Blood Thinners for Atrial Fibrillation

(ASPIRE-AF Trial)

Recruiting at 133 trial locations

Overseen By Cassie McDonald

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Population Health Research Institute

Must not be taking: Anticoagulants, Dual antiplatelets

Disqualifiers: Chronic AF, Severe renal insufficiency, 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: Unknown

Duration: 24 months

2270 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether blood thinners can prevent strokes and other heart problems in individuals who experienced temporary atrial fibrillation (an irregular heartbeat) after non-cardiac surgery. Participants will receive one of four blood thinners—Apixaban (Eliquis), Dabigatran (Pradaxa), Edoxaban (Savaysa), or Rivaroxaban (Xarelto)—or no blood thinner to determine which option is safer and more effective. The trial seeks participants who had surgery in the last 35 days and experienced an irregular heartbeat afterward, along with other risk factors such as heart disease or recent major surgeries. As a Phase 4 trial, this research involves FDA-approved treatments and aims to understand their benefits for more patients, offering a chance to contribute to valuable insights.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you need long-term anticoagulation or dual antiplatelet treatment, you cannot participate in this trial.

What is the safety track record for these treatments?

Research shows that these blood thinners—Apixaban, Dabigatran, Edoxaban, and Rivaroxaban—are generally well-tolerated, but each has specific safety considerations.

Studies have found that Apixaban carries a lower risk of major bleeding compared to other blood thinners like warfarin and Dabigatran, resulting in fewer serious bleeding issues for patients.

Dabigatran has been linked to reports of serious bleeding, yet it significantly reduces stroke risk. Patients using Dabigatran require monitoring for bleeding risks.

Edoxaban effectively reduces stroke risk but presents a higher chance of major bleeding compared to some other options, necessitating a careful evaluation of benefits and risks.

Rivaroxaban has a mixed safety profile. It prevents strokes at a rate similar to other options, but the risk of major bleeding is higher than with Apixaban, though lower than with warfarin, a traditional blood thinner.

Overall, these treatments are well-researched and can be safe with proper medical guidance. Participants should consult their doctors to determine the best option for them. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they are part of a group known as non-vitamin K oral anticoagulants (NOACs), which offer some advantages over traditional blood thinners like warfarin. Unlike warfarin, which requires regular blood tests and dietary restrictions, NOACs such as Apixaban, Dabigatran, Edoxaban, and Rivaroxaban provide a more convenient option with fewer dietary limitations and no need for frequent monitoring. Furthermore, these NOACs have a rapid onset of action and a predictable anticoagulant effect, reducing the risk of stroke in patients with atrial fibrillation without the complexity of managing vitamin K levels. These features make NOACs a promising alternative for patients seeking effective and user-friendly anticoagulation therapy.

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

Research shows that Apixaban, Dabigatran, Edoxaban, and Rivaroxaban, part of the non-vitamin K oral anticoagulant (NOAC) treatment arm in this trial, effectively prevent strokes in people with atrial fibrillation, an irregular heartbeat. Apixaban reduces the risk of stroke or blood clots more effectively than aspirin or warfarin. Dabigatran lowers the risk of both types of strokes—those caused by blood blockages and those caused by bleeding—compared to warfarin. Edoxaban reduced the risk of stroke or blood clots by 66% compared to a placebo. Rivaroxaban also lowers the risk of stroke and blood clots in patients with nonvalvular atrial fibrillation. Studies have proven these treatments effective in protecting against strokes. ^{2 3 4 5 6}

Who Is on the Research Team?

David Conen, MD, MPH

Principal Investigator

Population Health Research Institute

PJ Devereaux, MD, PhD

Principal Investigator

Population Health Research Institute

Are You a Good Fit for This Trial?

This trial is for people aged 55-74 with cardiovascular disease, recent major vascular surgery, or a high stroke risk score; or those over 75. Participants must have had noncardiac surgery within the last 35 days and experienced at least one episode of atrial fibrillation afterward. It's not for individuals who need long-term antiplatelet treatment, have contraindications to oral anticoagulants, severe kidney issues, bleeding disorders, are pregnant without contraception use, or have a life expectancy under one year.

Inclusion Criteria

Your heart should be beating normally when you join the study.

