Antiplatelet Treatment Discontinuation After PFO Closure for Stroke

(HALTI Trial)

Recruiting at 1 trial location

Overseen By Josep Rodes-Cabau

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Josep Rodes-Cabau

Disqualifiers: Age >60, Diabetes, Atrial fibrillation, others

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

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

Compensation: Varies

Number of Visits: 36

Duration: 12 months

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety of discontinuing antiplatelet medication (which prevents blood clots) one year after closing a hole in the heart (PFO) for individuals who experienced a stroke with no known cause. Participants will stop their medication 12 months post-procedure and undergo a check-up and brain scan before and after discontinuation. The trial seeks individuals aged 60 or younger who have had this type of stroke and successfully closed the heart hole with a device. Those with conditions like diabetes or certain clotting problems are not suitable for this trial. As an unphased trial, it offers participants the chance to contribute to important research that could enhance future treatment guidelines.

Will I have to stop taking my current medications?

The trial is studying whether it's safe to stop antithrombotic treatment (medication that prevents blood clots) 12 months after a PFO closure. It doesn't specify if you need to stop other medications, so it's best to ask the trial team for guidance.

What prior data suggests that antiplatelet treatment discontinuation is safe after PFO closure?

Research has shown that stopping antiplatelet medication after closing a Patent Foramen Ovale (PFO) might be safe for some individuals. Studies have found that even with short-term use of antithrombotic medication, such as six months, the risk of another stroke remains low—about 0.3% per year.

One study discovered that after PFO closure, the chance of serious bleeding is very low, occurring in just 2% of patients over more than ten years. However, some complications arose during the procedure, with a small number of patients experiencing atrial fibrillation, an irregular heartbeat.

Overall, these findings suggest that many individuals might safely discontinue antiplatelet medication after PFO closure. However, individual risks can vary, so consulting a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the antiplatelet treatment discontinuation after PFO closure for stroke because it challenges the current standard, which typically involves long-term antiplatelet therapy. This trial investigates whether stopping antiplatelet drugs 12 months after a PFO closure can maintain stroke prevention without the risks associated with prolonged medication use, such as bleeding. If successful, this approach could simplify patient care and reduce medication-related side effects, offering a more streamlined and potentially safer management option for patients who have undergone PFO closure.

What evidence suggests that antiplatelet treatment discontinuation might be an effective approach after PFO closure for stroke?

This trial will evaluate the effects of discontinuing antiplatelet treatment after PFO closure for stroke prevention. Research has shown that stopping medication to prevent blood clots after closing a small hole in the heart (called a PFO) might not increase stroke risk. One study found that taking blood clot prevention medicine for just six months after closing the PFO kept stroke rates very low, at only 0.3% per year. This suggests that not everyone needs to continue these medications long-term. Another study found that closing the PFO reduced stroke risk more than medication alone. These findings suggest that stopping the medication after a successful PFO closure could be a safe and effective way to prevent strokes. Participants in this trial will discontinue antiplatelet treatment 12 months post-PFO closure to further investigate these findings. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals under 60 who've had a cryptogenic stroke or TIA and successfully underwent transcatheter PFO closure. It's not for those over 60, with MRI contraindications, high RoPE score, significant residual shunt post-closure, atrial fibrillation after closure, multiple cardiovascular risk factors including smoking and hypertension, diabetes, thrombophilia or recurrent strokes/TIAs within a year of closure.

Inclusion Criteria

You have already had a successful closure of a hole in your heart using a special device.

I am 60 or younger and had a stroke/TIA treated by closing a hole in my heart.

Exclusion Criteria

I had a stroke or mini-stroke within a year after my PFO closure.

I have diabetes.

