Warfarin for Prosthetic Heart Valve Clots

(RESOLVE Trial)

Overseen By Tarun Chakravarty, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Cedars-Sinai Medical Center

Must be taking: Anticoagulants

Disqualifiers: Renal insufficiency, Iodine allergy

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

3000 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

What data supports the effectiveness of the drug Warfarin for prosthetic heart valve clots?

Warfarin is a widely recommended anticoagulant (blood thinner) for patients with mechanical heart valves, as it helps prevent blood clots that can lead to serious complications. It is considered effective when managed properly, although it requires careful monitoring to maintain the right dosage and avoid side effects. ^{1 2 3 4 5}

Is warfarin safe for humans?

Warfarin is generally considered safe for humans when used as prescribed, but its effects can vary due to individual differences, and it requires careful management to avoid complications like bleeding. It is commonly used for patients with mechanical heart valves, but monitoring and adjustments may be needed to maintain safety. ^{2 3 6 7 8}

How does the drug Warfarin differ from other treatments for prosthetic heart valve clots?

Warfarin is unique because it is a vitamin K antagonist (VKA) that requires careful monitoring of the international normalized ratio (INR) to ensure effective prevention of clots in patients with mechanical heart valves. Unlike newer anticoagulants, Warfarin has a well-established role in this condition, but it can be challenging due to issues like warfarin resistance, which may require switching to another VKA like acenocoumarol. ^{2 4 5 9 10}

What is the purpose of this trial?

This is a prospective study designed to evaluate the structural and functional integrity of transcatheter or surgical bioprosthetic valves with multimodality imaging. The study further aims to confirm resolution of the early bioprosthetic valve thrombotic changes with anticoagulation.

Research Team

Raj Makkar

Principal Investigator

Cedars-Sinai Medical Center, Los Angeles, California

Eligibility Criteria

This trial is for adults over 18 who have had a bioprosthetic aortic valve placed at least two days before joining. They must be able to give informed consent and follow the study's procedures. People with kidney issues (creatinine > 1.5 mg/dL) or allergies to iodinated contrast agents cannot participate.

Inclusion Criteria

Ability to provide informed consent and follow-up with protocol procedures.

I had a heart valve replacement at least 2 days ago.

Exclusion Criteria

My kidney function is impaired with creatinine levels above 1.5 mg/dL.

You are allergic to iodine-based contrast agents.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Imaging

Patients undergo cardiac contrast CT imaging and transthoracic echocardiography to evaluate structural and functional integrity of the aortic valves

1 week

1 visit (in-person)

Treatment

Patients with prosthetic valve abnormalities suggestive of thrombus are administered anticoagulation therapy with Vitamin K antagonists (Warfarin) for 3 months

12 weeks

Regular monitoring visits

Follow-up Imaging

Repeat contrast CT of the chest and transthoracic imaging to evaluate the response to anticoagulation therapy

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Warfarin

Trial Overview The study is testing how well Warfarin, an anticoagulant medication, can resolve blood clots on artificial heart valves. It involves detailed imaging to check the valves' condition before and after treatment.

Participant Groups

Group I: Pre-existing bioprosthetic aortic valve Experimental Treatment 1 Intervention

Patients with a history of surgical or transcatheter valve replacement with bioprosthetic valves undergo cardiac contrast CT imaging and transthoracic echocardiography to evaluate structural and functional integrity of the aortic valves. Patients with prosthetic valve abnormalities suggestive of thrombus will be administered anticoagulation therapy with Vitamin K antagonists (Warfarin) for 3 months with goal INR 2-3, followed by repeat contrast CT of the chest and transthoracic imaging. Repeat imaging following 3 months of anticoagulation therapy is performed to evaluate the response to anticoagulation therapy.

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

Approved in United States as Warfarin for:

• Prophylaxis and treatment of thromboembolic complications from atrial fibrillation or cardiac valve replacement
• Reduction in the risk of death, recurrent myocardial infarction, and thromboembolic events after myocardial infarction

Approved in European Union as Warfarin for:

• Prevention of thromboembolic events in patients with atrial fibrillation
• Treatment of deep vein thrombosis and pulmonary embolism
• Prevention of recurrent myocardial infarction

Approved in Canada as Warfarin for:

• Prophylaxis and treatment of thromboembolic complications from atrial fibrillation or cardiac valve replacement
• Reduction in the risk of death, recurrent myocardial infarction, and thromboembolic events after myocardial infarction

Who Is Running the Clinical Trial?

Cedars-Sinai Medical Center

Lead Sponsor

Trials

523

Recruited

165,000+

Findings from Research

A case of acute aortic mechanical valve thrombosis occurred six months after surgery due to the patient discontinuing anticoagulation therapy, highlighting the importance of consistent anticoagulant management to prevent serious complications.

The patient was successfully treated with intravenous thrombolysis, which resolved the thrombosis and improved symptoms, suggesting that timely intervention is critical; additionally, a bridging protocol with heparin is recommended when starting warfarin to avoid procoagulant effects during the initial days of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute mechanical prosthetic valve thrombosis after initiating oral anticoagulation therapy. Is bridging anticoagulation with heparin required? Charokopos, N., Antonitsis, P., Artemiou, P., et al.[2018]

A 65-year-old male patient with a mechanical prosthetic aortic valve experienced warfarin resistance, where increasing doses of warfarin did not raise his INR levels adequately for effective thromboembolism prevention.

