Drugs' development in acute heart failure: what went wrong?

Area of Science:

• Cardiology
• Pharmacology
• Drug Development

Background:

• Acute heart failure (AHF) presents significant challenges in diagnosis, treatment, and prognosis.
• Despite extensive research, the pharmacological armamentarium for AHF remains limited, with few drug approvals in recent decades.

Purpose of the Study:

• To review drugs developed for AHF since the early 2000s.
• To identify factors contributing to successful drug approvals or program terminations.
• To delineate future trajectories for AHF drug development.

Main Methods:

• Systematic review of published data on AHF drug development programs since the early 2000s.
• Analysis of preclinical and clinical development stages, focusing on endpoint assessment and study design.

Main Results:

• Preclinical limitations include animal models that do not fully replicate human AHF complexity.
• Clinical development is hampered by a disconnect between short-term and long-term endpoints, lack of endpoint standardization, absence of predictive biomarkers, and heterogeneous study populations.
• Inconsistent eligibility criteria, assessment timing, drug schedules, and background therapies further complicate clinical trials.

Conclusions:

• Enhancing the understanding of AHF pathophysiology is essential.
• Successful AHF drug development requires addressing limitations in preclinical models and clinical trial design, including endpoint validation and biomarker use.
• Stronger collaboration among the scientific community, industry, and regulatory agencies is vital for therapeutic innovation in AHF.