Aggressive Risk-Prevention Therapies for Coronary Atherosclerotic Plaque (ART-CAP)
Overview
- Phase
- Phase 4
- Intervention
- Statin
- Conditions
- Coronary Artery Disease
- Sponsor
- University of Louisville
- Enrollment
- 200
- Locations
- 1
- Primary Endpoint
- Plaque quantification
- Status
- Withdrawn
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
ART-CAP (Aggressive Risk-Prevention Therapies for Coronary Atherosclerotic Plaque ) is a prospective randomized open-label trial with blinded end-point. This research project aims to study the role of coronary computed tomographic angiography (CCTA) as a superior guide for the direct assessment and monitoring of the impact of preventive cardiovascular drugs on coronary artery plaque for better clinical decision-making and improving patient outcomes. Participants aged 18-80 years, at intermediate or high-risk (10-year ASCVD risk of 5-20% or \>20%; calculated based on age, gender, race, history of smoking, diabetes mellitus, hypertension, hyperlipidemia, and family history of premature CAD, with/without symptoms suggestive of coronary disease) who has non-obstructive plaque on CCTA (stenosis of 0-39% or 40-69% with FFR-CT \>0.8), will be enrolled. Participants with a history of heart attack, coronary stents or bypass surgery, recent stroke, severe valvular heart disease, pulmonary hypertension, NYHA class 3 or 4 heart failure, recent heart failure hospitalization, active cancer, life expectancy of \<1 year, end-stage kidney or liver disease, pregnancy or uncontrolled psychiatric illness, will be excluded. Participants will be randomly assigned to two groups - Standard of Care (SOC, 100 pts) vs. Aggressive Therapy (AT, 100 pts). Both groups will receive dietary and lifestyle interventions. SOC will be treated with statin and/or aspirin as per the ACC guidelines. AT group will be treated with statin, aspirin, nexlizet, leqvio, vascepa, jardiance, and colchicine. Follow-up will consist of blood tests and clinic visits at baseline, 9 months, and 18 months. At baseline, participants will undergo Polygenic Risk Score (PRS) and next-generation sequencing (NGS) for a South Asian gene panel. Biomarker evaluations at baseline, 9 months, and 18 months include lipid profiles, inflammatory markers, cardiac biomarkers, and buffy coat analysis for CHIP, along with standard blood tests including CBC and CMP. Additionally, echocardiographic evaluation will be performed at baseline and 18 months. After 18 months of medical treatment, a repeat CCTA will be performed to evaluate primary endpoints of the percentage change in plaque burden (total, non-calcified and calcified), plaque characteristics including high-risk features, ischemia value for the most severe lesion, and pericoronary/epicardial fat attenuation. Patient will be followed for additional 5 years for MACCE (major adverse cardiovascular and cerebrovascular events).
Investigators
Dinesh Kalra, MD
Professor, MD
University of Louisville
Eligibility Criteria
Inclusion Criteria
- •Non-obstructive atherosclerotic coronary artery plaque (stenosis of 0-39% or stenosis of 40-69% with FFR-CT \>0.8) in a major epicardial vessel \> 2 mm in diameter.
Exclusion Criteria
- •coronary/PAD/carotid revascularization or ischemic stroke or TIA within 6 months prior to enrollment
- •Valvular heart disease of moderate or worse severity or requiring interventional procedures or surgery
- •LVEF \<35% in the past 12 months
- •Pulmonary hypertension with PASP\>50 mm Hg in the past 12 months
- •Myocarditis or pericarditis in the past 12 months
- •Known Cardiomyopathy (hypertrophic, infiltrative, restrictive, dilated, etc.)
- •Heart failure NYHA class 3 or 4
- •Hospitalization for heart failure in the preceding 6 months
- •Life expectancy of \<1 year
- •An organ-transplant recipient or if felt to require listing for solid organ transplantation during study status
Arms & Interventions
SOC: Statin ± Aspirin (per ACC guidelines)
The SOC group: participant receive routine care as per cardiologist. Study doctor will prescribe medications that they choose themselves.
Intervention: Statin
SOC: Statin ± Aspirin (per ACC guidelines)
The SOC group: participant receive routine care as per cardiologist. Study doctor will prescribe medications that they choose themselves.
