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

Trial Summary

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 data supports the effectiveness of the drugs used in the Risk-Prevention Therapies for Coronary Artery Disease trial?

Research shows that aspirin, statins, and colchicine can help prevent heart-related events by reducing blood clots, lowering cholesterol, and decreasing inflammation. Aspirin is effective in preventing heart attacks and deaths in people who have already had a heart attack, while statins help lower cholesterol levels, reducing the risk of heart disease. ^{1 2 3 4 5}

Is aspirin generally safe for preventing heart-related events?

Aspirin is generally safe for preventing heart-related events, but it can slightly increase the risk of bleeding, such as gastrointestinal bleeding or hemorrhagic stroke. The benefits of aspirin in reducing heart events often outweigh these risks, especially for those who have already had a heart event. ^{1 2 4 6 7}

How does this drug combination prevent coronary artery disease?

This drug combination is unique because it targets multiple pathways involved in coronary artery disease: aspirin reduces blood clotting, statins lower cholesterol, colchicine reduces inflammation, and other components like Jardiance and Vascepa improve heart health through different mechanisms. This multi-faceted approach aims to prevent heart disease more effectively than using a single drug. ^{1 8 9 10 11}

What is the purpose of this trial?

The purpose of this study is to evaluate the role of coronary CT angiogram (CCTA) as a superior guide for the assessment of coronary artery plaque and guiding treatment decisions. The investigators also assess the impact of preventive cardiovascular drugs on the plaque to improve patient outcomes. Participants aged 18-80 years, at intermediate or high-risk for coronary artery disease, with non-obstructive plaque on initial CCTA, will be enrolled in this study. They will be randomized into Standard of Care (SOC) vs. Aggressive Therapy (AT) groups. Both groups will undergo dietary and lifestyle interventions. Follow-up will consist of blood tests and clinic visits at baseline, 9 months, and 18 months. The second CCTA will be performed at 18 months to assess the change in plaque burden, characteristics, ischemia and pericoronary/epicardial fat.

Research Team

Dinesh Kalra, MD

Principal Investigator

University of Louisville School of Medicine

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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]

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]

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]

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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

The role of aspirin, statins, colchicine, and IL-1 inhibitors in prevention of cardiovascular events: a systematic integrative review. [2023]

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

Prevention of recurrent myocardial infarction and sudden death with aspirin therapy. [2019]

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

The platelet in diabetes: focus on prevention of ischemic events. [2022]

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

Treatment effect of aspirin for primary prevention does not differ according to baseline ASCVD risk. [2020]

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

Primary prevention aspirin use in high-risk patients: A pharmacist intervention and comparison of risk stratification tools. [2022]

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

Primary Prevention of CVD with Aspirin: Benefits vs Risks. [2021]

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

Meta-analysis of data from the six primary prevention trials of cardiovascular events using aspirin. [2013]

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

Cardiovascular Disease Prevention: Pharmacologic Prevention. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Use of the recommended drug combination for secondary prevention after a first occurrence of acute coronary syndrome in France. [2021]

10. Italy pubmed.ncbi.nlm.nih.gov

[Low-dose aspirin in the long-term treatment of the patient with ischemic heart disease]. [2013]

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

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