando, XavierDenis, HustedSteen, WallentinLars, AlexanderJohn H, GrangerChristopher B, VerheugtFreek W A

Apixaban effective
Apixaban safe
Increased bleeding
Increased mortality
Increased thromboembolic

Apixaban is more effective than warfarin in reducing the risk of stroke and systemic embolism in patients with atrial fibrillation and polypharmacy. Apixaban is as safe as warfarin in this patient population.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

11.

Interacting medication use and the treatment effects of apixaban versus warfarin: results from the ARISTOTLE Trial.

Author: WashamJeffrey B, HohnloserStefan H, LopesRenato D, WojdylaDaniel M, VinereanuDragos, AlexanderJohn H, GershBernard J, HannaMichael, HorowitzJohn, HylekElaine M, XavierDenis, VerheugtFreek W A, WallentinLars, GrangerChristopher B,

Stroke prevention
Systemic embolism prevention
Major bleeding

Interacting medications did not significantly affect the efficacy or safety of apixaban compared to warfarin in patients with atrial fibrillation.

Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

12.

Apixaban Interacts with Haemoglobin: Effects on Its Plasma Levels.

Author: SaccoMonica, LancellottiStefano, BerrutiFederico, ArcovitoAlessandro, BellelliAndrea, RicciardelliTiziana, AutieroIda, CavalloLuigi, OlivaRomina, De CristofaroRaimondo

Apixaban, a blood thinner, binds to hemoglobin in the blood, which may affect its effectiveness.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

14.

Effects of concomitant administration of anticancer agents and apixaban or dalteparin on recurrence and bleeding in patients with cancer-associated venous thromboembolism.

Author: VersoMelina, MunozAndres, BauersachsRupert, HuismanMenno V, MandalàMario, VescovoGiorgio, BecattiniCecilia, AgnelliGiancarlo

Cancer-associated VTE treatment
Pharmacological interaction

This review discusses the potential for interactions between anticancer agents and oral anticoagulants in patients with cancer-associated venous thromboembolism (VTE).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

15.

Effects of thromboprophylactic doses of apixaban and rivaroxaban on coagulation and thrombin generation in association with total hip replacement.

Author: HelinTuukka A, VirtanenLauri, ManninenMikko, LeskinenJarkko, LeppilahtiJuhana, Joutsi-KorhonenLotta, LassilaRiitta

Thromboprophylaxis

Apixaban and rivaroxaban distinctly inhibited thrombin generation under postoperative conditions after total hip arthroplasty, with rivaroxaban showing a more pronounced and sustained effect.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

18.

Evaluation of the Antithrombotic Effects of Rivaroxaban and Apixaban Using the Total Thrombus-Formation Analysis System<sup>&#174;</sup>: <i>In Vitro</i> and <i>Ex Vivo</i> Studies.

Author: SugiharaHidekazu, IdemotoYoshiaki, KuwanoTakashi, NagataYoshihisa, MoriiJoji, SugiharaMakoto, OgawaMasahiro, MiuraShin-Ichiro, SakuKeijiro

NOAC monitoring

This study addresses the usefulness of the Total Thrombus-Formation Analysis System<sup>&#174;</sup> (T-TAS<sup>&#174;</sup>) for monitoring the anticoagulant effects of non-vitamin K oral anticoagulants (NOACs) in clinical practice.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

19.

In vitro effects of Gla-domainless factor Xa analog on procoagulant and fibrinolytic pathways in apixaban-treated plasma and whole blood.

Author: TeradaRui, JohnsonPenny M, ButtAmir L, MishimaYuko, StewartKenneth E, LevyJerold H, TanakaKenichi A

FXa inhibitor reversal

Andexanet alfa is an antidote to FXa inhibitors, but its effects on anti-Xa reversal and fibrinolysis have not been studied. This research used a GDXa analog to model the interaction between andexanet and apixaban.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

21.

Extended Treatment with Apixaban for Venous Thromboembolism Prevention in the Netherlands: Clinical and Economic Effects.

Author: de JongLisa A, Gout-ZwartJudith J, StevanovicJelena, RilaHarrie, KoopsMike, HuismanMenno V, PostmaMaarten J

Apixaban effectiveness
Extended anticoagulant treatment
Venous thromboembolism

Extended treatment with apixaban was cost-effective for the prevention of recurrent venous thromboembolism (VTE) in Dutch patients.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

22.

Interacting medication use and the treatment effects of apixaban versus warfarin: results from the ARISTOTLE Trial.

Author: WashamJeffrey B, HohnloserStefan H, LopesRenato D, WojdylaDaniel M, VinereanuDragos, AlexanderJohn H, GershBernard J, HannaMichael, HorowitzJohn, HylekElaine M, XavierDenis, VerheugtFreek W A, WallentinLars, GrangerChristopher B,

Stroke prevention
Systemic embolism prevention
Major bleeding

Interacting medications did not significantly affect the efficacy or safety of apixaban compared to warfarin in patients with atrial fibrillation.

Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

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