Intervention: Aspirin tablet
AT: Statin, Aspirin, Nexlizet, Leqvio, Vascepa, Jardiance, Colchicine
An AT group: FDA-approved drugs will be used to reduce cholesterol and cardiovascular risk.
Intervention: Statin
AT: Statin, Aspirin, Nexlizet, Leqvio, Vascepa, Jardiance, Colchicine
An AT group: FDA-approved drugs will be used to reduce cholesterol and cardiovascular risk.
Intervention: Aspirin tablet
AT: Statin, Aspirin, Nexlizet, Leqvio, Vascepa, Jardiance, Colchicine
An AT group: FDA-approved drugs will be used to reduce cholesterol and cardiovascular risk.
Intervention: Nexlizet
AT: Statin, Aspirin, Nexlizet, Leqvio, Vascepa, Jardiance, Colchicine
An AT group: FDA-approved drugs will be used to reduce cholesterol and cardiovascular risk.
Intervention: LEQVIO
AT: Statin, Aspirin, Nexlizet, Leqvio, Vascepa, Jardiance, Colchicine
An AT group: FDA-approved drugs will be used to reduce cholesterol and cardiovascular risk.
Intervention: Vascepa
AT: Statin, Aspirin, Nexlizet, Leqvio, Vascepa, Jardiance, Colchicine
An AT group: FDA-approved drugs will be used to reduce cholesterol and cardiovascular risk.
Intervention: Jardiance
AT: Statin, Aspirin, Nexlizet, Leqvio, Vascepa, Jardiance, Colchicine
An AT group: FDA-approved drugs will be used to reduce cholesterol and cardiovascular risk.
Intervention: Colchicine
Outcomes
Primary Outcomes
Plaque quantification
Time Frame: Baseline, 18 months
Quantification of plaque including total plaque, calcified plaque, non-calcified plaque, and partially calcified plaque. Units: mm3
Characterization of plaque to evaluate for high-risk features - positive remodeling
Time Frame: Baseline, 18 months
Characterization of plaque to evaluate for high-risk features - positive remodeling Units: no units (yes or no)
Quantification of stenosis
Time Frame: Baseline, 18 months
Quantification of stenosis by using CT-FFR. Unit: percentage
Quantification of pericoronary fat attenuation.
Time Frame: Baseline, 18 months
Quantification of pericoronary and epicardial fat attenuation. Unit: Fat attenuation index \[ranging from -190 to -30 Hounsfield units (HU)\]
Characterization of plaque to evaluate for high-risk features - napkin-ring sign
Time Frame: Baseline, 18 months
Characterization of plaque to evaluate for high-risk features - napkin-ring sign Units: no units (yes or no)
Characterization of plaque to evaluate for high-risk features - low CT attenuation
Time Frame: Baseline, 18 months
Characterization of plaque to evaluate for high-risk features - low CT attenuation Units: no units (yes or no)
Quantification of epicardial fat attenuation.
Time Frame: Baseline, 18 months
Quantification of epicardial fat attenuation. Unit: Fat attenuation index \[ranging from -190 to -30 Hounsfield units (HU)\]
Secondary Outcomes
- Major adverse cardiac and cardiovascular events (MACCE)(5 years)
- Polygenic risk score (PRS)(Baseline)
- Change in Lipoprotein (a)(Baseline, 9 and 18 months)
- Change in lipoprotein-associated phospholipase A2 (Lp-PLA2) levels(Baseline, 9 and 18 months)
- Change in interleukin-6 (IL-6) levels(Baseline, 9 and 18 months)
- Next generation sequencing (NGS)(Baseline)
- Change in myeloperoxidase (MPO) activity(Baseline, 9 and 18 months)
- Change in trimethylamine-N-oxide (TMAO) levels(Baseline, 9 and 18 months)
- Change in high sensitivity C-creative protein (HS-CRP) levels(Baseline, 9 and 18 months)
- Buffy coat for chromatin immunoprecipitation (ChIP)(Baseline, 9 and 18 months)
- Change in high sensitivity Troponin (HS-Tn)(Baseline, 9 and 18 months)
- Change in natriuretic peptide (BNP, NT-pro BNP(Baseline, 9 and 18 months)
- Change in levels of open reading frame 1 protein (ORF1p)(Baseline, 9 and 18 months)