Antiplatelet Therapy for Coronary Heart Disease

(SWAP-9 Trial)

Overseen By Andrea Burton, MPH, CCRP

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Florida

Must be taking: Dual antiplatelet therapy

Must not be taking: Oral anticoagulants, Heparin

Disqualifiers: Stent thrombosis, Hemodynamic instability, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how different strategies for reducing antiplatelet therapy affect individuals with a heart stent. It compares the effectiveness of using genetic information (ABCD-GENE) to guide treatment changes versus not using it. Individuals who have had a stent placed for heart disease and are taking medications like aspirin (an antiplatelet drug) and clopidogrel may qualify if their procedure occurred more than a month ago. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, allowing researchers to understand its benefits for a broader range of patients.

Will I have to stop taking my current medications?

The trial requires participants to be on dual antiplatelet therapy (DAPT) with low-dose aspirin and either prasugrel or ticagrelor. If you are already on these medications, you will not need to stop them. However, if you are taking any oral anticoagulants or certain other medications, you may not be eligible to participate.

What is the safety track record for these treatments?

Research shows that both prasugrel and ticagrelor, the medications used in this study, have been tested for their effects and safety in people with heart conditions.

Studies have found that prasugrel can reduce the risk of heart attacks but may increase the chance of serious bleeding. For instance, one study showed that prasugrel led to fewer heart problems but had a higher risk of bleeding compared to clopidogrel.

Ticagrelor has also been researched and generally shows a lower risk of death from heart issues compared to clopidogrel. However, it can also raise the risk of major bleeding. In one study, ticagrelor had a similar rate of major bleeding as another treatment.

Both prasugrel and ticagrelor are approved for use in certain heart conditions, indicating they are generally safe, though some risks, especially related to bleeding, exist. Participants in the trial should consider these factors when deciding whether to join. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they explore a new approach to managing coronary heart disease through ABCD-GENE-guided de-escalation. Unlike the standard of care that typically involves fixed doses of antiplatelet medications like aspirin and clopidogrel, this method uses genetic information to tailor treatment. For patients with an ABCD-GENE score of 10 or higher, stronger medications like prasugrel or ticagrelor are used, potentially improving outcomes by optimizing therapy based on individual genetic profiles. This personalized strategy could lead to more effective prevention of blood clots while minimizing side effects, making it a promising avenue for future heart disease management.

What evidence suggests that this trial's treatments could be effective for coronary heart disease?

In this trial, participants will receive different antiplatelet therapies to manage coronary heart disease. Research has shown that prasugrel, one of the treatments in this trial, reduces serious heart problems like stent blockage more effectively than clopidogrel, though it may increase the risk of bleeding. Real-world evidence suggests prasugrel often outperforms ticagrelor, another treatment option in this trial, for individuals with sudden heart issues. However, ticagrelor has been associated with a slightly higher rate of non-fatal heart attacks compared to prasugrel. Despite this, ticagrelor can still help prevent heart attacks and other heart problems. Both medications have undergone extensive study and are proven effective in managing heart disease after stent placement. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with coronary heart disease who have undergone a procedure to open their heart's arteries, known as PCI. Participants should be currently on dual antiplatelet therapy but cannot join if they have conditions that the study doesn't allow.

Inclusion Criteria

Provide written informed consent

I had a stent placed in my heart and take specific heart medications daily.

Exclusion Criteria

Prior history of stent thrombosis

I had a heart procedure within the last 30 days.

My blood pressure and heart rate are stable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo dual antiplatelet therapy (DAPT) with either ABCD-GENE-guided or unguided de-escalation strategies following PCI

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including measurement of P2Y12 Reaction Units (PRU) at 30±5 days

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aspirin
• Clopidogrel
• Prasugrel
• Ticagrelor

Trial Overview The SWAP-9 Study is testing whether it's better to choose post-PCI medication based on genetic information (ABCD-GENE guided) or not. It compares staying on standard drugs (aspirin and clopidogrel) versus switching to either Prasugrel or Ticagrelor alone.

How Is the Trial Designed?

Group I: ABCD-GENE-guided de-escalation Experimental Treatment 1 Intervention

ABCD-GENE ≥10: prasugrel 10 mg qd or ticagrelor 90 mg od monotherapy. ABCD-GENE \<10: Aspirin 81 mg qd and clopidogrel 75 mg qd.

Group II: Unguided de-escalation Active Control 1 Intervention

Aspirin 81 mg qd and clopidogrel 75 mg qd.

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

Approved in European Union as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in United States as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in Canada as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in China as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Published Research Related to This Trial

Ticagrelor is a new type of P2Y(12) antagonist that works differently from traditional antiplatelet medications like clopidogrel and prasugrel, providing a potentially more effective option for treating acute coronary syndromes.

Clinical trials have shown that ticagrelor, when used with aspirin, has a favorable safety profile and can overcome some limitations associated with clopidogrel, making it a valuable addition to antiplatelet therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor: a P2Y12 antagonist for use in acute coronary syndromes. Wijeyeratne, YD., Joshi, R., Heptinstall, S.[2022]

Antiplatelet therapy, particularly the combination of clopidogrel and aspirin, is the standard treatment for patients undergoing procedures like percutaneous coronary intervention and those with acute coronary syndromes to reduce cardiovascular events.

Despite the effectiveness of clopidogrel, there are significant limitations in its use, as some patients may still experience atherothrombotic events, highlighting the need for improved antiplatelet strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current antiplatelet therapies: benefits and limitations. Angiolillo, DJ., Guzman, LA., Bass, TA.[2018]

Ticagrelor (Brilinta™) was approved by the FDA for treating acute coronary syndromes based on the PLATO trial, which involved 18,624 patients and compared its efficacy to clopidogrel over 6-12 months.

