A Randomized Comparison of Stage-Based Care Versus Risk Factor-Based Care for Prevention of Cardiovascular Events

NCT ID: NCT06112418

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

7500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-06

Study Completion Date

2029-03-05

Brief Summary

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TRANSFORM is a prospective, randomized, open blinded endpoint (PROBE), event-driven, pragmatic trial in patients who are at increased risk for atherosclerotic cardiovascular (CV) disease but with no known symptomatic CV disease. The trial tests the hypothesis that a Cleerly Coronary Artery Disease (CAD) Staging System-based care strategy reduces CV events compared with risk factor-based care.

Detailed Description

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Cardiovascular disease (CVD) persists as the leading cause of morbidity and mortality worldwide at high societal cost. The current primary CVD prevention strategy relies upon risk stratification using population health markers such as age, sex, diabetes, hypertension, dyslipidemia and tobacco use, with preventive therapy intensified in higher risk strata. Since these risk factors are indirect surrogate markers of the underlying disease, atherosclerosis, this strategy leads to treatment of individuals with risk factors who do not have atherosclerosis and failure to treat those with significant atherosclerosis who lack risk factors. The current strategy also cannot determine which individuals are inadequately treated despite effective risk factor management (residual risk). With the current approach, the CV death rate is trending upward in the US despite evidence that screening asymptomatic patients reduces CV events and the widespread availability of effective preventive therapies.

This randomized, controlled, pragmatic trial is designed to address the unmet need for better strategies to identify asymptomatic individuals at increased risk for CV events due to atherosclerosis and to personalize their treatment based on CV risk estimates using coronary artery disease (CAD) visualization and quantification.

This study enrolls patients without known symptoms of ASCVD but who are at increased risk for ASCVD due to their age and having diabetes, prediabetes or metabolic syndrome and tests the hypothesis that a CAD Staging System-based care strategy reduces CV events compared with risk factor-based care. The Cleerly CAD Staging System incorporates imaging-based evaluation for coronary atherosclerosis, algorithm-supported pharmacotherapy and personalized education about their CAD.

Conditions

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Diabetes Mellitus, Type 2 PreDiabetes Metabolic Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective, randomized, open blinded endpoint (PROBE), event-driven pragmatic trial
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Risk Factor-Based Care

The risk factor-based care group will be managed by their usual care providers, with an initial pre-randomization assessment of current treatment by a centralized cardiology team to optimize care relative to primary prevention guidelines. During the trial, the centralized cardiology team will monitor the provision of medications prescribed and lab values relative to guidelines, and provide feedback and education to site investigators to support optimization. CCTA results will be centrally archived and will remain blinded to the usual care provider until the end of the study.

Group Type NO_INTERVENTION

No interventions assigned to this group

Cleerly Stage-Based Care

The Cleerly Stage-Based Care group will receive personalized care centrally managed by a remote cardiologist-led team. They will also receive an initial pre-randomization assessment of current treatment by a centralized cardiology team to optimize care relative to primary prevention guidelines. Cleerly CAD Staging System results will be discussed with participants and serve as the basis for standardized algorithm-supported pharmacotherapy \& education, which will be intensified if plaque burden has progressed at 24 months.

Group Type EXPERIMENTAL

The Cleerly CAD Staging System

Intervention Type DEVICE

The Cleerly CAD Staging System is software that utilizes a proprietary algorithm to identify CAD, stage the severity of CAD when present, and generate a prognostic risk score to inform treatment decisions that support CV disease prevention.

