Pharmacogenomics of angiotensin receptor/neprilysin inhibitor and its long‐term side effects. Issue 4 (14th July 2017)

• Record Type: Journal Article
• Authors: Krittanawong, Chayakrit; Kitai, Takeshi
• Is Part Of: Cardiovascular therapeutics. Volume 35:Issue 4(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-07-14
• Subjects: Alzheimer's disease -- Angiotensin receptor‐neprilysin inhibitor -- Heart failure -- Heart failure with preserved ejection fraction -- Heart failure with reduced ejection fraction -- Omapatrilat; Cardiovascular pharmacology -- Periodicals; Cardiovascular agents -- Periodicals; Cardiovascular system -- Diseases -- Chemotherapy -- Periodicals; Cardiovascular Agents -- Periodicals; Cardiovascular Diseases -- drug therapy -- Periodicals; Agents cardiovasculaires -- Périodiques; Appareil cardiovasculaire -- Maladies -- Chimiothérapie -- Périodiques; 616.1005
• DOI: 10.1111/1755-5922.12272
• Languages: English
• ISSNs: 1755-5914

Abstract

Summary: The development of the promising agent sacubitril/valsartan, known as an angiotensin receptor blocker‐neprilysin inhibitor (ARNI), to improve heart failure (HF) management, may benefit morbidity, mortality, and readmission rates in patients with HF. The PARADIGM‐HF trial demonstrated that the ARNI can reduce morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), while ongoing PARAMOUNT and PARAGON‐HF trials determined whether the ARNI has morbidity and mortality benefits in patients with heart failure with preserved ejection fraction (HFpEF). However, the risk of long‐term side effects of the ARNI such as cognitive dysfunction or Alzheimer's disease (AD) remains unknown. In fact, neprilysin (NEP), encoded by NEP or MME gene, is a principal peptidase involved in the degradation of β‐amyloid (Aβ) protein. Several studies have demonstrated that polymorphisms of the NEP gene may be associated with AD and cerebral amyloid angiopathy (CAA). Pharmacogenomics, the study of variability in drug response due to genetic polymorphisms, can potentially explain the variability in the effect of the ARNI and their side effects. Therefore, we have attempted to highlight pharmacogenomic factors and potential long‐term side effects of the ARNI. Physicians should carefully monitor elderly patients with genetic risk factors for AD and CAA. In the future, genetic testing and genomic testing for NEP polymorphisms may play an important role in monitoring long‐term side effects in ARNI‐treated HF patients.