Developing New Treatments for Heart Failure: Focus on the Heart

Area of Science:

• Cardiology
• Pharmacology
• Translational Medicine

Background:

• Significant advancements in heart failure (HF) therapy for reduced ejection fraction (HFrEF) exist, primarily through neurohormonal pathway blockade.
• However, recent decades show a decline in successful HF drug development, with many novel agents failing due to lack of incremental benefit or safety concerns like hypotension.
• Crucially, no specific therapies are approved for HF with preserved ejection fraction (HFpEF) or for worsening chronic HF, including acute decompensated HF.

Framework:

• A critical disconnect exists between basic science discovery, early drug development, and pivotal clinical trials, evidenced by promising Phase II results often not translating to successful Phase III outcomes.
• A major unmet need is identifying homogeneous patient subsets with specific underlying disease mechanisms amenable to targeted therapies.
• Future drug development should consider therapies facilitating reverse remodeling by directly targeting cardiac mechanisms, moving beyond solely unloading the heart or targeting systemic neurohormones.

Implementation:

• Advancements in cardiac imaging offer potential for earlier, more focused assessment of drug effects directly on the heart during development.
• A 2015 FDA-facilitated meeting convened experts to discuss challenges and strategies for successful HF drug development.
• Key takeaway dialogue from this meeting is summarized to guide future research and development efforts.

Implications:

• Addressing the translational gap and unmet needs in HF drug development is crucial for future therapeutic success.
• Developing targeted therapies for specific HF patient subsets, including HFpEF and worsening chronic HF, is a priority.
• Integrating advanced imaging and novel drug development strategies holds promise for more effective HF treatments.