Interventions

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The Cleerly CAD Staging System

The Cleerly CAD Staging System is software that utilizes a proprietary algorithm to identify CAD, stage the severity of CAD when present, and generate a prognostic risk score to inform treatment decisions that support CV disease prevention.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

1. Provided electronic or written informed consent
2. Men \> 55, women \> 65 years of age
3. Type 2 diabetes mellitus requiring pharmacologic therapy, prediabetes (most recent HbA1c 5.7 to 6.4% and/or fasting glucose 100-125 mg/dL \[5.6-6.9 mmol/L\]) and/or metabolic syndrome. Metabolic syndrome is defined as \> 3 of the following criteria (International Diabetes Federation 2006):

* Body mass index ≥ 27 kg/m2 or abnormal waist circumference defined as ≥ 80 cm (31.5 inches) for women, ≥ 94 cm (37 inches) for men; for South and East Asian men (e.g., Asian Indian, Chinese, Japanese) ≥ 90 cm (35.4 inches)
* Fasting triglycerides ≥ 150 mg/dL (1.7 mmol/L) or treated hypertriglyceridemia
* HDL-cholesterol (HDL-C) \< 40 mg/dL (1.03 mmol/L) in men, \<50 mg/dL (1.29 mmol/L) in women or treatment for this lipid abnormality
* Systolic blood pressure (BP) ≥ 130 and/or diastolic BP≥ 85 mm Hg and/or treated hypertension
* Fasting blood glucose ≥ 100 mg/dL (5.6 mmol/L) or HbA1c ≥ 5.7%
4. Have a device (e.g., smartphone, tablet, computer) for communication with the central cardiologist-led team managing drug treatment for the personalized care group

Exclusion Criteria

1. History of symptomatic CVD defined as prior MI, exertional or unstable angina, ischemic stroke, claudication, arterial revascularization for atherosclerosis or other CVD being actively managed by a cardiologist, e.g. atrial fibrillation, heart failure
2. Planned arterial revascularization
3. Inability to complete screening CCTA or any condition that would increase the risk associated with CCTA or increase likelihood of uninterpretable scan including:

1. eGFR \< 60 mL/min/1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) or Modification of Diet in Renal Disease (MDRD) equation (www.kidney.org/professionals/kdoqi/gfr\_calculator)
2. Allergy to iodinated contrast or history of contrast-induced nephropathy (including adverse reaction to contrast at screening CCTA) or screening laboratory values consistent with untreated hyperthyroidism. Participants with elevated thyroid-stimulating hormone (TSH) may be enrolled but should be referred to their physician for evaluation for treatment.
3. Thyroid cancer in the previous five (5) years or planned radioactive iodine treatment
4. Weight \> 300 lbs. (136 kg) or above manufacturer-recommended limit for scanner and table at the site
5. Inability to hold breath for \> 10 seconds
6. Active arrhythmia (atrial fibrillation, atrial flutter, frequent premature atrial, or ventricular contractions) with poorly controlled rate (i.e., \> 80 beats per minute at screening or prior to CCTA)
7. Contraindication to dosing with beta blocker or nitroglycerin on day of screening CCTA
8. Any other factor that, in the opinion of the investigator, would increase participant risk or increase the chance of an uninterpretable CCTA
4. Unsuitable as a trial participant in the opinion of the investigator for reasons including significant left main stenosis (e.g. ≥ 70%; site will be notified by Cleerly), other health condition with life expectancy \< 3 years or being at risk of poor compliance with study procedures (e.g., active substance abuse or untreated mental illness that, in the opinion of the investigator, is likely to adversely affect adherence or retention)
Minimum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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CPC Clinical Research

UNKNOWN

Sponsor Role collaborator

Cleerly, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Deepak Bhatt, MD, MPH

