Aggressive Risk-Prevention Therapies for Coronary Atherosclerotic Plaque (ART-CAP)
- Conditions
- AtherosclerosisCoronary Artery DiseaseHeart Attack
- Interventions
- Registration Number
- NCT06280976
- Lead Sponsor
- University of Louisville
- 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).
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- 200
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.
- 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
- Inability to give informed consent
- Active malignancy (except basal cell skin cancer)
- Cirrhosis
- ESRD
- Pregnancy or planning to conceive during the study period
- Known intolerance or perceived contraindication to any of the study drugs during the study period including statins or aspirin if indicated
- eGFR<30 ml/min/m2
- Inability to receive iodinated contrast for CCTA
- Chronic immunosuppression therapy
- Uncontrolled psychiatric illness
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AT: Statin, Aspirin, Nexlizet, Leqvio, Vascepa, Jardiance, Colchicine LEQVIO An AT group: FDA-approved drugs will be used to reduce cholesterol and cardiovascular risk. AT: Statin, Aspirin, Nexlizet, Leqvio, Vascepa, Jardiance, Colchicine Aspirin tablet An AT group: FDA-approved drugs will be used to reduce cholesterol and cardiovascular risk. SOC: Statin ± Aspirin (per ACC guidelines) Statin The SOC group: participant receive routine care as per cardiologist. Study doctor will prescribe medications that they choose themselves. SOC: Statin ± Aspirin (per ACC guidelines) Aspirin tablet The SOC group: participant receive routine care as per cardiologist. Study doctor will prescribe medications that they choose themselves. AT: Statin, Aspirin, Nexlizet, Leqvio, Vascepa, Jardiance, Colchicine Jardiance An AT group: FDA-approved drugs will be used to reduce cholesterol and cardiovascular risk. AT: Statin, Aspirin, Nexlizet, Leqvio, Vascepa, Jardiance, Colchicine Nexlizet An AT group: FDA-approved drugs will be used to reduce cholesterol and cardiovascular risk. AT: Statin, Aspirin, Nexlizet, Leqvio, Vascepa, Jardiance, Colchicine Statin An AT group: FDA-approved drugs will be used to reduce cholesterol and cardiovascular risk. AT: Statin, Aspirin, Nexlizet, Leqvio, Vascepa, Jardiance, Colchicine Vascepa An AT group: FDA-approved drugs will be used to reduce cholesterol and cardiovascular risk. AT: Statin, Aspirin, Nexlizet, Leqvio, Vascepa, Jardiance, Colchicine Colchicine An AT group: FDA-approved drugs will be used to reduce cholesterol and cardiovascular risk.
- Primary Outcome Measures
Name Time Method Plaque quantification 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 Baseline, 18 months Characterization of plaque to evaluate for high-risk features - positive remodeling Units: no units (yes or no)
Quantification of stenosis Baseline, 18 months Quantification of stenosis by using CT-FFR. Unit: percentage
Quantification of pericoronary fat attenuation. 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 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 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. Baseline, 18 months Quantification of epicardial fat attenuation. Unit: Fat attenuation index \[ranging from -190 to -30 Hounsfield units (HU)\]
- Secondary Outcome Measures
Name Time Method Major adverse cardiac and cardiovascular events (MACCE) 5 years Number of participants with adjusted events including non-fatal myocardial infarction, stroke, transient ischemic attack, urgent revascularization, cardiovascular hospitalization, hospitalization for heart failure, and cardiovascular death.
Unit: number of eventsPolygenic risk score (PRS) Baseline Polygenic risk score (PRS) to estimate the participant's genetic susceptibility for coronary artery disease, assessed via blood draw.
Unit: No units (weighted score ranging from 0-100)Change in Lipoprotein (a) Baseline, 9 and 18 months Change in Lipoprotein (a) level as assessed via blood draw. Unit: nmol/L
Change in lipoprotein-associated phospholipase A2 (Lp-PLA2) levels Baseline, 9 and 18 months Change in lipoprotein-associated phospholipase A2 (Lp-PLA2) levels, as assessed by blood draw.
Unit: ng/mLChange in interleukin-6 (IL-6) levels Baseline, 9 and 18 months Change in interleukin-6 (IL-6) levels, as assessed by blood draw. Unit: pg/mL
Next generation sequencing (NGS) Baseline Next generation sequencing (NGS) to identify mutations associated with coronary artery disease, assessed via blood draw.
Unit: Mutation in disease-genesChange in myeloperoxidase (MPO) activity Baseline, 9 and 18 months Change in myeloperoxidase (MPO) activity, as assessed via blood draw. Unit: μU/mg
Change in trimethylamine-N-oxide (TMAO) levels Baseline, 9 and 18 months Change in trimethylamine-N-oxide (TMAO) levels, assessed via blood draw. Unit: µM
Change in high sensitivity C-creative protein (HS-CRP) levels Baseline, 9 and 18 months Change in high sensitivity C-creative protein (HS-CRP) levels as assessed by blood draw.
Units: mg/mLBuffy coat for chromatin immunoprecipitation (ChIP) Baseline, 9 and 18 months Buffy coat for chromatin immunoprecipitation (ChIP) as assessed by blood draw. Unit: Genomic locations of binding of various proteins involved in coronary plaque formation
Change in high sensitivity Troponin (HS-Tn) Baseline, 9 and 18 months Change in high sensitivity Troponin (HS-Tn), as assessed by blood draw. Unit: ng/mL
Change in natriuretic peptide (BNP, NT-pro BNP Baseline, 9 and 18 months Change in natriuretic peptide (BNP, NT-pro BNP), as assessed by blood draw. Unit: pg/mL
Change in levels of open reading frame 1 protein (ORF1p) Baseline, 9 and 18 months Change in levels of open reading frame 1 protein (ORF1p), as assessed by blood draw using enzyme-linked immunosorbent assay (ELISA) or western blotting.
Unit: μg/mL
Trial Locations
- Locations (1)
University of Louisville School of Medicine, Division of Cardiovascular Diseases
🇺🇸Louisville, Kentucky, United States