Risk-Prevention Therapies for Coronary Artery Disease

(ARTCAP Trial)

Overseen By Dinesh Kalra, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Louisville

Must not be taking: Chronic immunosuppression

Disqualifiers: Heart failure, Active malignancy, Cirrhosis, ESRD, 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: 4

Duration: 18 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a coronary CT angiogram (CCTA) can better guide treatment for individuals with coronary artery disease, characterized by plaque buildup in heart arteries. Participants will be divided into two groups: one will receive standard heart care, while the other will follow a more aggressive treatment plan with medications such as statins and aspirin. Both groups will also implement lifestyle changes, and researchers will monitor their progress through blood tests and another CCTA scan after 18 months. The trial seeks participants diagnosed with plaque in their heart arteries but without major blockages. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, and it aims to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have a known intolerance or contraindication to study drugs like statins or aspirin, you may not be eligible to participate.

What is the safety track record for these treatments?

Research shows that the treatments in this study are generally well-tolerated. For example, aspirin, a common medication for heart issues, helps prevent blood clots but can increase bleeding risk. Studies have found that both low and high doses of aspirin are similarly safe.

Colchicine, another drug in this study, can reduce heart-related events in people with heart disease. It is safe at low doses but requires monitoring for side effects, especially when combined with other medications.

Jardiance (empagliflozin) has a good safety record. Long-term studies show it is safe and helps lower heart-related risks in people with diabetes.

LEQVIO (inclisiran) has been consistently safe over many years, with no new safety concerns. It is used to lower cholesterol.

Nexlizet, which combines two drugs, is also safe when used with a healthy diet and other cholesterol-lowering medicines.

Statins are well-known for lowering cholesterol and have a very low risk of causing serious muscle or liver problems.

Vascepa is safe for most people, but it can slightly increase the risk of heart rhythm issues.

All these treatments have FDA approval for other uses, indicating they are generally safe. However, each person may react differently, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for coronary artery disease because they combine multiple FDA-approved drugs, potentially enhancing the risk-prevention strategies beyond the standard care of statins and aspirin. This trial is exploring an innovative combination that includes newer agents like Jardiance and LEQVIO, which could work synergistically to further lower cholesterol levels and reduce cardiovascular risks. Jardiance, for instance, not only manages blood sugar but also offers cardiovascular benefits, while LEQVIO targets a specific protein to lower LDL cholesterol levels effectively. This multi-drug approach aims to provide a more comprehensive prevention strategy, addressing various aspects of coronary artery disease.

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

This trial will compare different treatment strategies for coronary artery disease. Research has shown that several treatments tested in this trial already help manage heart health risks. Participants in the experimental arm will receive a combination of FDA-approved drugs, including Statins, which reduce heart-related problems and deaths in people with coronary artery disease. Studies indicate that Vascepa, also part of the experimental arm, can lower the chances of heart attacks and strokes, even for those with controlled LDL cholesterol levels. Jardiance, another treatment in this arm, significantly reduces major heart issues and hospital visits for heart failure. Additionally, Nexlizet lowers LDL cholesterol and reduces inflammation, benefiting heart health. Colchicine, included in the experimental arm, reduces inflammation and can lower the risk of heart problems in people with existing coronary disease. ^{5 6 7 8 9}

Who Is on the Research Team?

Dinesh Kalra, MD

Principal Investigator

University of Louisville School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 at intermediate/high risk for heart disease, with certain types of non-obstructive plaque in their heart's arteries. Excluded are those with severe heart conditions, recent hospitalizations for heart failure, life expectancy under a year, organ transplant recipients or candidates, pregnancy or planning to conceive during the study period, known drug intolerances (like statins/aspirin), very poor kidney function, inability to receive contrast for scans and uncontrolled psychiatric illness.

Inclusion Criteria

My heart scan shows mild to moderate plaque but good blood flow in a major artery.

Exclusion Criteria

Uncontrolled psychiatric illness

LVEF <35% in the past 12 months

I was hospitalized for heart failure in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments including Polygenic Risk Score (PRS), next-generation sequencing (NGS), and echocardiographic evaluation

1-2 weeks

1 visit (in-person)

Treatment

Participants receive either Standard of Care (SOC) or Aggressive Therapy (AT) with dietary and lifestyle interventions

18 months

3 visits (in-person) at baseline, 9 months, and 18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including blood tests and repeat CCTA

5 years

Annual visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Aspirin tablet
• Colchicine
• Jardiance
• LEQVIO
• Nexlizet
• Statin
• Vascepa

Trial Overview The ART-CAP trial tests if medications like Nexlizet, Aspirin tablet, LEQVIO, Statin, Jardiance,Vascepa and Colchicine can change blood vessels in the heart. Participants will undergo CT scans to assess changes in coronary artery narrowing as part of evaluating these aggressive risk-prevention therapies.