I had surgery (not heart surgery) and stayed in the hospital overnight within the last 35 days.

I am 55-74 with heart disease or a high stroke risk score, or I am 75 or older.

Exclusion Criteria

I have a bleeding disorder.

My kidney function is severely reduced.

I had heart surgery within the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either non-vitamin K oral anticoagulants (NOACs) or no anticoagulation for stroke prevention

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Apixaban
• Dabigatran
• Edoxaban
• Rivaroxaban

Trial Overview

The study tests if taking a Non-vitamin K oral anticoagulant (NOAC) can prevent strokes and other heart problems in patients who've had temporary atrial fibrillation after non-heart-related surgery compared to no blood thinning treatment.

How Is the Trial Designed?

Group I: Non-vitamin K oral anticoagulant (NOAC) Experimental Treatment 1 Intervention

Participants randomized to the intervention arm will be prescribed one of the following NOACs for the duration of follow-up, unless they are undergoing a procedure with an increased risk of bleeding, have an adverse event or low calculated creatinine clearance, or decide to discontinue their use.

Group II: No anticoagulation Active Control 1 Intervention

Participants randomized to the control arm will not be prescribed an oral anticoagulant unless they develop a clear indication for one during follow-up (e.g., recurrent nonoperative AF). They can be newly prescribed or continue taking low dose aspirin or another single antiplatelet agent as per the protocol. This will be decided by the participant's physician.

Apixaban is already approved in European Union, United States for the following indications:

Approved in European Union as Eliquis for:

• Deep vein thrombosis
• Pulmonary embolism
• Nonvalvular atrial fibrillation

Approved in United States as Eliquis for:

• Deep vein thrombosis
• Pulmonary embolism
• Nonvalvular atrial fibrillation
• Stroke prevention

Who Is Running the Clinical Trial?

Population Health Research Institute

Lead Sponsor

Trials

165

Recruited

717,000+

Hamilton Health Sciences Corporation

Collaborator

Trials

380

Recruited

345,000+

Published Research Related to This Trial

In a study of 21,038 atrial fibrillation patients in Germany, edoxaban was found to be more effective than other oral anticoagulants, showing significantly lower risks of ischemic stroke or systemic embolism compared to apixaban, dabigatran, rivaroxaban, and vitamin K antagonists.

Edoxaban also exhibited a favorable safety profile, with lower risks of major bleeding compared to rivaroxaban and vitamin K antagonists, while showing similar bleeding risks to apixaban and dabigatran.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of clinical outcomes of edoxaban versus apixaban, dabigatran, rivaroxaban, and vitamin K antagonists in patients with atrial fibrillation in Germany: A real-world cohort study. Marston, XL., Wang, R., Yeh, YC., et al.[2022]

Apixaban, an oral direct factor Xa inhibitor, has been approved in the EU for preventing venous thromboembolism (VTE) after hip or knee replacement surgeries, demonstrating its efficacy in reducing the risk of blood clots in these patients.

The drug is also undergoing phase III trials for preventing strokes in patients with atrial fibrillation, indicating its potential for broader applications in thrombotic disorders, although development for acute coronary syndromes has been halted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apixaban: first global approval. Watson, J., Whiteside, G., Perry, C.[2021]

Oral anticoagulation therapy can reduce the risk of cardioembolic stroke in patients with atrial fibrillation (AF) by over 50%, highlighting its efficacy in preventing serious complications associated with AF.

New direct oral anticoagulants like rivaroxaban, apixaban, edoxaban, and dabigatran were developed to improve patient adherence and quality of life compared to traditional vitamin K antagonists, although models for optimizing their safe and effective use are still needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New oral anticoagulants in patients with nonvalvular atrial fibrillation: a review of pharmacokinetics, safety, efficacy, quality of life, and cost effectiveness. Mani, H., Lindhoff-Last, E.[2022]

Healthcare professionals (HCPs) and patients demonstrated satisfactory knowledge of bleeding risks associated with apixaban, with 96.1% of HCPs recognizing symptoms that require immediate attention and 71.2% of patients identifying abnormal bleeding as a significant side effect.

