Anticoagulants vs Antiplatelets for Blood Clot Prevention After Heart Procedure

(ANDES Trial)

Overseen By Josep Rodes-Cabau

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Disqualifiers: End-stage renal disease, Recent stents, Prior intracranial hemorrhage, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

510 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have absolute contraindications (reasons not to use) for anticoagulation or antiplatelet therapy, you may not be eligible to participate.

What evidence supports the effectiveness of the drugs used for blood clot prevention after a heart procedure?

The drugs rivaroxaban, apixaban, and edoxaban have been shown to be effective in preventing blood clots after major surgeries like hip and knee replacements, and in preventing strokes in patients with atrial fibrillation. Rivaroxaban is also effective in treating deep vein thrombosis and preventing pulmonary embolism. ^{1 2 3 4 5}

Is the treatment with anticoagulants and antiplatelets generally safe for humans?

Anticoagulants like apixaban, rivaroxaban, and dabigatran are generally well tolerated, with apixaban showing lower risks of major bleeding compared to some other treatments. However, rivaroxaban may have a higher bleeding risk compared to other similar drugs. Antiplatelet agents like aspirin are also commonly used and generally considered safe, but they can increase bleeding risk. ^{1 4 6 7 8}

How do the drugs Rivaroxaban, Dabigatran, Apixaban, and Edoxaban differ from other treatments for blood clot prevention after heart procedures?

These drugs, known as direct oral anticoagulants (DOACs), are unique because they directly inhibit specific clotting factors in the blood, such as thrombin or Factor Xa, and do not require regular blood monitoring like older anticoagulants. They are also easier to use, as they can be taken orally and have predictable effects, making them a convenient option for preventing blood clots after heart procedures. ^{1 2 8 9 10}

What is the purpose of this trial?

The objective of the study is to compare short-term (8 weeks) anticoagulation therapy (DOAC) vs. antiplatelet therapy for the prevention of device thrombosis following transcatheter LAAC.

Eligibility Criteria

This trial is for adults over 18 who've had a successful transcatheter left atrial appendage closure (LAAC) to prevent strokes. It's not for those with anticoagulation therapy contraindications, past brain hemorrhages, issues with ultrasound heart scans (TEE), severe heart sac swelling or major bleeding post-LAAC, or women at childbearing age not on effective birth control.

Inclusion Criteria

Successful transcatheter LAAC with any approved device

Exclusion Criteria

I cannot take blood thinners due to severe side effects or conditions.

I have had several bleeding episodes in the last month.

I have not had major bleeding after my heart procedure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either anticoagulation therapy with DOAC or antiplatelet therapy for 60 days

8 weeks

Regular visits for monitoring and TEE evaluation

Follow-up

Participants are monitored for safety and effectiveness after treatment, including TEE evaluations

5 years

Annual visits for follow-up assessments

Treatment Details

Interventions

• Clopidogrel
• Low dose aspirin
• Rivaroxaban, dabigatran, apixaban, or edoxaban

Trial Overview The study compares two treatments after LAAC: short-term anticoagulants like Rivaroxaban and antiplatelet drugs such as low-dose aspirin and Clopidogrel. The goal is to see which better prevents blood clots without causing device thrombosis within the first 8 weeks.

Participant Groups

Group I: Anticoagulation therapy Active Control 1 Intervention

Direct oral anticoagulants (rivaroxaban, dabigatran, apixaban, or edoxaban; with dosage according to guideline recommendations) for 60 days.

Group II: Antiplatelet therapy Active Control 2 Interventions

Dual antiplatelet therapy with clopidogrel -75 mg/day- and low dose aspirin -80 to 125 mg/day for 60 days.

Rivaroxaban, dabigatran, apixaban, or edoxaban is already approved in European Union, United States for the following indications:

Approved in European Union as Rivaroxaban (Xarelto) for:

• Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation
• Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE)
• Prevention of recurrent DVT and PE

Approved in United States as Rivaroxaban (Xarelto) for:

• Reduction of risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation
• Treatment of DVT and PE
• Reduction in the risk of recurrence of DVT and PE

Approved in European Union as Dabigatran (Pradaxa) for:

• Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation
• Treatment of DVT and PE
• Prevention of recurrent DVT and PE

Approved in United States as Dabigatran (Pradaxa) for:

• Reduction of risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation
• Treatment of DVT and PE
• Reduction in the risk of recurrence of DVT and PE

Approved in European Union as Apixaban (Eliquis) for:

• Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation
• Treatment of DVT and PE
• Prevention of recurrent DVT and PE

Approved in United States as Apixaban (Eliquis) for:

• Reduction of risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation
• Treatment of DVT and PE
• Reduction in the risk of recurrence of DVT and PE

Approved in European Union as Edoxaban (Savaysa, Lixiana) for:

• Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation
• Treatment of DVT and PE
• Prevention of recurrent DVT and PE

Approved in United States as Edoxaban (Savaysa, Lixiana) for:

• Reduction of risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation
• Treatment of DVT and PE
• Reduction in the risk of recurrence of DVT and PE

Who Is Running the Clinical Trial?

Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Lead Sponsor

Trials

37

Recruited

9,700+

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]

Direct oral anticoagulants (DOACs) like dabigatran, rivaroxaban, apixaban, and edoxaban are widely used for anticoagulation due to their ease of use and lack of monitoring, making it crucial for physicians to manage them effectively during the perioperative period.

In managing DOACs, the decision to continue or discontinue the medication depends on the type of surgery; minor procedures may not require stopping the drug, while major surgeries may necessitate discontinuation hours before, based on the drug's pharmacokinetics and the patient's renal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative Management of Direct Oral Anticoagulants (DOACs): A Systemic Review. Sunkara, T., Ofori, E., Zarubin, V., et al.[2020]

Direct oral factor Xa-inhibitors like rivaroxaban and apixaban have been proven effective and safe in large clinical studies involving over 60,000 patients, making them reliable options for preventing and treating thrombosis.

These medications offer advantages over traditional treatments, such as no need for laboratory monitoring and convenient dosing, but they do have limitations, including reliance on kidney function and potential drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New anticoagulants - direct factor Xa-inhibitors]. Bächli, E.[2017]

Rivaroxaban is effective in preventing stroke and systemic embolism in patients with nonvalvular atrial fibrillation, showing superiority over warfarin and similar efficacy to other direct oral anticoagulants like dabigatran, apixaban, and edoxaban.

However, rivaroxaban may carry a higher risk of bleeding compared to other DOACs, which is an important consideration for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of rivaroxaban in the treatment of nonvalvular atrial fibrillation. Norby, FL., Alonso, A.[2022]

Novel anticoagulants like fondaparinux and NOACs (dabigatran, rivaroxaban, apixaban) offer advantages over traditional therapies by reducing the risk of complications such as heparin-induced thrombocytopenia and eliminating the need for routine monitoring, making them suitable for long-term use.

However, these new anticoagulants come with significant drawbacks, including the risk of drug accumulation in patients with kidney or liver disease, the absence of specific antidotes, and potential interactions with other medications, highlighting the need for careful management and further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[From heparin to apixaban: anticoagulants cut both ways?]. Hartung, K., Meyer, F., Bock, F., et al.[2018]

In a study involving 6,959 patients with venous thromboembolism (VTE), edoxaban, rivaroxaban, and apixaban showed no significant differences in preventing recurrent VTE, indicating similar effectiveness among these anticoagulants.

The safety profiles of the three drugs were also comparable, with no significant differences in the risk of serious bleeding events such as intracranial hemorrhage or gastrointestinal bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness and safety of edoxaban, rivaroxaban, and apixaban in patients with venous thromboembolism: A cohort study. Fukasawa, T., Seki, T., Nakashima, M., et al.[2023]

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 systematic review of 12 studies involving nearly 12,000 patients, all oral anticoagulants and antiplatelet agents significantly reduced the risk of recurrent venous thromboembolism compared to placebo, with vitamin K antagonists showing the highest risk reduction.

However, vitamin K antagonists also posed a greater risk of major bleeding compared to placebo, indicating a trade-off between efficacy and safety in their use for secondary prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety outcomes of oral anticoagulants and antiplatelet drugs in the secondary prevention of venous thromboembolism: systematic review and network meta-analysis. Castellucci, LA., Cameron, C., Le Gal, G., et al.[2022]

Rivaroxaban demonstrated better efficacy in preventing thrombosis after arthroplastic surgery, with only 4.89% of patients experiencing events compared to 9.55% in the control group.

Apixaban showed no significant difference in efficacy compared to enoxaparin, while enoxaparin had comparable or better safety outcomes, with fewer bleeding events (3.51%) compared to the control group (5.82%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of efficiency and safety of rivaroxaban, apixaban and enoxaparin for thromboprophylaxis after arthroplastic surgery: a meta-analysis. Yu, Z., Shan, P., Yang, X., et al.[2023]

Direct oral anticoagulants like rivaroxaban, dabigatran, and apixaban are effective for treating conditions such as deep venous thrombosis and preventing systemic embolism in non-valvular atrial fibrillation, making them convenient options for long-term use.

Despite their effectiveness, these anticoagulants carry a risk of bleeding complications, highlighting the need for specific management strategies in case such complications arise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of major bleeding complications in patients on long-term treatment with oral anticoagulants]. Pernod, G.[2014]

References

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

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

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

Perioperative Management of Direct Oral Anticoagulants (DOACs): A Systemic Review. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

[New anticoagulants - direct factor Xa-inhibitors]. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of rivaroxaban in the treatment of nonvalvular atrial fibrillation. [2022]

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

[From heparin to apixaban: anticoagulants cut both ways?]. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Comparative effectiveness and safety of edoxaban, rivaroxaban, and apixaban in patients with venous thromboembolism: A cohort study. [2023]

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

Apixaban: A Review in Venous Thromboembolism. [2020]

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

Efficacy and safety outcomes of oral anticoagulants and antiplatelet drugs in the secondary prevention of venous thromboembolism: systematic review and network meta-analysis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Comparison of efficiency and safety of rivaroxaban, apixaban and enoxaparin for thromboprophylaxis after arthroplastic surgery: a meta-analysis. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

[Management of major bleeding complications in patients on long-term treatment with oral anticoagulants]. [2014]