Role: STUDY_CHAIR

Mt. Sinai Heart

Locations

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Chandler Clinical Trials

Chandler, Arizona, United States

Site Status RECRUITING

Scottsdale Clinical Trials

Scottsdale, Arizona, United States

Site Status RECRUITING

Sun City Research

Sun City, Arizona, United States

Site Status RECRUITING

Noble Clinical Research

Tucson, Arizona, United States

Site Status RECRUITING

Cardiovascular Research Foundation of Southern California

Beverly Hills, California, United States

Site Status RECRUITING

Amicis Research: Beverly Hills

Beverly Hills, California, United States

Site Status RECRUITING

Valiance Clinical Research - Canoga Park

Canoga Park, California, United States

Site Status RECRUITING

Cardiovascular Institute of San Diego

Chula Vista, California, United States

Site Status RECRUITING

Amicis Research: Granada Hills

Granada Hills, California, United States

Site Status RECRUITING

Valiance Clinical Research: Huntington Park

Huntington Park, California, United States

Site Status RECRUITING

HALO Diagnostics

Indian Wells, California, United States

Site Status RECRUITING

Chemidox Clinical Trials

Lancaster, California, United States

Site Status RECRUITING

Long Beach Research Institute

Long Beach, California, United States

Site Status RECRUITING

Ace Research Institute - Monterey Park

Monterey Park, California, United States

Site Status RECRUITING

Amicis Research: Newhall

Newhall, California, United States

Site Status RECRUITING

Ace Research Institute: Northridge

Northridge, California, United States

Site Status RECRUITING

Amicis Research: Northridge

Northridge, California, United States

Site Status RECRUITING

Ace Research Institute: Northridge #2

Northridge, California, United States

Site Status RECRUITING

Northridge Clinical Trials

Northridge, California, United States

Site Status RECRUITING

Stanford Health Care

Palo Alto, California, United States

Site Status RECRUITING

VA Palo Alto

Palo Alto, California, United States

Site Status RECRUITING

Amicis Research: San Fernando

San Fernando, California, United States

Site Status RECRUITING

Valiance Clinical Research - Tarzana

Tarzana, California, United States

Site Status RECRUITING

Lundquist Institute for Biomedical Innovation at Harbor - UCLA Medical Center

Torrance, California, United States

Site Status RECRUITING

Amicis Research: Valencia

Valencia, California, United States

Site Status RECRUITING

University of Colorado

Aurora, Colorado, United States

Site Status RECRUITING

St. Josephs (Intermountain Healthcare)

Denver, Colorado, United States

Site Status RECRUITING

Flourish Medical Research

Boca Raton, Florida, United States

Site Status RECRUITING

Apex Research

Cross City, Florida, United States

Site Status RECRUITING

Evolution Research Center

Hialeah, Florida, United States

Site Status RECRUITING

UF Health Jacksonville

Jacksonville, Florida, United States

Site Status RECRUITING

Fiel Wellness Clinical Research LLC

Miami, Florida, United States

Site Status RECRUITING

BioPhase Research

Miami, Florida, United States

Site Status RECRUITING

United Clinical Research

Miami, Florida, United States

Site Status RECRUITING

Atlantis Clinical Research, LLC

Miami, Florida, United States

Site Status RECRUITING

Baptist Health Miami Cardiac and Vascular Institute

Miami, Florida, United States

Site Status RECRUITING

Farma Medical Inc.

Miami, Florida, United States

Site Status RECRUITING

New Access Research and Medical Center

Miami, Florida, United States

Site Status RECRUITING

Quantum Clinical Trials

Miami Beach, Florida, United States

Site Status RECRUITING

Ascension Sacred Heart

Pensacola, Florida, United States

Site Status RECRUITING

Clinical Research Center of Florida

Pompano Beach, Florida, United States

Site Status RECRUITING

University of South Florida

Tampa, Florida, United States

Site Status RECRUITING

Aiyan Diabetes Center

Augusta, Georgia, United States

Site Status RECRUITING

Emory University

Dunwoody, Georgia, United States

Site Status RECRUITING

Peachtree Clinical Solutions - Noir Research Collective

Powder Springs, Georgia, United States

Site Status RECRUITING

Randomize Now, LLC - Noir Research Collective

Riverdale, Georgia, United States

Site Status RECRUITING

Privia Medical Group Georgia, LLC (Javara Inc.)