The study found that a significant majority of HCPs (97.8%) who received the Prescriber Guide utilized it in patient discussions, and 90.9% of patients who received the Patient Alert Card read it at least once, indicating effective distribution and utilization of these educational materials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the Effectiveness of Apixaban Additional Risk Minimisation Measures Using Surveys in Europe. Mayall, S., Kahlon, R., Al-Dakkak, I., et al.[2021]

In a meta-analysis of 44,733 patients with atrial fibrillation, dabigatran was found to significantly reduce the risk of composite outcomes like stroke or systemic embolism compared to rivaroxaban, indicating its potential efficacy in preventing serious complications.

Apixaban demonstrated a lower risk of major and gastrointestinal bleeding compared to both dabigatran and rivaroxaban, although it was associated with an increased risk of systemic emboli when compared to rivaroxaban, highlighting important safety considerations in choosing anticoagulants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review and adjusted indirect comparison meta-analysis of oral anticoagulants in atrial fibrillation. Baker, WL., Phung, OJ.[2018]

The new oral anticoagulants, including dabigatran, rivaroxaban, apixaban, and edoxaban, are effective for preventing blood clots after surgeries and in conditions like atrial fibrillation, with half-lives ranging from 8 to 17 hours, allowing for shorter cessation before surgery compared to traditional anticoagulants like warfarin.

In cases of acute bleeding, dabigatran can be removed from the body through hemodialysis, while rivaroxaban and apixaban cannot be dialyzed due to their high protein binding, highlighting the importance of specific management strategies for each anticoagulant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Perioperative management and therapy of bleeding complications]. von Heymann, C., Kaufner, L., Körber, M.[2022]

The ENGAGE AF study shows that edoxaban is as effective as warfarin in preventing strokes and systemic embolic events in patients with nonvalvular atrial fibrillation, while also significantly reducing the risk of major bleeding, including intracranial bleeding.

Edoxaban offers a net clinical benefit over warfarin, making it a strong option among non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention, alongside other medications like dabigatran, rivaroxaban, and apixaban.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incorporating edoxaban into the choice of anticoagulants for atrial fibrillation. Weitz, JI., Eikelboom, J.[2016]

Apixaban is an effective oral anticoagulant for treating and preventing venous thromboembolism (VTE), showing noninferiority to the traditional enoxaparin/warfarin treatment in large phase III trials over 6 months.

It has a lower risk of major bleeding compared to enoxaparin/warfarin and is well tolerated, making it a safer alternative for patients with VTE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apixaban: A Review in Venous Thromboembolism. Greig, SL., Garnock-Jones, KP.[2020]

In a study involving 60 patients undergoing atrial fibrillation ablation, rivaroxaban was associated with a significantly greater increase in D-dimer levels post-procedure compared to dabigatran, indicating a potential risk of hypercoagulability with rivaroxaban.

Despite the differences in D-dimer levels, the rates of rebleeding from the access site were similar for both anticoagulants, suggesting that both medications have comparable safety profiles in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A head-to-head comparison of periprocedural coagulability under anticoagulation with rivaroxaban versus dabigatran in patients undergoing ablation of atrial fibrillation. Sairaku, A., Yoshida, Y., Ando, M., et al.[2021]

In the ENGAGE AF-TIMI 48 trial involving patients with nonvalvular atrial fibrillation, edoxaban was found to be noninferior to warfarin in preventing strokes and systemic embolic events over a median treatment duration of 907 days.

Edoxaban demonstrated a significantly lower risk of major bleeding and cardiovascular-related deaths compared to warfarin, making it a safer and effective oral anticoagulant option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Edoxaban: a review in nonvalvular atrial fibrillation. McCormack, PL.[2016]

Newer anticoagulants like dabigatran, rivaroxaban, and apixaban are at least as effective as warfarin for preventing strokes in patients with atrial fibrillation, without the need for regular blood monitoring.

When treating older adults with atrial fibrillation, clinicians should consider factors such as patient tolerance, cost, adherence, and the absence of a reversal agent for these newer medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moving beyond warfarin-are we ready? A Review of the efficacy and safety of novel anticoagulant agents compared to warfarin for the management of atrial fibrillation in older adults. Ogbonna, KC., Clifford, KM.[2013]

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4.

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6.

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pubmed.ncbi.nlm.nih.gov/35807073/

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 ...