Long-term effects of angiotensin receptor neprilysin inhibitor therapy in heart failure patients with reduced ejection fraction: A retrospective cohort study

Medicine (Baltimore). 2023 Oct 27;102(43):e35589. doi: 10.1097/MD.0000000000035589.

Abstract

Heart failure is an increasing public health issue with substantial morbidity and mortality rates. This study aimed to evaluate the efficacy, safety, and long-term outcomes of angiotensin receptor neprilysin inhibitor (ARNi) in the treatment of heart failure with reduced ejection fraction (HFrEF) 5 years after treatment initiation. This retrospective study analyzed a cohort of 75 patients diagnosed with HFrEF over a period of 5 years after the initiation of ARNi therapy. The initial clinical condition, laboratory and echocardiographic measurements including left ventricular ejection fraction (LVEF), New York Heart Association functional classes (NYHA-FC) and the prognostic nutritional index were compared to the corresponding values obtained after a 5-year period of ARNi therapy. In addition, the number of annual hospitalizations, mortality rates and any history of adverse effects during the follow-up period were recorded. The N-terminal pro-brain natriuretic peptide (NT-proBNP) level, LVEF, and NYHA-FC values demonstrated significant improvement at the end of the 5-year follow-up period (all parameters, P < .001). Although the observed increase in the prognostic nutritional index was not statistically significant (P = .077), it is worth noting. A significant reduction in daily diuretic doses and hospitalizations due to heart failure was observed following the use of ARNi (all comparisons, P < .001). The prevalence of hypotension was around 16% (being symptomatic in 4%), making it the most frequently observed adverse event. The 5-year cardiovascular mortality rate was 17.3%. The use of ARNi in HFrEF patients was associated with a notable improvement in NYHA-FC, LVEF, and NT-proBNP levels in the long-term, while also leading to a better nutritional status and reduced need for diuretics and annual hospitalization. Additionally, ARNi usage has been associated with improved nutritional status, decreased reliance on diuretics, and reduced frequency of annual hospitalizations. These effects were associated with a lack of significant increase in adverse effects. These results may contribute to a better understanding of ARNi's long-term effects on patient outcomes.

MeSH terms

  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin Receptor Antagonists / therapeutic use
  • Antihypertensive Agents / therapeutic use
  • Biphenyl Compounds / therapeutic use
  • Diuretics / therapeutic use
  • Drug Combinations
  • Heart Failure*
  • Humans
  • Neprilysin
  • Retrospective Studies
  • Stroke Volume
  • Treatment Outcome
  • Valsartan / therapeutic use
  • Ventricular Function, Left

Substances

  • Valsartan
  • Neprilysin
  • Antihypertensive Agents
  • Diuretics
  • Angiotensin Receptor Antagonists
  • Drug Combinations
  • Biphenyl Compounds