Ticagrelor vs. Clopidogrel for Coronary Artery Disease

Overseen By Andrea Burton, MPH, CPH

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Florida

Must be taking: Aspirin, Clopidogrel

Must not be taking: Prasugrel, Ticagrelor

Disqualifiers: Myocardial infarction, Anticoagulants, Liver disease, 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

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

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two medications, ticagrelor (also known as Brilinta, Brilique, or Possia) and clopidogrel (also known as Plavix), to determine which is more effective for individuals with stable coronary artery disease undergoing elective PCI. Researchers believe ticagrelor may reduce platelet activity more effectively, which is crucial for preventing blood clots. Participants should have stable coronary artery disease, be scheduled for elective PCI, and have been taking aspirin and clopidogrel. This trial may suit those who haven't had a recent heart attack, have been on specific medications, and meet a particular genetic score. As a Phase 4 trial, this research involves FDA-approved treatments and aims to understand how they benefit more patients.

Will I have to stop taking my current medications?

The trial requires participants to be on low-dose aspirin and clopidogrel for at least 24 hours after the procedure. If you are currently taking prasugrel, ticagrelor, or certain other medications, you may need to stop those before joining the trial.

What is the safety track record for these treatments?

Research has shown that ticagrelor is generally safe, but some risks exist. One study found that ticagrelor reduced the chances of serious heart problems, such as heart attacks and strokes, compared to clopidogrel. However, it also increased the risk of major bleeding, an important trade-off to consider.

Another study found that using ticagrelor with aspirin reduced the risk of serious heart issues but led to more significant bleeding than a placebo. The FDA has approved ticagrelor for treating certain heart conditions, indicating that its safety has been carefully reviewed.

Prospective clinical trial participants should weigh the benefits against the risk of bleeding. Discussing options with a healthcare provider is crucial to making the best decision for one's health. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about ticagrelor for coronary artery disease because it offers a different mechanism of action compared to traditional treatments like clopidogrel. Unlike clopidogrel, which needs to be metabolized to become active, ticagrelor works directly and more rapidly by reversibly binding to the P2Y12 receptor on platelets. This direct action may lead to more consistent and reliable platelet inhibition. Moreover, ticagrelor has been shown to potentially reduce the risk of clot-related events more effectively, making it a promising option for patients undergoing procedures like elective PCI.

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

Research has shown that ticagrelor can reduce serious heart issues, such as heart attacks, strokes, and death from heart problems, in people with coronary artery disease (CAD). One study found that ticagrelor users had a 14.9% lower risk of these issues compared to those taking clopidogrel. Another study demonstrated that using ticagrelor with aspirin lowered the chance of heart problems related to blood flow, though it also increased the risk of major bleeding. In this trial, participants will be randomly assigned to either switch to ticagrelor or continue with clopidogrel. Ticagrelor is approved for patients with high-risk CAD, indicating its proven effectiveness for them. This evidence suggests it could be effective for patients with a high ABCD-GENE score. ^{1 2 3 4 5}

Who Is on the Research Team?

Francesco Franchi, MD

Principal Investigator

Univesrsity of Florida

Are You a Good Fit for This Trial?

This trial is for stable coronary artery disease patients undergoing elective heart procedure (PCI), aged 18 or older, with no recent heart attack and on low-dose aspirin plus clopidogrel. They must have a high genetic risk score (ABCD-GENE ≥10) and normal or slightly elevated troponin levels. Excluded are those with allergies to the drugs being tested, certain other medications, severe liver disease, low blood counts, potential bradycardia without a pacemaker, active bleeding issues, or women not using contraception.

Inclusion Criteria

Troponin negative before coronary angiography

My ABCD-GENE score is 10 or higher.

I have stable heart artery disease and am scheduled for a procedure to open my heart's arteries.

