Prasugrel vs Ticagrelor for Coronary Artery Disease

(SWAP-7 Trial)

Overseen By Andrea Burton

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Florida

Must be taking: Aspirin, Prasugrel, Ticagrelor

Must not be taking: Oral anticoagulants, Heparin

Disqualifiers: Stroke, Coagulation disorders, 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: 3-4 weeks

48 Participants Needed

Trial Summary

What is the purpose of this trial?

Ticagrelor currently represents the most tested and commonly used P2Y12 inhibitor monotherapy following percutaneous coronary intervention. The purpose of this study is to conduct a head-to-head comparison on the pharmacodynamic efficacy of ticagrelor-based and prasugrel-based single antiplatelet therapy. To determine if the PD profiles of ticagrelor- and prasugrel-based SAPT are comparable, we aim to conduct a non-inferiority study between the two strategies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require participants to be on aspirin plus either prasugrel or ticagrelor for at least 90 days before joining. If you are on other medications, it's best to discuss with the trial team.

What data supports the effectiveness of the drugs Prasugrel and Ticagrelor for coronary artery disease?

Ticagrelor (Brilinta) was approved by the FDA based on the PLATO trial, which showed its effectiveness as an antiplatelet agent, meaning it helps prevent blood clots, in patients with coronary artery disease. ^{1 2 3 4 5}

Is Ticagrelor safe for humans?

Ticagrelor, used for heart conditions, has a warning for bleeding risks and may cause slow heart rates or fainting in some people. It's important to use it with low-dose aspirin to avoid reducing its effectiveness. ^{6 7 8 9 10}

How do prasugrel and ticagrelor differ from other drugs for coronary artery disease?

Prasugrel and ticagrelor are unique because they are newer antiplatelet drugs used with aspirin to prevent blood clots in patients with coronary artery disease undergoing procedures like stent placement. Ticagrelor acts faster and can be stopped more quickly than older drugs like clopidogrel, which may be beneficial in emergency situations. ^{11 12 13 14 15}

Research Team

Francesco Franchi, MD

Principal Investigator

University of Florida College of Medicine Jacksonville

Eligibility Criteria

This trial is for individuals with coronary artery disease who have undergone a procedure to open their heart's blood vessels. Participants should not be on dual antiplatelet therapy but instead need to switch to a single potent platelet blocker.

Inclusion Criteria

Able to provide written informed consent

I've been on dual antiplatelet therapy with aspirin and either prasugrel or ticagrelor for over 90 days after my stent placement.

Exclusion Criteria

Prior history of stent thrombosis

I have severe liver problems.

I have had a stroke or a transient ischemic attack (TIA).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ticagrelor or prasugrel monotherapy for 21±7 days

3-4 weeks

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Prasugrel
• Ticagrelor

Trial Overview The study compares two single antiplatelet therapies: Prasugrel (10 mg) and Ticagrelor (90 mg), after heart vessel surgery, to see which one prevents blood clots better without causing too many bleeding problems.

Participant Groups

Group I: Prasugrel monotherapy Experimental Treatment 1 Intervention

Prasugrel 10 mg qd for 21±7 days

Group II: Ticagrelor monotherapy Active Control 1 Intervention

Ticagrelor 90 mg bid monotherapy for 21±7 days

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

Approved in European Union as Effient for:

• Acute coronary syndrome

Approved in United States as Effient for:

• Acute coronary syndrome

Approved in Canada as Effient for:

• Acute coronary syndrome

Approved in Japan as Effient for:

• Acute coronary syndrome

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Findings from Research

Ticagrelor, an oral antiplatelet medication approved by the FDA, saw improved formulary placement from 2012 to 2013, becoming a preferred drug for some private insurance providers, indicating increased accessibility for patients.

