Heart Failure Prevention: Evidence Generation, Trial Design, and Regulatory Pathways.

Area of Science:

• Cardiology
• Public Health
• Preventive Medicine

Background:

• Heart failure (HF) poses a significant public health burden with high morbidity, mortality, and economic costs.
• A substantial portion of the adult population (two-thirds in the US) is in pre-HF stages (Stage A or B).
• Existing therapies improve outcomes post-HF diagnosis but fail to adequately reduce mortality and morbidity, highlighting the need for primary HF prevention.

Purpose of the Study:

• To address the challenges in defining and preventing incident heart failure.
• To reevaluate preventive strategies beyond atherosclerotic cardiovascular disease.
• To summarize current and ongoing HF prevention trials and identify future research priorities.

Main Methods:

• Review of current literature on HF definition and prevention strategies.
• Analysis of challenges in clinical trial design, duration, and regulatory pathways for HF prevention.
• Synthesis of data from ongoing and completed HF prevention trials.

Main Results:

• No therapeutic agent is currently approved specifically for primary HF prevention.
• Defining and adjudicating incident HF is complex, with most trials relying on hospitalization data, neglecting outpatient diagnoses.
• HF arises from diverse causes beyond atherosclerosis, including obesity, hypertension, and cancer therapies.

Conclusions:

• A fundamental reevaluation of HF prevention strategies is necessary, expanding beyond coronary disease-focused approaches.
• Future prevention efforts must consider a broader range of HF etiologies and incorporate outpatient diagnostic settings.
• Addressing evidence gaps and refining regulatory pathways are critical for advancing primary HF prevention.