Early Treatment in High Lifetime Risk of Cardiovascular Diseases: What Prevention Trials are Feasible and Could Change Clinical Practice?

The National Heart, Lung, and Blood Institute (NHLBI) convened a multidisciplinary workshop on possible prevention trials to reduce cardiovascular disease (CVD) risk in adults with a relative low ten-year risk of CVD yet high lifetime CVD risk. Experts reviewed relevant guidelines, summarized the state of the evidence, and explored the design of feasible clinical trials with the potential to change practice—particularly, ways to identify the appropriate cohort, possible interventions, incorporation of treatment strategies to address health disparities, and outcome assessment.

Background

Many young adults and middle-aged adults have short-term (≤10-year) risks for CVD of less than 10 percent but a much higher lifetime risk. For many CVD risk factors, such as LDL cholesterol and systolic blood pressure, an important question is: Are there demonstrated large benefits associated with earlier, more rigorous, and effective treatment of CVD risk factors in the prevention of CVD events?

Workshop Purpose and Objectives

The objectives of the workshop were to:

• Review the American Heart Association/American College of Cardiology recent guidelines on hypertension (2017), blood cholesterol (2018), and primary prevention of cardiovascular disease (2019) to identify the research gaps for subpopulations with low 10-year CVD risks but high lifetime risk.
• Evaluate key considerations for designing feasible and potentially practice-changing trials of interventions that might substantially improve CVD prevention in young and middle-aged adults with high lifetime risk.

Concise Summary of Discussions

Presentations and discussions were centered around the following areas.

• State of the evidence on risk factor interventions among individuals with low 10-year but high lifetime risk.
• Identifying the ‘right” cohort – risk assessment and its impact on the size of the trial eligible population.
• Possible lifestyle, behavioral, and pharmacological interventions to be evaluated in trials.
• Considerations for successful implementation of prevention trials and/or treatment strategies for health disparity populations and/or in safety net health care systems.
• Possible trial endpoints, ranging from major adverse cardiovascular events (MACE) to possible surrogate outcomes.
• Feasibility of practice-changing prevention trials in young or middle-aged adults with low ten-year risk.

Summary of the potential approaches and research opportunities discussed:

• More than 50% of the adult population has low short-term risk but high lifetime risk for CVD based on contemporary risk equations.
• Use of coronary calcium scores, polygenetic risk scores, and other measures of subclinical disease may be useful in identifying the population with higher short-term and lifetime risk.
• Enhanced recruitment strategies involving more intense community engagement is a key factor to obtaining a trial population that is racially, ethnically, geographically, and socially diverse.
• Several interventions appear to be promising, ranging from focusing on large reductions in a single cardiovascular risk factor to multiple risk factor interventions.
• Pharmacological interventions discussed include generic, non-generic, and investigational drugs.
• Preliminary discussions suggested that some of the discussed trial designs were feasible.
• In addition to evaluating interventions, trials might make broader contributions to the science of prevention of CVD.

Workshop Report

Navar AM, Fine LJ, Ambrosius WT, Brown A, Douglas PS, Johnson K, Khera AV, Lloyd-Jones D, Michos ED, Mujahid M, Muñoz D, Nasir K, Redmond N, Ridker PM, Robinson J, Schopfer D, Tate DF, Lewis CE. Earlier treatment in adults with high lifetime risk of cardiovascular diseases: What prevention trials are feasible and could change clinical practice? Report of a National Heart, Lung, and Blood Institute (NHLBI) Workshop. Am J Prev Cardiol. 2022 Nov 13;12:100430. doi: 10.1016/j.ajpc.2022.100430. PMID: 36439649; PMCID: PMC9691440.

NHLBI Contact

Lawrence Fine, MD, DrPH
Division of Cardiovascular Sciences, NHLBI
Lawrence.Fine@nih.gov

Co-chairs

Cora E. (Beth) Lewis MD MSPH, Chair, Department of Epidemiology, School of Public Health, University of Alabama at Birmingham

Ann Marie Navar, MD PhD, Associate Professor, Departments of Internal Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center

NHLBI Organizing Committee

Lawrence Fine, MD, DrPH
Nicole Redmond, MD, PhD, MPH
David Schopfer, MD, MAS

Workshop Speakers/Moderators

Walter T. Ambrosius, PhD
Wake Forest University

Cheryl Anderson, PhD
University of California at San Diego

Arleen Brown, MD, PhD
University of California at Los Angeles

Pamela Douglas, MD
Duke University

David C. Goff, Jr., MD, PhD
NHLBI

Karen Johnson, MD, PhD
University of Tennessee

Amit V. Khera, MD, MSc
Harvard University

Donald Lloyd-Jones, MD, ScM
Northwestern University

Erin Michos, MD, MHS
Johns Hopkins University

Mahasin Mujahid, PhD, MS
University of California at Berkeley

Daniel Muñoz, MD, MPA
Vanderbilt University

Khurram Nasir, MD, MPH
Houston Methodist

Paul Ridker, MD, MPH
Harvard University

Jennifer Robinson, MD, MPH
University of Iowa

Deborah F. Tate, PhD
University of North Carolina