I have a blood clotting disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive antiplatelet treatment following PFO closure

12 months

Clinical evaluation and cerebral MRI at 12 months

Follow-up

Participants are monitored for new ischemic lesions and bleeding events

24 months

Clinical evaluation and cerebral MRI at 24 months

Long-term follow-up

Participants are monitored for bleeding and ischemic events

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Antiplatelet treatment discontinuation

Trial Overview The study tests the safety of stopping antiplatelet treatment one year after successful PFO (a hole in the heart) closure in young patients who have had an unexplained stroke. The goal is to see if it's safe to discontinue blood-thinning medications that prevent clotting after this procedure.

How Is the Trial Designed?

Group I: Antiplatelet treatment discontinuation Experimental Treatment 1 Intervention

At 12 months post-PFO closure, patients will discontinue the antiplatelet treatment. All patients will undergo a clinical evaluation and cerebral MRI at 12 months (before antiplatelet treatment cessation) and at 24 months post-PFO closure.

Who Is Running the Clinical Trial?

Josep Rodes-Cabau

Lead Sponsor

Trials

4

Recruited

1,400+

Published Research Related to This Trial

Short-term discontinuation of thienopyridine (an antiplatelet medication) is relatively safe for patients with drug-eluting stents, especially if acetylsalicylic acid (another antiplatelet) is continued, as only 6% of patients experienced late stent thrombosis within 10 days in this scenario.

In contrast, stopping both antiplatelet medications simultaneously significantly increases the risk of late stent thrombosis, with 75% of events occurring within 10 days after discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of short-term discontinuation of antiplatelet therapy in patients with drug-eluting stents. Eisenberg, MJ., Richard, PR., Libersan, D., et al.[2013]

Discontinuing clopidogrel therapy after hospitalization for acute coronary syndrome significantly increases the risk of adverse outcomes, such as death or recurrent ACS, particularly within the first 90 days after stopping the medication.

Patients who had been on clopidogrel for 90 days or less faced even higher risks of adverse outcomes compared to those who had been treated for longer, highlighting the importance of maintaining therapy in the early post-discharge period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of death and recurring acute coronary syndrome after stopping clopidogrel therapy in a large commercially-insured population in the US. Stephenson, JJ., Chang, CL., Devecchis Wygant, G., et al.[2018]

Antiplatelet therapy is crucial for preventing blood clots in patients with artherothrombotic disease, but it poses a risk of bleeding during surgery, requiring careful management of when to stop the medication.

Prematurely stopping antiplatelet therapy can lead to serious thromboembolic events, particularly in patients with intracoronary stents, highlighting the importance of maintaining therapy until the stent is fully healed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Perioperative therapy with antiplatelet agents]. Lepper, W., Kelm, M.[2018]

Discontinuing dual antiplatelet therapy after acute coronary syndromes is commonly based on physician decisions, and longer durations of this therapy are associated with lower risks of all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and stent thrombosis, according to a review of 29 studies.

The review highlights the need for further research to determine the optimal duration of dual antiplatelet therapy, as the benefits observed were not consistent across all studies, particularly in randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of the clinical impact of dual antiplatelet therapy discontinuation after acute coronary syndromes. Zeymer, U., Becher, A., Jennings, E., et al.[2018]

In a study of 240 patients who underwent stent-assisted coil embolization (SACE) for intracranial aneurysms, it was found safe to discontinue single antiplatelet therapy (SAPT) after 2 years if patients showed no ischemic complications and stable intraaneurysmal signals on MRA.

The study identified that the type of stent used (T- or Y-stent) was a significant risk factor for delayed ischemic complications, suggesting that careful consideration is needed when deciding to reduce or stop antiplatelet therapy in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiplatelet therapy discontinuation after stent-assisted coil embolization for intracranial aneurysms: a single-center, long-term, retrospective, observational study. Goto, S., Izumi, T., Nishihori, M., et al.[2023]

Regular use of antiplatelet drugs, like aspirin and clopidogrel, is crucial for patients with coronary artery disease, as they significantly lower the risk of death, but abrupt discontinuation can lead to serious complications.

