Real-world utilisation of angiotensin-neprilysin inhibitors in older adults with heart failure.

Over the last decade, treatment for heart failure with reduced ejection fraction (HFrEF) has advanced, with the incremental addition of novel evidence-based medical therapies. The landmark PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) study showed that the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan was superior to enalapril in reducing risk of death and HF hospitalisations.1 This has paved the way for rapid incorporation of ARNI into the treatment guidelines for HFrEF, with additional indications on the horizon. We are now in an era of quadruple therapy that incorporates an optimal combination of beta-blockers, ACE inhibitors (ACEi)/angiotensin receptor blockers (ARB)/ARNI, mineralocorticoid receptor antagonists (MRA) and sodium/glucose cotransporter-2 inhibitors (SGLT2i) for chronic HFrEF.2 In this issue of Heart , Dr Desai and colleagues evaluate the real-world utilisation of ARNI in HFrEF patients age ≥65 years using the Medicare database (2014–2017).3 Case ascertainment of HF was based on International Classification of Diseases (ICD) codes, with further stratification dependent on a validated claims-based algorithm and/or ARNI initiation to limit the reference group to those with HFrEF. While there may be some degree of misclassification, the recently expanded US Food and Drug Administration indication for ARNI based on post hoc analysis of PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with preserved EF) would suggest that those with HFpEF at the lower end of the ‘normal’ EF spectrum may derive similar benefit to those with HFrEF. Hence, ARNI is now indicated in patients with chronic HF regardless of EF.4 In the current manuscript, separate subcohorts were created from the HFrEF population with an ‘initiator’ group (newly starting ARNI or ACEi/ARB who were previously naive to these medications) and a ‘switcher’ group (switching from …