Exclusion Criteria

Known platelet count <80x106/mL

Known hemoglobin <9 g/dL

Women of child-bearing potential (i.e., those who are not chemically or surgically sterilized or who are not post-menopause) who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator OR who have a positive pregnancy test at enrollment or randomization OR women who are breast-feeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either low-dose ticagrelor or clopidogrel to assess antiplatelet effects

4 weeks

1 visit (in-person) for PCI, followed by regular monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including platelet reactivity measurements

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Clopidogrel
• Ticagrelor

Trial Overview The study compares the effects of two blood-thinning medications in preventing clot formation after PCI: Ticagrelor (60 mg twice daily) versus Clopidogrel. It aims to see if Ticagrelor offers better protection against platelet reactivity in high-risk genetic profile patients.

How Is the Trial Designed?

Group I: Low-dose ticagrelor Experimental Treatment 1 Intervention

Stable CAD patients undergoing elective PCI treated with standard of care clopidogrel will be randomly assigned in a 1:1 fashion to either switch to ticagrelor or continue with clopidogrel.

Group II: Clopidogrel Active Control 1 Intervention

Stable CAD patients undergoing elective PCI treated with standard of care clopidogrel will be randomly assigned in a 1:1 fashion to either switch to ticagrelor or continue with clopidogrel.

Ticagrelor is already approved in United States, European Union for the following indications:

Approved in United States as Brilinta for:

• Acute coronary syndrome (ACS)
• Cardiovascular event prevention
• Coronary artery disease (CAD)
• Acute ischemic stroke
• Transient ischemic attack (TIA)

Approved in European Union as Brilique for:

• Acute coronary syndrome (ACS)
• Cardiovascular event prevention
• Coronary artery disease (CAD)
• Acute ischemic stroke
• Transient ischemic attack (TIA)

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Scott R. MacKenzie Foundation

Collaborator

Trials

5

Recruited

510+

Published Research Related to This Trial

In the large PLATO study involving adult patients with acute coronary syndromes (ACS), ticagrelor was found to be more effective than clopidogrel in reducing the risk of major cardiovascular events, including myocardial infarction and stroke, while also showing a trend towards reduced all-cause mortality.

Ticagrelor was generally well tolerated, with no increased risk of major bleeding compared to clopidogrel, although it did have higher rates of certain non-hemorrhagic side effects like dyspnea and ventricular pauses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor: a review of its use in adults with acute coronary syndromes. Dhillon, S.[2018]

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™) 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 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 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, a potent oral platelet inhibitor, significantly reduces the risk of death, myocardial infarction, or stroke in patients with acute coronary syndromes compared to clopidogrel, as shown in the PLATO study.

While ticagrelor does not increase the overall rate of major bleeding compared to clopidogrel, it is associated with a higher incidence of non-procedure-related bleeding, indicating a need for careful monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Medication of the month. Ticagrelor (Brilique): potent oral antagonist of platelet activity]. Lancellotti, P.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24952862/

Extent of coronary artery disease and outcomes after ... Ticagrelor, compared with clopidogrel, reduced the composite of cardiovascular death, myocardial infarction, and stroke in patients with extensive CAD (14.9% ...

2. academic.oup.com academic.oup.com/ejcts/article/67/7/ezaf175/8145572

Extent of coronary artery disease and clinical outcomes with ... In this post hoc analysis of the TICAB trial, we found no significant difference in the effect of ticagrelor monotherapy compared to aspirin on ...

3. ahajournals.org ahajournals.org/doi/10.1161/JAHA.123.031606

Review of the Ticagrelor Trials Evidence Base In the CHANCE trial, the 90‐day outcome of ischemic or hemorrhagic stroke in Chinese patients was reduced (8.2% versus 11.7%; HR, 0.68 [95% CI, ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1908077

Ticagrelor in Patients with Stable Coronary Disease and ... Ticagrelor plus aspirin had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus ...

5. brilintahcp.com brilintahcp.com/cad.html

Coronary Artery Disease (CAD) | BRILINTA | For HCPs BRILINTA® (ticagrelor) is indicated for treatment in patients with high-risk coronary artery disease (CAD) without history of MI or stroke.