Discontinuing these medications can trigger acute thrombotic events after a delay of 8-25 days, suggesting a rebound effect that increases the risk of ischemic vascular disease, highlighting the need to adhere to current guidelines against premature withdrawal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possibility of a rebound phenomenon following antiplatelet therapy withdrawal: a look at the clinical and pharmacological evidence. Lordkipanidzé, M., Diodati, JG., Pharand, C.[2018]

Antiplatelet therapy is proven to be effective for preventing secondary strokes, which are responsible for about 25% of all stroke events, highlighting its importance in managing high-risk patients.

Current standard treatments include aspirin, clopidogrel, and a combination of aspirin with extended-release dipyridamole, but ongoing research is exploring new agents and combinations to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiplatelet strategies for secondary prevention of stroke and TIA. Ishida, K., Messé, SR.[2021]

A case study was presented where a patient experienced a thrombotic event after stopping aspirin, which was used for primary prevention, following dermatologic surgery.

The authors concluded that while this case raises concerns, the overall evidence does not strongly support that stopping aspirin directly causes thrombotic events, especially considering the high baseline risk in patients undergoing Mohs surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative primary stroke: is aspirin cessation to blame? Kimyai-Asadi, A., Jih, MH., Goldberg, LH.[2013]

Individualized antiplatelet therapy based on platelet function analysis (PFA) did not show a significant reduction in recurrent strokes or bleeding risks compared to standard antiplatelet therapy in a review of two observational studies involving 1136 patients.

The studies revealed conflicting results regarding the effectiveness of PFA-guided therapy for aspirin non-responders, indicating a need for larger randomized controlled trials to better understand the potential benefits and confounding factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Platelet Function Analysis-Guided Aspirin and/or Clopidogrel Therapy in Preventing Secondary Stroke: A Systematic Review and Meta-Analysis. Yan, AR., Naunton, M., Peterson, GM., et al.[2020]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1707404

Patent Foramen Ovale Closure or Antiplatelet Therapy for ... Serious adverse events occurred in 23.1% of the patients in the PFO closure group and in 27.8% of the patients in the antiplatelet-only group (P ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9633204/

Antithrombotic Therapy Duration after Patent Foramen Ovale ... Short-term (6 months) ATT after PFO closure did not impair the clinical outcome, with a preserved low rate of recurrent stroke (0.3% patient-year) and device ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04475510

Discontinuation of Antithrombotic Treatment Following ... All patients will undergo a clinical evaluation and cerebral MRI at 12 months (before antiplatelet treatment cessation) and at 24 months post-PFO closure.

4. ahajournals.org ahajournals.org/doi/10.1161/jaha.117.007146

Patent Foramen Ovale Closure for Stroke Prevention and ... The intention‐to‐treat analysis now demonstrated a significant reduction in recurrent ischemic strokes in the PFO closure arm (HR, 0.55; 95% CI, 0.305–1.0; P= ...

5. j-saudi-heart.com j-saudi-heart.com/cgi/viewcontent.cgi?article=1427&context=jsha

Comparison of Patent Foramen Ovale Closure vs Medical ... Patients who underwent PFO closure had a reduced incidence of cryptogenic stroke and TIA but demonstrated a higher rate of AF compared to those ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04475510

Discontinuation of Antithrombotic Treatment Following ... All patients will undergo a clinical evaluation and cerebral MRI at 12 months (before antiplatelet treatment cessation) and at 24 months post-PFO closure.

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1705915

Patent Foramen Ovale Closure or Anticoagulation vs. ... Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group ...

8. academic.oup.com academic.oup.com/eurjpc/article/31/Supplement_1/zwae175.188/7692466

Safety and efficacy of antiplatelet cessation after transcatheter ... The aim of our analysis is to explore the safety and efficacy of antiplatelet cessation after transcatheter patent foramen ovale closure.

9. jacc.org jacc.org/doi/10.1016/j.jacc.2018.10.061

Long-Term Follow-Up After Closure of Patent Foramen ... PFO closure was associated with a low rate of ischemic events (stroke, 1%) at >10 years of follow-up. Major bleeding events occurred in 2% of ...