Pharmacogenomics of angiotensin receptor/neprilysin inhibitor and its long-term side effects

Area of Science:

• Pharmacogenomics and Cardiovascular Medicine
• Neurodegenerative Disease Research

Background:

• Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), shows promise in managing heart failure (HF).
• Clinical trials like PARADIGM-HF, PARAMOUNT, and PARAGON-HF investigate ARNI's benefits in heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF).
• Potential long-term side effects of ARNI, including cognitive dysfunction and Alzheimer's disease (AD), are not fully understood.

Purpose of the Study:

• To explore the pharmacogenomic factors influencing ARNI efficacy and side effects.
• To highlight potential long-term risks associated with ARNI therapy, particularly concerning neurodegenerative diseases.
• To emphasize the role of genetic variations in neprilysin (NEP) in AD and cerebral amyloid angiopathy (CAA).

Main Methods:

• Review of existing literature on ARNI, heart failure management, and neprilysin function.
• Analysis of studies linking NEP gene polymorphisms to Alzheimer's disease and cerebral amyloid angiopathy.
• Discussion of pharmacogenomic principles in understanding drug response variability.

Main Results:

• Neprilysin (NEP) plays a role in degrading β-amyloid (Aβ) protein, a key factor in Alzheimer's disease.
• Polymorphisms in the NEP gene are associated with an increased risk of AD and CAA.
• Pharmacogenomics offers a framework to understand individual variations in ARNI response and side effects.

Conclusions:

• Physicians should consider genetic risk factors for AD and CAA when prescribing ARNI, especially in elderly patients.
• Genetic testing for NEP polymorphisms may become crucial for monitoring long-term ARNI side effects in heart failure patients.
• Further research into pharmacogenomic implications of ARNI is warranted to optimize patient care and minimize risks.