Savannah, Georgia, United States

Site Status RECRUITING

Care Institute- High Desert

Meridian, Idaho, United States

Site Status RECRUITING

Northshore University Health System

Evanston, Illinois, United States

Site Status RECRUITING

Indiana Medical Research Institute

Indianapolis, Indiana, United States

Site Status RECRUITING

Franciscan Physician Network- Indiana Heart Physicians

Indianapolis, Indiana, United States

Site Status RECRUITING

MercyOne Iowa Heart Center

West Des Moines, Iowa, United States

Site Status RECRUITING

St Elizabeth Health Care - CRI

Edgewood, Kentucky, United States

Site Status RECRUITING

UofL Health

Louisville, Kentucky, United States

Site Status RECRUITING

Flourish Bowie dba Flourish Research

Bowie, Maryland, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Henry Ford Hospital

Detroit, Michigan, United States

Site Status RECRUITING

Trinity Health Michigan Heart

Ypsilanti, Michigan, United States

Site Status RECRUITING

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Saint Louis Heart and Vascular

St Louis, Missouri, United States

Site Status RECRUITING

Boeson Research Kalispell

Kalispell, Montana, United States

Site Status RECRUITING

Boeson Research Fort Missoula

Missoula, Montana, United States

Site Status RECRUITING

Bryan Heart

Lincoln, Nebraska, United States

Site Status RECRUITING

Southwest Medical Associates- Optum Nevada

Las Vegas, Nevada, United States

Site Status RECRUITING

Vector Clinical Trials

Las Vegas, Nevada, United States

Site Status RECRUITING

Advanced Heart and Vascular Institute of Hunterdon

Flemington, New Jersey, United States

Site Status RECRUITING

Virtua Health, Inc.

Marlton, New Jersey, United States

Site Status RECRUITING

Rutgers State University

New Brunswick, New Jersey, United States

Site Status RECRUITING

The Valley Hospital

Paramus, New Jersey, United States

Site Status RECRUITING

Holy Name Medical Center

Teaneck, New Jersey, United States

Site Status RECRUITING

Clindove Research

Brooklyn, New York, United States

Site Status RECRUITING

Swift Clinical Research

Brooklyn, New York, United States

Site Status RECRUITING

Rasaj Research

Jackson Heights, New York, United States

Site Status RECRUITING

Optum- Long Island NY

Lake Success, New York, United States

Site Status RECRUITING

Northwell Health Northern Westchester Hospital

Mount Kisco, New York, United States

Site Status RECRUITING

Mount Sinai West

New York, New York, United States

Site Status RECRUITING

Mount Sinai

New York, New York, United States

Site Status RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Duke University Hospital

Durham, North Carolina, United States

Site Status RECRUITING

Cape Fear Valley Health System (Javara Inc.)

Fayetteville, North Carolina, United States

Site Status RECRUITING

West Clinical Research

Morehead City, North Carolina, United States

Site Status RECRUITING

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status RECRUITING

Sanford Health

Fargo, North Dakota, United States

Site Status RECRUITING

Summa Health

Akron, Ohio, United States

Site Status RECRUITING

Hightower Clinical

Oklahoma City, Oklahoma, United States

Site Status RECRUITING

Medical Research International, LLC

Oklahoma City, Oklahoma, United States

Site Status RECRUITING

Ascension St. John - Jane Phillips Medical Center

Tulsa, Oklahoma, United States

Site Status RECRUITING

Capital Area Research

Camp Hill, Pennsylvania, United States

Site Status RECRUITING

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status RECRUITING

Community DPC

Cleveland, Tennessee, United States

Site Status RECRUITING

University of Tennessee Medical Center

Knoxville, Tennessee, United States

Site Status RECRUITING

TriStar Centennial Medical Center (HCA Health Care)

Nashville, Tennessee, United States

Site Status RECRUITING

Hendrick Health

Abilene, Texas, United States

Site Status RECRUITING

Gadolin Research

Beaumont, Texas, United States

Site Status RECRUITING

CardioVoyage, LLC

Greenville, Texas, United States

Site Status RECRUITING

Helium Research Group

Houston, Texas, United States

Site Status RECRUITING

Kelsey Research Foundation

Houston, Texas, United States

Site Status RECRUITING

The Methodist Hospital, DeBakey Cardiology Associates

Houston, Texas, United States

Site Status RECRUITING

Gulf Coast Clinical Research, LLC

Houston, Texas, United States

Site Status RECRUITING

Aeres Clinical Research

Laredo, Texas, United States

Site Status RECRUITING

DC Clinical Research

Lewisville, Texas, United States

Site Status RECRUITING

North Dallas Research Associates - Kerlo Network

McKinney, Texas, United States

Site Status RECRUITING

SMS Clinical Research

Mesquite, Texas, United States

Site Status RECRUITING

Privia Medical Group Gulf Coast, PLLC ( Javara Inc.)

