Apixaban vs Rivaroxaban for Atrial Fibrillation

(VALIANT-AF-T Trial)

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two blood thinners, apixaban and rivaroxaban, to determine which better prevents strokes in people with atrial fibrillation (an irregular and often rapid heart rate). Researchers will examine stroke, major bleeding, and death rates among approximately 10,000 veteran patients. The trial will span about 7 years, but it won't require regular visits, as data will be collected from medical records. Individuals diagnosed with atrial fibrillation who can take oral medication may be suitable for this trial. As a Phase 4 trial, this research aims to understand how these FDA-approved and effective treatments can benefit more patients.

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 is the safety track record for these treatments?

A previous study showed that apixaban carries a lower risk of major bleeding compared to other blood thinners. Another study found that apixaban had better safety results than rivaroxaban. However, a higher dose of apixaban can increase the risk of bleeding in individuals with severe kidney problems.

Research indicates that rivaroxaban generally has low rates of serious issues, such as stroke or bleeding. Yet, another study noted that rivaroxaban might have a higher risk of major bleeding compared to apixaban.

Both drugs are widely used and approved for treating atrial fibrillation, an irregular heartbeat, and are considered safe for most people. Consulting a doctor is important to determine which drug might be better for individual needs. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because Apixaban and Rivaroxaban offer different dosing options and safety profiles for managing atrial fibrillation compared to traditional anticoagulants like warfarin. Apixaban is unique because it is taken twice daily, which can provide more stable blood levels and potentially less bleeding risk, especially with its option for a reduced dose for certain patients. Rivaroxaban, taken once daily, simplifies the dosing schedule and also offers a reduced dose for those with decreased kidney function, making it an appealing option for patients who might struggle with more frequent dosing. Both drugs eliminate the need for regular blood monitoring, which is a significant advantage over warfarin, making them convenient and potentially safer options for patients.

What evidence suggests that this trial's treatments could be effective for atrial fibrillation?

This trial will compare Apixaban and Rivaroxaban for their effectiveness in preventing strokes in people with atrial fibrillation (A Fib). Participants in the Apixaban Arm will receive twice-daily oral doses of apixaban, while those in the Rivaroxaban Arm will receive daily oral doses of rivaroxaban.

Studies have shown that both apixaban and rivaroxaban effectively thin the blood to prevent strokes in people with A Fib. Apixaban is associated with a lower risk of major bleeding compared to some other blood thinners, making it a safer option for certain patients. Research also shows that apixaban reduces the risk of stroke or blood clots more effectively than aspirin in people with A Fib.

Rivaroxaban is effective for long-term stroke prevention and remains effective even at lower doses. However, some studies suggest it might carry a slightly higher risk of causing bleeding than apixaban. Overall, both drugs are effective, but the best choice depends on individual health factors and risks. ^{2 5 6 7 8}

Who Is on the 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

Are You a Good Fit for This Trial?

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

CHADS2VASc >=3

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9267894/

Effectiveness and Safety of Apixaban in over 3.9 Million ... Apixaban was associated with a significantly lower risk of major bleeding compared to VKAs (RR 0.58, 95% CI 0.52–0.65, I2 = 90%), dabigatran (RR ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2310234

Apixaban for Stroke Prevention in Subclinical Atrial ... Conclusions. Among patients with subclinical atrial fibrillation, apixaban resulted in a lower risk of stroke or systemic embolism than aspirin ...

3. jacc.org jacc.org/doi/10.1016/j.jacadv.2025.101714

A Comparison of Outcomes With Apixaban, Rivaroxaban ... We observed that bleeding was highest with rivaroxaban, followed by warfarin, and then apixaban. Rates of thrombosis were higher with apixaban than with ...

4. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.065614

Associations of Apixaban Dose With Safety and ... Compared with 2.5 mg, use of 5 mg apixaban was associated with a higher risk of bleeding in patients with atrial fibrillation and severe chronic kidney disease.

5. academic.oup.com academic.oup.com/ehjcvp/article/11/5/403/8088415

Apixaban outcomes in atrial fibrillation patients with a single ... The primary effectiveness outcome was stroke/systemic embolism (SSE), and the primary safety outcome was major bleeding. Of 1944 patients (mean age 74.3 ± 7.9 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31902123/

Safety outcomes of apixaban in patients with nonvalvular ... The primary endpoint was major bleeding in patients taking apixaban 5 mg. Secondary endpoints included major bleeding with apixaban 2.5 mg and minor bleeding in ...

7. ahajournals.org ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.123.065614?doi=10.1161/CIRCULATIONAHA.123.065614

Associations of Apixaban Dose With Safety and ... Compared with 2.5 mg, use of 5 mg apixaban was associated with a higher risk of bleeding in patients with atrial fibrillation and severe chronic kidney disease.

8. jacc.org jacc.org/doi/10.1016/S0735-1097%2825%2900546-7

COMPARATIVE SAFETY AND EFFICACY OF APIXABAN ... Our results indicate that apixaban is associated with better safety outcomes as compared to rivaroxaban without any difference in efficacy.