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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well the drug Warfarin treats clots in artificial heart valves. Researchers aim to determine if Warfarin helps clear these clots and maintains proper valve function. Ideal candidates for this trial have an artificial aortic valve (made from animal tissue or synthetic materials) and have had it for at least 48 hours. Participants will undergo imaging tests to assess valve health before and after using Warfarin for three months. As an unphased trial, this study offers participants the chance to contribute to valuable research that could enhance treatment for others with artificial heart valves.

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 prior data suggests that Warfarin is safe for treating prosthetic heart valve clots?

Research has shown that warfarin is often used as a blood thinner after receiving a new aortic valve. The American College of Cardiology recommends its use for about three months to help prevent blood clots on the valve.

One study found that 83% of patients responded well to warfarin, indicating its effectiveness for many in managing clots. However, regular blood tests are necessary to ensure safe use. Some individuals might experience side effects like bleeding, a known risk with blood thinners.

Overall, warfarin remains a well-researched and commonly used treatment for blood clots related to valve replacements, particularly in individuals with artificial valves. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Warfarin for prosthetic heart valve clots because it offers a targeted approach to tackling thrombus formation on bioprosthetic valves. Unlike other treatments that might not specifically focus on this issue, Warfarin acts as an anticoagulant, aiming to dissolve existing clots and prevent new ones from forming. This treatment is particularly promising as it uses Vitamin K antagonism to achieve a precise INR (International Normalized Ratio) range of 2-3, potentially ensuring effective and consistent anticoagulation. This specific targeting could lead to clearer improvements in valve function and patient outcomes compared to broader anticoagulation strategies.

What evidence suggests that Warfarin might be an effective treatment for prosthetic heart valve clots?

Studies have shown that warfarin effectively treats blood clots on bioprosthetic heart valves. Research indicates that warfarin breaks down these clots, preventing further complications. One study found that warfarin outperformed some other blood thinners in stopping blood clots or related issues. In this trial, participants with prosthetic valve abnormalities suggestive of thrombus will receive anticoagulation therapy with warfarin. Warfarin remains the best option for managing clots in heart valve patients, as no alternative has proven more effective. This makes it a reliable choice for those with prosthetic heart valve clots. ^{2 3 6 7 8}

Who Is on the Research Team?

Raj Makkar

Principal Investigator

Cedars-Sinai Medical Center, Los Angeles, California

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1936879816320787

Outcomes of Warfarin Therapy for Bioprosthetic Valve ... The aim of this study was to assess the efficacy of warfarin in the treatment of bioprosthetic valve thrombosis (BPVT) of surgically implanted valves.

2. jacc.org jacc.org/doi/10.1016/j.jcin.2016.11.027

Outcomes of Warfarin Therapy for Bioprosthetic Valve ... The aim of this study was to assess the efficacy of warfarin in the treatment of bioprosthetic valve thrombosis (BPVT) of surgically implanted valves.

3. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2300067

Apixaban or Warfarin in Patients with an On-X Mechanical ... Apixaban did not demonstrate noninferiority to warfarin and is less effective than warfarin for the prevention of valve thrombosis or thromboembolism.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9409674/

Bioprosthetic Aortic Valve Thrombosis and Literature Review ... effective as warfarin [7], but data are lacking for late thrombosis. DAPT was found by many studies to be suboptimal for both the prevention ...

5. jtcvs.org jtcvs.org/article/S0022-5223(24)00610-X/fulltext

There is still no alternative to warfarin for mechanical valves The primary efficacy outcome (death, thromboembolic events, and intracardiac thrombus) occurred in 3.7% of the warfarin group and in no ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5124764/

Safety and Use of Anticoagulation After Aortic Valve ... The American College of Cardiology guidelines recommend 3 months of anticoagulation after replacement of the aortic valve with a bioprosthesis.

7. jacc.org jacc.org/doi/10.1016/j.jacc.2019.12.037

Long-Term Outcomes of Anticoagulation for Bioprosthetic ... A total of 83 patients treated with warfarin for suspected BPVT (age 57 ± 18 years; 45 men [54%]) were matched to 166 control subjects; ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9163724/

DOACs in Mechanical and Bioprosthetic Heart Valves There has been an uptrend in the usage of direct-acting oral anticoagulants (DOACs) in both mechanical and bioprosthetic heart valves.