Apixaban vs Rivaroxaban for Atrial Fibrillation

(VALIANT-AF-T Trial)

Recruiting in Boston (>99 mi)

Overseen By Mustabeen Ashfaq, MS

Age: 65+

Sex: Any

Trial Phase: Phase 4

Sponsor: VA Office of Research and Development

Must be taking: Apixaban, Rivaroxaban

Must not be taking: Ritonavir, Itraconazole, Ketoconazole

Disqualifiers: Pregnancy, Bleeding diathesis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 3 years

10000 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be able to switch to the study medication, either apixaban or rivaroxaban, if you are currently using another anticoagulant.

What data supports the effectiveness of the drugs Apixaban and Rivaroxaban for atrial fibrillation?

Research shows that Apixaban is associated with a lower risk of stroke and major bleeding compared to Rivaroxaban in patients with atrial fibrillation. This suggests that Apixaban might be a safer option for preventing stroke in these patients. ^{1 2 3 4 5}

Is Apixaban safer than Rivaroxaban for atrial fibrillation?

Research shows that Apixaban generally has a lower risk of major bleeding compared to Rivaroxaban in patients with atrial fibrillation. This suggests that Apixaban may have a more favorable safety profile. ^{6 7 8 9 10}

How do apixaban and rivaroxaban differ in treating atrial fibrillation?

Apixaban is associated with a lower risk of stroke and major bleeding compared to rivaroxaban in patients with atrial fibrillation, making it potentially safer while maintaining effectiveness. ^{1 5 7 11 12}

What is the purpose of this trial?

* The trial will compare two anticoagulants ("blood thinners") that are currently used in the VA and are considered standard care to prevent strokes in patients with atrial fibrillation. The two most commonly-used anticoagulants will be compared: apixaban (Eliquis) and rivaroxaban (Xarelto). They are considered by many doctors to have similar benefits and risks, but no one knows for sure. * The trial only enrolls patients with a diagnosis of atrial fibrillation ("A Fib"). * We will measure, in about 10,000 VA patients nationally, whether the rates of stroke, major bleeding, or death differ between these two drugs. * The trial will last about 7 years, but after the first prescription, all information will be collected from electronic medical records.

Research Team

Cara N Pellegrini

Principal Investigator

San Francisco VA Medical Center, San Francisco, CA

William E. Boden, MD

Principal Investigator

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Eligibility Criteria

This trial is for patients with atrial fibrillation, a heart condition that increases stroke risk. It's open to around 10,000 VA patients who will be monitored over 7 years through their medical records.

Inclusion Criteria

I can take pills and will follow the blood thinner plan as directed.

CHADS2VASc >=3

I am a Veteran aged 22 or older.

Exclusion Criteria

I cannot take blood thinners in pill form due to health reasons.

Pregnancy or lactation

Mechanical heart valve

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 3 months

1 visit (in-person)

Treatment

Participants are randomized to receive either apixaban or rivaroxaban, with clinical management per providers and data collected remotely

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, with data collected remotely

3 years

Data Analysis

Completion of data analysis after the follow-up period

1 year

Treatment Details

Interventions

• Apixaban
• Rivaroxaban

Trial Overview The study compares two standard blood thinners used in the VA: Apixaban (Eliquis) and Rivaroxaban (Xarelto). It aims to determine if there's a difference in the rates of stroke, major bleeding, or death between these drugs.

Participant Groups

Group I: Rivaroxaban Arm Active Control 1 Intervention

Study participants will be randomized to daily oral administration of rivaroxaban 20mg. Reduced dose rivaroxaban (15 mg once daily) will be given to participants with a creatinine clearance 15-50 mL/min.

Group II: Apixaban Arm Active Control 1 Intervention

Study participants will be randomized to twice daily oral administration of apixaban 5mg. Reduced dose apixaban (2.5 mg twice daily) will be given to participants who meet 2 of the 3 criteria: age 80 years, body weight 60 kg, and serum creatinine 1.5 mg/dL.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

U.S. Food and Drug Administration (FDA)

Collaborator

Trials

2

Recruited

470+

Findings from Research

In a study of 600 patients treated for acute venous thromboembolism (VTE), both apixaban and rivaroxaban showed comparable efficacy, with low rates of VTE recurrence (2.3% for apixaban and 2% for rivaroxaban).

Apixaban was associated with a significantly lower rate of clinically relevant nonmajor bleeding (2.3%) compared to rivaroxaban (6.7%), suggesting it may be a safer option in terms of bleeding complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apixaban and Rivaroxaban in Patients With Acute Venous Thromboembolism. Bott-Kitslaar, DM., McBane, RD., Casanegra, AI., et al.[2020]

A study involving 91 patients and 184 samples found that apixaban and rivaroxaban levels in plasma can be effectively monitored using conventional tests like PT and dRVVT, indicating their reliability for assessing anticoagulant effects.

The established on-therapy ranges for both apixaban and rivaroxaban provide valuable benchmarks for clinicians to ensure effective and safe dosing in patients undergoing treatment with these direct oral anticoagulants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of global laboratory methods and establishing on-therapy ranges for monitoring apixaban and rivaroxaban: Experience at a single institution. Park, SH., Seo, YH., Park, PW., et al.[2021]

Dabigatran, rivaroxaban, and apixaban have rapidly gained popularity in clinical practice for treating atrial fibrillation, making up 62% of new prescriptions by the end of the study period, which included 6893 patients from 2010 to 2013.

However, patients initiating these novel anticoagulants faced significantly higher costs, with an average increase of over $900 in combined spending for the first 6 months compared to those starting warfarin, highlighting the financial impact of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of initiation of oral anticoagulants in patients with atrial fibrillation- quality and cost implications. Desai, NR., Krumme, AA., Schneeweiss, S., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Meta-Analysis Comparing Apixaban Versus Rivaroxaban for Management of Patients With Nonvalvular Atrial Fibrillation. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Apixaban and Rivaroxaban in Patients With Acute Venous Thromboembolism. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Evaluation of global laboratory methods and establishing on-therapy ranges for monitoring apixaban and rivaroxaban: Experience at a single institution. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Association of Rivaroxaban vs Apixaban With Major Ischemic or Hemorrhagic Events in Patients With Atrial Fibrillation. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Head-to-head efficacy and safety of rivaroxaban, apixaban, and dabigatran in an observational nationwide targeted trial. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Direct comparative effectiveness and safety between non-vitamin K antagonist oral anticoagulants for stroke prevention in nonvalvular atrial fibrillation: a systematic review and meta-analysis of observational studies. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of apixaban versus rivaroxaban for prevention of recurrent venous thromboembolism and adverse bleeding events in patients with venous thromboembolism: a retrospective population-based cohort analysis. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Real-world evidence comparing oral anticoagulants in non-valvular atrial fibrillation: a systematic review and network meta-analysis. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Real-world comparison of bleeding risks among non-valvular atrial fibrillation patients prescribed apixaban, dabigatran, or rivaroxaban. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Real-world evidence of stroke prevention in patients with nonvalvular atrial fibrillation in the United States: the REVISIT-US study. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Patterns of initiation of oral anticoagulants in patients with atrial fibrillation- quality and cost implications. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Primary and secondary prevention with new oral anticoagulant drugs for stroke prevention in atrial fibrillation: indirect comparison analysis. [2021]