However, government-funded plans, particularly Medicare and Medicaid, still have less favorable coverage for ticagrelor, which may limit its use despite its proven efficacy in reducing cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes of ticagrelor formulary tiers in the USA: targeting private insurance providers away from government-funded plans. Serebruany, VL., Dinicolantonio, JJ.[2018]

In a long-term study of 546 patients with rheumatoid arthritis (RA) who were resistant to TNF inhibitors, sarilumab demonstrated sustained efficacy over 5 years, with similar effectiveness for patients regardless of their previous TNFi failures.

The long-term safety profile of sarilumab was consistent with earlier studies, with neutropenia being the most common adverse event, affecting 14.2% of patients, but most cases normalized during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of sarilumab over 5 years in patients with rheumatoid arthritis refractory to TNF inhibitors. Fleischmann, R., Genovese, MC., Maslova, K., et al.[2021]

In a comparison of sarilumab and upadacitinib for treating rheumatoid arthritis in patients who did not respond to previous biologic DMARDs, both treatments showed similar efficacy based on data from 365 patients in the TARGET trial and 333 patients in the SELECT-BEYOND trial.

Using advanced statistical methods (MAIC and STC), the study found that the odds of achieving significant clinical improvements at 12 weeks were comparable for both medications, indicating that either could be an effective option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy of Sarilumab Versus Upadacitinib Over 12 weeks: An Indirect Treatment Comparison. Huizinga, T., Choy, E., Praestgaard, A., et al.[2023]

Switching from a tumor necrosis factor inhibitor (TNFi) to a new mechanism of action (MOA) therapy resulted in better treatment persistence compared to cycling to another TNFi, with TNFi cyclers being 51% more likely to be non-persistent.

Patients who switched to a new MOA showed a greater mean reduction in the Clinical Disease Activity Index (CDAI) compared to TNFi cyclers, although this difference was not statistically significant after adjusting for baseline disease activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Persistence and Clinical Outcomes of Tumor Necrosis Factor Inhibitor Cycling or Switching to a New Mechanism of Action Therapy: Real-world Observational Study of Rheumatoid Arthritis Patients in the United States with Prior Tumor Necrosis Factor Inhibitor Therapy. Wei, W., Knapp, K., Wang, L., et al.[2022]

Tocilizumab, when given at the approved dose of 8 mg/kg every 4 weeks in combination with methotrexate, significantly improves rheumatoid arthritis symptoms, with a higher likelihood of achieving important clinical outcomes compared to placebo, including a 38.8% response rate versus 9.6% for placebo.

While tocilizumab treatment was associated with a higher incidence of any adverse events and increased cholesterol levels, it did not lead to a significant increase in serious adverse effects or withdrawals due to adverse events, indicating a favorable safety profile overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab for rheumatoid arthritis: a Cochrane systematic review. Singh, JA., Beg, S., Lopez-Olivo, MA.[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]

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]

Ticagrelor is an effective oral antiplatelet medication commonly used in patients with acute coronary syndrome and after procedures like PCI, acting as a reversible inhibitor of the P2Y12 receptor.

Despite its efficacy, Ticagrelor can cause bradyarrhythmias and ventricular pauses, as demonstrated in a case study of a 58-year-old man who experienced syncope after loading with the drug, highlighting the need for monitoring its cardiac effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor-Induced Syncope/Bradyarrhythmia. Kotaru, V., Kalavakunta, JK.[2021]

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]

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]

In a study of 3377 patients with acute coronary syndrome treated with percutaneous coronary intervention, prasugrel was found to be superior to ticagrelor, with a lower incidence of major adverse events such as death, myocardial infarction, or stroke at 12 months.

Bleeding events were similar between the prasugrel and ticagrelor groups, indicating that while prasugrel may offer better efficacy, it does not increase the risk of bleeding compared to ticagrelor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor or Prasugrel for Patients With Acute Coronary Syndrome Treated With Percutaneous Coronary Intervention: A Prespecified Subgroup Analysis of a Randomized Clinical Trial. Coughlan, JJ., Aytekin, A., Lahu, S., et al.[2022]

In a study of 81 cardiac surgical patients, those who continued taking ticagrelor with acetylsalicylic acid (ASA) until surgery experienced significantly higher blood loss and required more blood product transfusions compared to those on clopidogrel with ASA.