Despite its approval, there were significant concerns from FDA reviewers regarding its efficacy and safety, particularly related to bleeding risks and the potential reduction in effectiveness when used with high doses of aspirin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor FDA approval issues revisited. Serebruany, VL.[2018]

Dual antiplatelet therapy (DAPT), which includes aspirin and a P2Y12 inhibitor, remains the standard treatment for patients undergoing percutaneous coronary interventions (PCI) to reduce thrombotic events.

Recent randomized controlled trials have focused on finding less aggressive antithrombotic regimens that balance the risks of ischemic events and bleeding, leading to updates in clinical practice guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiplatelet therapy in percutaneous coronary intervention: latest evidence from randomized controlled trials. Galli, M., Angiolillo, DJ.[2023]

Ticagrelor (Brilinta) has been approved by the FDA as an oral antiplatelet medication to be used with low-dose aspirin for reducing thrombotic cardiovascular events in patients with acute coronary syndrome (ACS).

Ticagrelor will compete with existing medications like clopidogrel (Plavix) and prasugrel (Effient), especially as clopidogrel is expected to become available as a generic option soon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor (Brilinta)--better than clopidogrel (Plavix)? [2018]

In a study of 249,907 patients with acute coronary syndrome (ACS), early initiation of dual anti-platelet therapy was associated with better outcomes, while triple therapy (thienopyridines + aspirin + glycoprotein IIb/IIIa receptor inhibitors) showed improved results compared to dual therapy in some cases.

Patients receiving glycoprotein IIb/IIIa receptor inhibitors had higher rates of major bleeding and mortality, indicating that while triple therapy can be beneficial, it also carries significant risks that need to be carefully managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes, health resource use, and cost in patients with early versus late dual or triple anti-platelet treatment for acute coronary syndrome. Friedman, H., Mollon, P., Lian, J., et al.[2018]

New antiplatelet agents like Prasugrel and Ticagrelor have been approved for treating acute coronary syndromes (ACS) in Europe, offering faster and more consistent platelet inhibition compared to traditional agents like aspirin and clopidogrel.

However, these newer medications also carry an increased risk of bleeding in certain patient groups, highlighting the need for personalized treatment plans that consider individual patient characteristics and risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Platelet inhibitors in clinical practice]. Gebhard, C., Beer, J.[2018]

In the CURRENT-OASIS 7 trial involving 17,263 patients undergoing PCI, a 7-day double-dose regimen of clopidogrel significantly reduced the risk of major cardiovascular events and stent thrombosis compared to the standard dose.

There was no significant difference in efficacy or safety between high-dose and low-dose aspirin, indicating that either dosage can be used without impacting outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Mehta, SR., Tanguay, JF., Eikelboom, JW., et al.[2023]

Ticagrelor is an effective antiplatelet medication used in patients with acute coronary syndrome, helping to reduce the risk of heart attacks and other cardiovascular events.

Clinical studies have shown that ticagrelor provides a greater reduction in major adverse cardiovascular events compared to traditional treatments like clopidogrel, making it a preferred choice in acute settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor (brilinta), an antiplatelet drug for acute coronary syndrome. Fuller, R., Chavez, B.[2021]

Prasugrel (Effient) has been approved by the FDA as an oral antiplatelet medication to be used alongside aspirin for reducing thrombotic cardiovascular events in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI).

This new treatment option will compete with the existing antiplatelet drug clopidogrel (Plavix), potentially offering patients and healthcare providers more choices in managing cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prasugrel (Effient) vs. clopidogrel (Plavix). [2018]

Citations

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Real-world evidence supports superior efficacy of prasugrel ... Real-world evidence supports superior efficacy of prasugrel over ticagrelor in individuals with acute coronary syndrome Free ; S Cassese · S ...

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Prasugrel versus Clopidogrel in Patients with Acute ... Prasugrel therapy was associated with significantly reduced rates of ischemic events, including stent thrombosis, but with an increased risk of major bleeding, ...

4. ahajournals.org ahajournals.org/doi/10.1161/JAHA.119.014457

Efficacy and Safety of High Potent P2Y12 Inhibitors ... Women and men had similar relative risk (RR) reduction for major cardiovascular events (women: RR, 0.89 [95% CI, 0.80–1.00; men: RR, 0.84 [95% ...

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Effectiveness of Anticlotting Medications After Stent ... Death rates were also higher for ticagrelor patients, at 5.03 percent, compared to 3.67 percent for patients taking prasugrel. Worse outcomes ...

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One-year efficacy and safety of routine prasugrel in ... All-cause mortality occurred in 1.0%, myocardial infarction in 1.5%, target-vessel revascularisation in 3.1%, stent thrombosis in 0.6%, and stroke in 0.5% of ...

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Comparative Efficacy and Safety of Oral P2Y12 Inhibitors in ... In comparison with clopidogrel, prasugrel reduced myocardial infarction (HR, 0.81 [95% CI, 0.67–0.98]), whereas ticagrelor showed no risk ...

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Ticagrelor vs Prasugrel for Acute Coronary Syndrome in ... In individuals with STEMI, prasugrel was associated with a 38% relative risk reduction for the primary end point compared with ticagrelor, ...

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Real-World Data Show Prasugrel Is More Likely to Be ... After 90 days, patients receiving prasugrel had lower rates of adverse events (9.6 percent vs. 5.7 percent, p<0.001), translating to a large (42 ...