Anticoagulants vs Antiplatelets for Blood Clot Prevention After Heart Procedure

(ANDES Trial)

Not currently recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of two types of blood thinners in preventing blood clots after a heart procedure called LAAC. One group will take anticoagulants, such as rivaroxaban or dabigatran, while another group will use antiplatelet medications, like clopidogrel and aspirin, for 60 days. The researchers aim to determine which treatment better prevents clot formation. Individuals who have undergone a successful LAAC procedure and have no medical contraindications for blood thinners may be suitable for this trial. As a Phase 4 trial, this research involves FDA-approved treatments and seeks to understand their benefits for a broader patient population.

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 is the safety track record for these treatments?

Research has shown that direct oral anticoagulants (DOACs) such as rivaroxaban, dabigatran, apixaban, and edoxaban are generally safe for use. Some studies suggest that rivaroxaban might slightly increase stomach bleeding, but this is not considered a major concern. Overall, these medicines are as safe as other blood thinners used to prevent strokes in certain heart conditions.

For dual antiplatelet therapy, which includes clopidogrel and aspirin, studies suggest these are also well-tolerated. They are often used together to reduce the risk of heart attacks or strokes. Clopidogrel and aspirin have proven effective in maintaining heart health, especially when heart disease is present.

Both treatment options have already received approval for other uses, indicating they have passed safety checks. However, like all medications, they can have side effects. It is always important to consult a doctor about any concerns. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the anticoagulant treatments like rivaroxaban, dabigatran, apixaban, and edoxaban because they offer a potentially more effective alternative to the traditional dual antiplatelet therapy using clopidogrel and aspirin for preventing blood clots after heart procedures. Unlike standard antiplatelet treatments that prevent platelets from clumping together, these direct oral anticoagulants work by directly inhibiting specific proteins in the blood clotting process, potentially reducing the risk of clots more efficiently. This targeted action might lead to fewer side effects and better outcomes for patients recovering from heart procedures.

What evidence suggests that this trial's treatments could be effective for blood clot prevention after a heart procedure?

In this trial, participants will join one of two treatment arms to prevent blood clots after a heart procedure. One arm will receive anticoagulation therapy with direct oral anticoagulants (DOACs) such as rivaroxaban, dabigatran, apixaban, or edoxaban. Research has shown that these DOACs effectively prevent strokes in people with irregular heartbeats and are as safe and effective as older treatments like warfarin for stopping blood clots.

The other arm will receive dual antiplatelet therapy, combining clopidogrel and low-dose aspirin to prevent heart problems by stopping tiny blood cells called platelets from sticking together and forming clots. Some studies have suggested that this combination might not be more effective than aspirin alone for preventing deaths related to heart issues. Each treatment offers benefits, and the choice often depends on the specific condition and patient needs. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6206466/

Direct Oral Anticoagulants: A Quick Guide - PMC DOACs have been found to be at least as safe and effective as vitamin K antagonists in randomised, controlled trials for stroke prevention in AF.

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK557502/

Rivaroxaban - StatPearls - NCBI Bookshelf In 2011 the FDA approved its use in primary and secondary stroke prevention in people with cardiac arrhythmia, most commonly in nonvalvular Atrial fibrillation.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1538783622021092

Comparative effectiveness and safety of edoxaban ... In routine care, edoxaban, rivaroxaban, and apixaban appear to have similar effectiveness and safety in the treatment of VTE.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1207541

Apixaban for Extended Treatment of Venous ... At a dose of 5 mg twice daily, apixaban has been shown to be effective for the prevention of stroke in patients with atrial fibrillation, and at a dose of 2.5 ...

5. xareltohcp.com xareltohcp.com/dvt-prophylaxis/

DVT Prophylaxis | XARELTO® (rivaroxaban) HCP There are limited data on the relative effectiveness of XARELTO® and warfarin in reducing the risk of stroke and systemic embolism when warfarin therapy is well ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK519025/

Anticoagulation Safety - StatPearls - NCBI Bookshelf - NIH Studies reveal that rivaroxaban has a slightly higher rate of gastrointestinal bleeding. However, the results are not statistically significant.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0741521416003190

Quick reference guide to the new oral anticoagulants Rivaroxaban for the prevention of venous thromboembolism in elective hip or knee surgery (10 mg OD for 35/12 days, respectively), stroke prevention in patients ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/rivaroxaban-oral-route/description/drg-20075013

Rivaroxaban (oral route) - Side effects & dosage Rivaroxaban is used to treat and prevent deep venous thrombosis (DVT), a condition in which harmful blood clots form in the blood vessels of the legs.