Despite the increased bleeding and transfusion needs in the ticagrelor group, there were no significant differences in intensive care unit stay, hospital stay, or mortality rates, indicating that while ticagrelor may pose bleeding risks, it does not adversely affect overall survival or recovery in the short term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of cardiac surgery patients with ongoing ticagrelor therapy: boon and bane of a new drug. Schotola, H., Bräuer, A., Meyer, K., et al.[2018]

Ticagrelor is a newly licensed oral antiplatelet medication in the UK that can be used with aspirin for patients with acute coronary syndrome (ACS), potentially offering a safer alternative to traditional dual therapy with clopidogrel or prasugrel, which increases bleeding risk.

This review evaluates whether ticagrelor provides greater efficacy or a lower risk of bleeding complications compared to standard antiplatelet therapies, highlighting its potential benefits in managing ACS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor for acute coronary syndrome? [2018]

In a study of 4424 patients with acute coronary syndrome treated with dual antiplatelet therapy, prasugrel was found to be more effective than ticagrelor, showing lower rates of net adverse clinical events (NACE) and major adverse cardiovascular events (MACE) at 12 months.

Prasugrel also demonstrated a significant reduction in recurrent myocardial infarction and major bleeding events compared to ticagrelor, particularly in patients with non-ST-elevation myocardial infarction (NSTEMI), indicating its superior safety and efficacy in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data of Prasugrel vs. Ticagrelor in Acute Myocardial Infarction: Results from the RENAMI Registry. De Filippo, O., Cortese, M., D Ascenzo, F., et al.[2019]

In a review of 12 randomized controlled trials involving 2068 patients, prasugrel and ticagrelor showed similar efficacy in preventing death, myocardial infarction, stroke, and stent thrombosis after percutaneous coronary intervention (PCI).

Prasugrel was associated with a lower risk of bleeding compared to ticagrelor, particularly when assessed using the Thrombolysis in Myocardial Infarction criteria, suggesting it may be a safer option for patients in the short to mid-term following PCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Head-to-head comparison of prasugrel versus ticagrelor in patients undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials. Sakurai, R., Burazor, I., Bonneau, HN., et al.[2018]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Changes of ticagrelor formulary tiers in the USA: targeting private insurance providers away from government-funded plans. [2018]

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

Long-term safety and efficacy of sarilumab over 5 years in patients with rheumatoid arthritis refractory to TNF inhibitors. [2021]

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

Clinical Efficacy of Sarilumab Versus Upadacitinib Over 12 weeks: An Indirect Treatment Comparison. [2023]

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

Treatment Persistence and Clinical Outcomes of Tumor Necrosis Factor Inhibitor Cycling or Switching to a New Mechanism of Action Therapy: Real-world Observational Study of Rheumatoid Arthritis Patients in the United States with Prior Tumor Necrosis Factor Inhibitor Therapy. [2022]

5. Canada pubmed.ncbi.nlm.nih.gov

Tocilizumab for rheumatoid arthritis: a Cochrane systematic review. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Ticagrelor FDA approval issues revisited. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Ticagrelor: a P2Y12 antagonist for use in acute coronary syndromes. [2022]

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

Ticagrelor-Induced Syncope/Bradyarrhythmia. [2021]

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

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

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

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

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

Ticagrelor or Prasugrel for Patients With Acute Coronary Syndrome Treated With Percutaneous Coronary Intervention: A Prespecified Subgroup Analysis of a Randomized Clinical Trial. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of cardiac surgery patients with ongoing ticagrelor therapy: boon and bane of a new drug. [2018]

13. England pubmed.ncbi.nlm.nih.gov

Ticagrelor for acute coronary syndrome? [2018]

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

Real-World Data of Prasugrel vs. Ticagrelor in Acute Myocardial Infarction: Results from the RENAMI Registry. [2019]

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

Head-to-head comparison of prasugrel versus ticagrelor in patients undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials. [2018]