How Is the Trial Designed?

Group I: AT: Statin, Aspirin, Nexlizet, Leqvio, Vascepa, Jardiance, Colchicine Experimental Treatment 7 Interventions

An AT group: FDA-approved drugs will be used to reduce cholesterol and cardiovascular risk.

Group II: SOC: Statin ± Aspirin (per ACC guidelines) Active Control 2 Interventions

The SOC group: participant receive routine care as per cardiologist. Study doctor will prescribe medications that they choose themselves.

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

Approved in European Union as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Myocardial infarction prevention
• Stroke prevention

Approved in United States as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Myocardial infarction prevention
• Stroke prevention

Approved in Canada as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Myocardial infarction prevention
• Stroke prevention

Approved in Japan as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Myocardial infarction prevention
• Stroke prevention

Who Is Running the Clinical Trial?

University of Louisville

Lead Sponsor

Trials

353

Recruited

76,400+

Published Research Related to This Trial

Aspirin is effective for the secondary prevention of recurrent heart attacks and death in patients who have experienced a myocardial infarction (MI) or unstable angina, especially when started soon after the initial event.

The antiplatelet effects of a single daily 325-mg aspirin tablet contribute to its efficacy, with side effects occurring in only 0-2% of patients, making it a safe option for post-MI therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of recurrent myocardial infarction and sudden death with aspirin therapy. Rumore, MM., Goldstein, GS.[2019]

Low-dose aspirin (75 to 100 mg/d) is effective in preventing cardiovascular events, especially in patients with a history of such events, where the benefits clearly outweigh the risks.

In primary prevention (for patients without a previous CV event), while low-dose aspirin reduces the risk of cardiovascular events, it also slightly increases the risk of major bleeding, suggesting that the decision to use aspirin should consider individual risk levels for both CV events and bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary Prevention of CVD with Aspirin: Benefits vs Risks. Weisman, SM., Brunton, S.[2021]

Aspirin at a dose of approximately 300 mg/day can significantly reduce the risk of myocardial infarction (MI) by about 50% in patients with moderate to high cardiovascular risk, and lower doses (150 mg/day) can decrease mortality by 23% during the acute phase of MI.

Antiplatelet agents, including aspirin and ticlopidine, are effective in preventing thrombosis after coronary surgeries and in managing conditions like cerebral ischemic accidents, highlighting their importance in both primary and secondary prevention strategies for cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors, interventions and therapeutic agents in the prevention of atherosclerosis-related ischaemic diseases. Verstraete, M.[2018]

Aspirin has been shown to be effective in preventing primary atherosclerotic cardiovascular disease, particularly as baseline risk factors for individuals increase.

The meta-regression analysis indicates that the benefits of aspirin in reducing cardiovascular events are more pronounced in populations with higher baseline risk, suggesting a tailored approach to its use in prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment effect of aspirin for primary prevention does not differ according to baseline ASCVD risk. Haley, SP., Chessman, A.[2020]

Statins are effective in preventing primary cardiovascular events by inhibiting cholesterol formation, making them a key option for individuals at risk of cardiovascular disease.

Aspirin, canakinumab, and colchicine show promise for secondary prevention of cardiovascular events by targeting inflammation pathways, but more research is needed, especially on canakinumab and colchicine, due to the limited studies available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of aspirin, statins, colchicine, and IL-1 inhibitors in prevention of cardiovascular events: a systematic integrative review. Arboleda, V., Hackworth, A., Bonnice, S., et al.[2023]

Aspirin is recommended for secondary prevention of cardiovascular disease (CVD) but should not be used for primary prevention in adults aged 60 and older; it may be considered for those aged 40 to 59 with a 10% or greater 10-year CVD risk.

Moderate- to high-intensity statin therapy is advised for most patients with known atherosclerotic CVD, high LDL cholesterol, or specific age and diabetes risk factors, while newer lipid-lowering drugs are costly and have limited evidence for reducing CVD outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Disease Prevention: Pharmacologic Prevention. Reamy, BV., Viera, AJ.[2022]

In a study of 2,057 patients who experienced their first acute coronary syndrome (ACS) in France, only 42.4% received all four recommended drug classes for secondary prevention, highlighting a gap in optimal treatment.