San Marcos, Texas, United States

Site Status RECRUITING

Privia Medical Group- North Texas

Stephenville, Texas, United States

Site Status RECRUITING

Chippenham Johnston Willis Medical Center

Richmond, Virginia, United States

Site Status RECRUITING

Charleston Area Medical Center

Charleston, West Virginia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Ryann Sardinia

Role: CONTACT

Phone: 7207398191

Email: [email protected]

Ashley Dunham, PhD

Role: CONTACT

Phone: 7207398191

Email: [email protected]

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Muhammad Salim, MD

Role: primary

Todd Dreitzler, MD

Role: primary

Juan Rodriguez, MD

Role: primary

Dena Petersen, MD

Role: primary

Ronald P. Karlsberg, MD

Role: primary

Michael Levine, MD

Role: primary

Rami Shaarawy

Role: primary

Milind D. Parikh, MD

Role: primary

Pascal Dabel, MD

Role: primary

Philip Kim, MD

Role: primary

John F. Feller, MD

Role: primary

Pamela Dewar-DeSilva, MD

Role: primary

Ashley Duzik, MD

Role: primary

Yu-Hsiang Sam Lee, MD

Role: primary

Thuong Vo, MD

Role: primary

Richard Park, MD

Role: primary

Nana Barseghian, MD

Role: primary

William Y. Josephson, MD

Role: primary

Sabreen S. Faqihi, MD

Role: primary

Sandra Tsai, MD

Role: primary

Shriram Nallamshetty, MD

Role: primary

Farid Yasharpour, MD

Role: primary

Harpreet Singh, MD

Role: primary

Suvasini Lakshmanan, MD

Role: primary

Dennis Lewis, MD

Role: primary

Steve Simon

Role: primary

Christopher Angus, MD

Role: primary

David Funt, MD

Role: primary

Tamir Salmani, MD

Role: primary

Riquel Gonzalez, MD

Role: primary

Luis Ortega Paz, MD

Role: primary

Osvaldo Caroma, MD

Role: primary

Julie Cadet-Plassman, MD

Role: primary

Teresa B. Alfonso, MD

Role: primary

Alfonso

Role: backup

Leyvi Alvarado Miranda, MD

Role: primary

Jonathan Fialkow, MD

Role: primary

Alba Obourke, MD

Role: primary

Sander Fernandez, MD

Role: primary

Christopher A. Fayeghi, MD

Role: primary

Lauren J. Stipp, MD

Role: primary

Howard S. Koch, MD

Role: primary

Shone Almeida, MD

Role: primary

Alain Domkam, MD

Role: primary

Ambar Kulshreshtha, MD

Role: primary

Karan Raghavan, MD

Role: primary

Claire K. Willie, MD

Role: primary

Thomas G. Moriarity, MD

Role: primary

David A. Hinchman, MD

Role: primary

Amit K. Pursnani, MD

Role: primary

Arshad P. Malik

Role: primary

Ryan P Daly, MD

Role: primary

Enrico L. Martin, MD

Role: primary

Erica Pivato, MD

Role: primary

Shahab Ghafghazi, MD

Role: primary

Sara Collins, MD

Role: primary

Pradeep Natarajan, MD

Role: primary

Ron Blankstein, MD

Role: primary

Cori E Russell, MD

Role: primary

Ahmad Mizyed, MD

Role: primary

Michael D. Miedema, MD

Role: primary

Farhan M. Katchi, MD

Role: primary

Gil Vardi, MD

Role: primary

Justin Buls, MD

Role: primary

Audrey Remmers, MD

Role: primary

Natraj Katta, MD

Role: primary

Tatiana O. Tsvetkova, MD

Role: primary

Bharat R. Mocherla, MD