Switching from warfarin to acenocoumarol successfully stabilized the patient's INR over a year, suggesting that acenocoumarol may be a viable alternative for patients with warfarin resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Warfarin resistance: possibilities to solve this problem. A case report. Mostbauer, H., Nishkumay, O., Rokyta, O., et al.[2022]

Heart valve replacement is a safe and effective treatment for severe valvular heart disease, significantly improving patients' hemodynamics, but it necessitates lifelong anticoagulant therapy.

The use of portable coagulometers and the Internet for managing warfarin therapy after heart valve replacement presents promising opportunities to enhance patient compliance and reduce complications, although their safety and affordability need further evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining portable coagulometers with the Internet: A new model of warfarin anticoagulation in patients following mechanical heart valve replacement. Huang, Y., Huang, L., Han, Z.[2022]

Low-molecular-weight heparin has been reported as a treatment option for patients with prosthetic heart valves, but there are significant risks associated with its use, as demonstrated by two cases of treatment failure leading to thrombosis.

Both patients experienced severe clinical complications due to thrombosed prosthetic heart valves, ultimately requiring successful valve replacement surgeries, highlighting the need for careful management in anticoagulation therapy for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-molecular-weight heparin for prosthetic heart valves: treatment failure. Lev-Ran, O., Kramer, A., Gurevitch, J., et al.[2019]

Patients with mechanical valve prostheses benefit from a combination of Warfarin and low-dose aspirin, which effectively reduces the risk of valve thrombosis and systemic embolism while maintaining a low risk of bleeding.

Managing anticoagulant therapy in pregnant women with prosthetic heart valves is particularly challenging, as traditional oral anticoagulants like Warfarin can harm the fetus, and heparin options have shown limited effectiveness in preventing thromboembolic complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antithrombotic therapy in patients with prosthetic heart valves. Mohamed, H.[2021]

In a study of 64 children and young adults with mechanical heart valves, both Coumadin (warfarin) and a combination of aspirin plus dipyridamole were found to provide similar protection against clotting complications, with no significant differences in survival or thromboembolism rates.

While bleeding events were more frequent in the Coumadin group, this difference was not statistically significant, suggesting that both treatment options are relatively safe and effective for preventing complications in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticoagulation in children with mechanical valve prostheses. Bradley, SM., Sade, RM., Crawford, FA., et al.[2022]

In a study of 220 patients undergoing surgical bioprosthetic valve implantation or repair, edoxaban was found to be noninferior to warfarin in preventing thromboembolic events, with only 3.7% of warfarin patients experiencing these events compared to none in the edoxaban group.

The safety profile showed that major bleeding occurred in 0.9% of warfarin patients and 2.8% of edoxaban patients, suggesting that edoxaban may have a comparable risk of major bleeding during the first 3 months post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of edoxaban in patients early after surgical bioprosthetic valve implantation or valve repair: A randomized clinical trial. Shim, CY., Seo, J., Kim, YJ., et al.[2022]

In a study of 54 patients who received apixaban after bioprosthetic valve replacement, the medication was found to be safe and well-tolerated, with a low incidence of major (2%) and minor (6%) bleeding events.

The study reported a 33% rate of all-cause readmission or emergency visits and a 6% mortality rate within 3 months, indicating that while apixaban is generally safe, further research is needed to fully understand its efficacy, especially in patients with mitral valve replacements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Apixaban Following Bioprosthetic Valve Replacements: A Retrospective Evaluation. Ball, K., Covington, EW.[2022]

A 58-year-old man with a mechanical aortic valve experienced severe symptoms due to prosthetic valve thrombosis, but was successfully treated solely with anticoagulation therapy (warfarin) instead of surgery, which was deemed too risky.

After six months of continued warfarin therapy and close monitoring, the patient's symptoms improved significantly, with echocardiography showing complete dissolution of the thrombus and a return to normal valve function, demonstrating the efficacy of anticoagulation in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanical Aortic Valve Thrombosis with Heart Failure Successfully Treated with Oral Anticoagulation: A Case Report. Ababneh, M., Al-Kasasbeh, A., Algorani, E.[2023]

Mechanical prosthetic valves require lifelong anticoagulant therapy to reduce the risk of blood clots, with the intensity of treatment tailored based on individual risk factors and valve characteristics.

Recent guidelines support the use of low molecular weight heparins for patients with prosthetic valves, despite their current lack of official authorization, due to their ease of use and stable action, while also highlighting the need for careful monitoring to manage the risk of bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Anticoagulation of valvular prostheses]. Hanania, G., Maroni, JP., el Hajj, Y.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Acute mechanical prosthetic valve thrombosis after initiating oral anticoagulation therapy. Is bridging anticoagulation with heparin required? [2018]

2. England pubmed.ncbi.nlm.nih.gov

Warfarin resistance: possibilities to solve this problem. A case report. [2022]

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

Combining portable coagulometers with the Internet: A new model of warfarin anticoagulation in patients following mechanical heart valve replacement. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Low-molecular-weight heparin for prosthetic heart valves: treatment failure. [2019]

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

Antithrombotic therapy in patients with prosthetic heart valves. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Anticoagulation in children with mechanical valve prostheses. [2022]

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

Efficacy and safety of edoxaban in patients early after surgical bioprosthetic valve implantation or valve repair: A randomized clinical trial. [2022]

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

Safety and Efficacy of Apixaban Following Bioprosthetic Valve Replacements: A Retrospective Evaluation. [2022]

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

Mechanical Aortic Valve Thrombosis with Heart Failure Successfully Treated with Oral Anticoagulation: A Case Report. [2023]

10. France pubmed.ncbi.nlm.nih.gov

[Anticoagulation of valvular prostheses]. [2019]