Antiplatelet Treatment Discontinuation After PFO Closure for Stroke

(HALTI Trial)

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

Trial Summary

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 data supports the effectiveness of antiplatelet treatment discontinuation after PFO closure for stroke?

Antiplatelet therapy is known to be effective in preventing strokes, as it reduces the risk of blood clots. However, stopping these drugs too soon can lead to a rebound effect, increasing the risk of new clots forming, as seen in other conditions like coronary artery disease. This suggests caution is needed when considering stopping antiplatelet treatment after PFO closure for stroke. ^{1 2 3 4 5}

Is it safe to stop antiplatelet treatment after PFO closure for stroke?

Stopping antiplatelet treatment can lead to serious risks, such as blood clots, especially if done abruptly. Studies show that stopping these medications can cause problems like heart attacks or strokes, so it's important to follow medical advice carefully. ^{1 2 6 7 8}

How does the treatment for PFO closure after stroke differ from other treatments?

The treatment involves discontinuing antiplatelet therapy after PFO (patent foramen ovale) closure, which is unique because it focuses on stopping medication rather than continuing it. This approach is different from standard treatments that typically involve ongoing antiplatelet therapy to prevent stroke recurrence, highlighting the potential risks and benefits of stopping these drugs. ^{1 2 4 5 9}

What is the purpose of this trial?

To determine the safety of antithrombotic treatment discontinuation 12 months following successful transcatheter PFO closure.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

References

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

Possibility of a rebound phenomenon following antiplatelet therapy withdrawal: a look at the clinical and pharmacological evidence. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

[Perioperative therapy with antiplatelet agents]. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Systematic review of the clinical impact of dual antiplatelet therapy discontinuation after acute coronary syndromes. [2018]

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

Antiplatelet therapy discontinuation after stent-assisted coil embolization for intracranial aneurysms: a single-center, long-term, retrospective, observational study. [2023]

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

Antiplatelet strategies for secondary prevention of stroke and TIA. [2021]

6. England 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. [2018]

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

Safety of short-term discontinuation of antiplatelet therapy in patients with drug-eluting stents. [2013]

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

Perioperative primary stroke: is aspirin cessation to blame? [2013]

9. Switzerland 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. [2020]