Role: primary

Andrey Espinoza, MD

Role: primary

Mark T. Finch, MD

Role: primary

Sabahat Bokhari, MD

Role: primary

Himanshu Gupta, MD

Role: primary

Jaffar Raza, MD

Role: primary

Nelly Cohen, MD

Role: primary

Manoj Dalmia, MD

Role: primary

Ammara Mushtaq, MD

Role: primary

Steven Goldberg, MD

Role: primary

Margaret Andersen, MD

Role: primary

Waqas A Malick, MD

Role: primary

Solomon Bienstock, MD

Role: primary

Matthew Cavender, MD

Role: primary

William Yancy, MD

Role: primary

Nafisa Saleem, MD

Role: primary

Patrick J. Morgante, MD

Role: primary

Michael Shapiro, MD

Role: primary

David J. Clardy, MD

Role: primary

Wissam Alajaji, MD

Role: primary

Faisal Latif, MD

Role: primary

Joseph Grillo, MD

Role: primary

Michael Megaly, MD

Role: primary

Venkatesh Nadar, MD

Role: primary

Marc-Andre Cornier, MD

Role: primary

Carlton Volberg, MD

Role: primary

Kashif A. Shaikh, MD

Role: primary

David Huneycutt, MD

Role: primary

Ren Zhang, MD

Role: primary

John T Fowler, MD

Role: primary

Marc Demyun, MD

Role: primary

Ijeoma A. Ekeruo

Role: primary

Rohan R Wagle, MD

Role: primary

Sadeer Al-Kindi, MD

Role: primary

Anjani Pandya, MD

Role: primary

Amando Garza, MD

Role: primary

Moiz M. Shafiq, MD

Role: primary

Muhammad Akram Khan, MD

Role: primary

Salma Saiger, MD

Role: primary

Alan Lee, MD

Role: primary

Benjamin Marcum, MD

Role: primary

Michael Arcarese, MD

Role: primary

Sarah Rinehart, MD

Role: primary

References

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Tsao CW, Aday AW, Almarzooq ZI, Alonso A, Beaton AZ, Bittencourt MS, Boehme AK, Buxton AE, Carson AP, Commodore-Mensah Y, Elkind MSV, Evenson KR, Eze-Nliam C, Ferguson JF, Generoso G, Ho JE, Kalani R, Khan SS, Kissela BM, Knutson KL, Levine DA, Lewis TT, Liu J, Loop MS, Ma J, Mussolino ME, Navaneethan SD, Perak AM, Poudel R, Rezk-Hanna M, Roth GA, Schroeder EB, Shah SH, Thacker EL, VanWagner LB, Virani SS, Voecks JH, Wang NY, Yaffe K, Martin SS. Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association. Circulation. 2022 Feb 22;145(8):e153-e639. doi: 10.1161/CIR.0000000000001052. Epub 2022 Jan 26.

Reference Type BACKGROUND
PMID: 35078371 (View on PubMed)

Clerc OF, Fuchs TA, Stehli J, Benz DC, Grani C, Messerli M, Giannopoulos AA, Buechel RR, Luscher TF, Pazhenkottil AP, Kaufmann PA, Gaemperli O. Non-invasive screening for coronary artery disease in asymptomatic diabetic patients: a systematic review and meta-analysis of randomised controlled trials. Eur Heart J Cardiovasc Imaging. 2018 Aug 1;19(8):838-846. doi: 10.1093/ehjci/jey014.

Reference Type BACKGROUND
PMID: 29452348 (View on PubMed)

Related Links

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http://www.who.int/health-topics/cardiovascular-diseases#tab=tab_1

World Health Organization - Cardiovascular Diseases

Other Identifiers

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202302CPC

Identifier Type: -

Identifier Source: org_study_id