Persistence to treatment over 24 months was relatively low, at 57.4% for those on all four medications, with higher discontinuation rates observed in older patients and those without a myocardial infarction, indicating a need for improved adherence strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of the recommended drug combination for secondary prevention after a first occurrence of acute coronary syndrome in France. Bezin, J., Pariente, A., Lassalle, R., et al.[2021]

A meta-analysis of 6 randomized trials involving over 92,000 participants indicated that aspirin significantly reduces the risk of total coronary heart disease (CHD), nonfatal myocardial infarction (MI), and total cardiovascular (CV) events.

While aspirin showed a trend towards reducing the risk of stroke, CV mortality, and all-cause mortality, these results were not statistically significant, suggesting that aspirin's primary benefits lie in preventing specific cardiovascular events rather than overall mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of data from the six primary prevention trials of cardiovascular events using aspirin. Bartolucci, AA., Howard, G.[2013]

Low-dose enteric-coated aspirin is recommended as a primary prevention strategy for adults with diabetes at high risk for cardiovascular events, based on a meta-analysis showing its effectiveness in reducing ischemic vascular events.

In cases where aspirin is not suitable, clopidogrel is recommended, and studies indicate that combining clopidogrel with aspirin is more effective than standard therapy in reducing cardiovascular outcomes in patients with acute coronary syndromes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The platelet in diabetes: focus on prevention of ischemic events. Colwell, JA., Nesto, RW.[2022]

Aspirin is highly effective in preventing myocardial infarction and reducing mortality in patients with ischemic heart disease, making it a key treatment for both acute coronary syndromes and secondary prevention in chronic conditions.

The benefits of aspirin extend across various patient demographics, and higher doses do not provide additional effectiveness compared to lower doses, highlighting its favorable risk-to-benefit ratio compared to other antiplatelet drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Low-dose aspirin in the long-term treatment of the patient with ischemic heart disease]. Magnani, B., Semprini, F.[2013]

In a study of 116 predominantly black, middle-aged patients, only 9% were using aspirin for primary prevention of cardiovascular disease at baseline, highlighting low utilization in this underserved population.

A pharmacist-led intervention significantly increased aspirin use for primary prevention from 9% to 25%, and more patients qualified for aspirin based on ASCVD risk scores compared to the Framingham Risk Score, indicating a need for tailored risk assessment tools.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary prevention aspirin use in high-risk patients: A pharmacist intervention and comparison of risk stratification tools. Coon, SA., Brooks, AD., Wolff, SE.[2022]

Citations

1. ahajournals.org ahajournals.org/doi/abs/10.1161/circ.152.suppl_3.4339586

Abstract 4339586: Aspirin Versus P2Y12 Inhibitors as ... Regarding efficacy outcomes, no significant differences were observed. For ASA versus clopidogrel, the relative risk (RR) for the composite ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12386930/

Long-Term Effectiveness of Acetylsalicylic Acid in Primary ... Conclusions: This direct comparison of real-world age groups at high cardiovascular risk showed no benefit but increased risk in the older ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2102137

Comparative Effectiveness of Aspirin Dosing in ... In this trial, there were no significant differences in the primary effectiveness or safety outcomes between the two aspirin dosing strategies among patients ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9059243/

Aspirin and Statin Therapy for Nonobstructive Coronary ... In participants with nonobstructive CAD, baseline use of statins, but not of aspirin, was associated with improved clinical outcomes. Neither ...

5. jamanetwork.com jamanetwork.com/journals/jamacardiology/fullarticle/2820444

Aspirin Dosing for Secondary Prevention of Atherosclerotic ... No significant differences in effectiveness and safety were observed between 81-mg and 325-mg aspirin doses administered daily.

6. ahajournals.org ahajournals.org/doi/10.1161/ATVBAHA.122.318020

Aspirin for the Primary Prevention of Cardiovascular Disease Aspirin is an antiplatelet therapy drug and has been shown to protect against atherothrombosis while increasing the risk of major bleeding. •.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10743767/

Do We Still Need Aspirin in Coronary Artery Disease? - PMC Aspirin is recommended for all patients without contraindications at an initial oral loading dose of 150 to 300 mg (or 75 to 250 mg i.v.), and ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5778440/

Contemporary Reflections on the Safety of Long-Term ... Aspirin is the mainstay of secondary prevention for patients with coronary artery disease, but has a number of toxicities, including gastrointestinal discomfort ...

9. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.045010

Coronary Artery Calcium for Personalized Allocation of ... The present study aimed to assess the value of coronary artery calcium (CAC) for guiding aspirin allocation for primary prevention.