Heart failure (HF) is a public health challenge with high morbidity and mortality risk, and societal economic costs. The lifetime risk of developing HF stands at one in four. A significant portion of the population already resides in precursor stages, with roughly two-third of adults in the United States classified as either Stage A (at risk) or Stage B (pre-HF). Despite advances in drugs and device-based therapies, once HF develops, these patients remain at an unacceptably high risk for mortality, morbidity, and adverse health status, underscoring the need for focus on primary prevention of HF. The prevention of atherosclerotic cardiovascular disease is supported by established guidelines with clear targets and pharmacotherapies with specific labels for prevention. However, prevention of HF remains less well established. No therapeutic agent is approved yet specifically for the primary prevention of HF. Defining and adjudicating incident HF is challenging. Most trials report initial HF hospitalizations only. Conventional hospitalization-based definition of incident HF does not take into account outpatient settings where most HF is diagnosed. A fundamental re-evaluation of preventive strategies for HF is required, moving incrementally from coronary disease-based approaches to more global populations as many HF cases arise from non-atherosclerotic causes, such as obesity, hypertension, cancer therapies, and the cardio-kidney-metabolic syndrome. This review addresses practical challenges in defining incident HF, trial duration, and regulatory pathways, while summarizing the landscape of current and ongoing prevention trials, identifying evidence gaps, and highlighting future priorities.
Editors
Editor-in-Chief
Harlan M. Krumholz, MD, SM, FACC
CME Editor
Ragavendra R. Baliga, MD
Author
Javed Butler, MD, MPH, MDA
Important Dates
Date of Release: April 21, 2026
Term of Approval/Date of CME/MOC Expiration: April 20, 2027