Blood Thinners for Atrial Fibrillation

(ASPIRE-AF Trial)

Recruiting at103 trial locations

Overseen by David Conen, MD, MPH

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Population Health Research Institute

Must not be taking: Anticoagulants, Dual antiplatelets

Disqualifiers: Chronic AF, Severe renal insufficiency, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing whether taking blood-thinning pills can prevent strokes and other heart issues in patients who have temporary irregular heartbeats and are at risk of stroke after surgery. These pills are a recent breakthrough in preventing strokes.

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 data supports the effectiveness of the drug Apixaban, Eliquis, Dabigatran, Pradaxa, Prazaxa, BIBR-953, BIBR-1048, Edoxaban, Savaysa, DU-176, DU-176b, Edoxaban tosilate hydrate, Edoxaban tosylate, LIXIANA, Lixiana, Lixiana OD, Roteas, Rivaroxaban, Xarelto for atrial fibrillation?

Research shows that new oral anticoagulants like apixaban, dabigatran, edoxaban, and rivaroxaban are effective in preventing strokes in patients with atrial fibrillation. These drugs are as effective as warfarin but have fewer major bleeding risks and do not require regular blood monitoring. ^{1 2 3 4 5}

Is it safe to use blood thinners like Apixaban, Dabigatran, Edoxaban, and Rivaroxaban for atrial fibrillation?

Blood thinners like Apixaban, Dabigatran, Edoxaban, and Rivaroxaban have been studied for safety in humans. They are generally well tolerated, with a lower risk of major bleeding compared to some older treatments. However, they can still cause bleeding, and specific measures are recommended to manage bleeding complications. ^{1 2 6 7 8}

How do these drugs for atrial fibrillation differ from other treatments?

These drugs, including Apixaban, Dabigatran, Edoxaban, and Rivaroxaban, are unique because they do not require regular blood monitoring like warfarin, making them more convenient for patients. They also have different ways of being processed by the body, with some being excreted by the kidneys and others by the liver, which can influence their suitability for different patients. ^{1 2 9 10 11}

Research Team

David Conen, MD, MPH

Principal Investigator

Population Health Research Institute

PJ Devereaux, MD, PhD

Principal Investigator

Population Health Research Institute

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Apixaban (Anticoagulant)
• Dabigatran (Anticoagulant)
• Edoxaban (Anticoagulant)
• Rivaroxaban (Anticoagulant)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Population Health Research Institute

Lead Sponsor

Trials

165

Recruited

717,000+

Dr. Salim Yusuf

Population Health Research Institute

Chief Executive Officer since 2001

MD, McMaster University

Dr. Sonia Anand

Population Health Research Institute

Chief Medical Officer since 2015

MD, McMaster University

Hamilton Health Sciences Corporation

Collaborator

Trials

380

Recruited

345,000+

Dr. Craig A. VanHelder

Hamilton Health Sciences Corporation

Chief Medical Officer since 2023

MD

Tracey MacArthur

Hamilton Health Sciences Corporation

Chief Executive Officer

MSc in Quality Improvement & Patient Safety from the University of Toronto, Honours BA in Psychology from the University of Waterloo, Masters Certificate in Project Management from the Schulich School of Business at York University

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Perioperative management and therapy of bleeding complications]. [2022]

2. Netherlands 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. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

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

4. New Zealand 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. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Incorporating edoxaban into the choice of anticoagulants for atrial fibrillation. [2016]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Apixaban: A Review in Venous Thromboembolism. [2020]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Evaluating the Effectiveness of Apixaban Additional Risk Minimisation Measures Using Surveys in Europe. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Apixaban: first global approval. [2021]

9. United States 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. [2013]

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

Systematic review and adjusted indirect comparison meta-analysis of oral anticoagulants in atrial fibrillation. [2018]

11. New Zealand 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. [2021]