Effects of Angiotensin Receptor-Neprilysin Inhibitors Versus Enalapril or Valsartan on Patients With Heart Failure: A Systematic Review and Meta-Analysis

Arpit Jain; Shourya Meyur; Lovish Wadhwa; Kamaldeep Singh; Rishi Sharma; Ishita Panchal; Giustino Varrassi

doi:10.7759/cureus.41566

Effects of Angiotensin Receptor-Neprilysin Inhibitors Versus Enalapril or Valsartan on Patients With Heart Failure: A Systematic Review and Meta-Analysis

Cureus. 2023 Jul 8;15(7):e41566. doi: 10.7759/cureus.41566. eCollection 2023 Jul.

Authors

Arpit Jain¹, Shourya Meyur^{2

3}, Lovish Wadhwa⁴, Kamaldeep Singh^{5

6}, Rishi Sharma⁷, Ishita Panchal⁸, Giustino Varrassi⁹

Affiliations

¹ Emergency Medicine, All India Institute of Medical Sciences, New Delhi, New Delhi, IND.
² Medicine, AMA School of Medicine, Makati, PHL.
³ Internal Medicine, Sambhunath Pandit Hospital, Kolkata, IND.
⁴ Medicine, Ramaiah Medical College, Bangalore, IND.
⁵ Cardiology, Government Medical College & Hospital, Chandigarh, IND.
⁶ Internal Medicine, Jawaharlal Nehru Medical College, Chandigarh, IND.
⁷ Medicine, D. Y. Patil Medical College, D. Y. Patil Education Society Deemed University, Kolhapur, IND.
⁸ Internal Medicine, Jawaharlal Nehru Medical College, Belagavi, IND.
⁹ Pain Medicine, Paolo Procacci Foundation, Rome, ITA.

Abstract

Recent studies have focused on treating heart failure, primarily mitigating symptoms and reducing the risk of mortality and other cardiovascular complications. A promising new treatment approach involves using LCZ696, an angiotensin receptor-neprilysin inhibitor (ARNI) comprising sacubitril and valsartan. This treatment is superior to the conventional drugs enalapril or valsartan in patients diagnosed with heart failure. A systematic search was conducted on PubMed, the Cochrane Library, and Elsevier's ScienceDirect databases to identify studies comparing sacubitril/valsartan with other drugs in heart failure patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). The analyses were conducted using the random-effects model. The study's primary outcomes included all-cause mortality, death from cardiovascular causes, first hospitalization for heart failure, congestive heart failure, and changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical score. The pooled analysis showed that treatment with the sacubitril/valsartan combination was associated with a significantly decreased rate of first hospitalization for heart failure (RR: 0.86; 95% CI: 0.79, 0.98, p: 0.03; I2: 57%) and significantly increased KCCQ clinical score (WMD: 2.20; 95% CI: 0.33, 4.06, p: 0.02; I2: 100%). However, the two groups had no significant difference in all-cause mortality (RR: 0.90; 95% CI: 0.80, 1.01, p: 0.08; I2: 20%), death from cardiovascular causes (RR: 0.96; 95% CI: 0.87, 1.05, p: 0.34; I2: 0%), or congestive heart failure (RR: 0.97; 95% CI: 0.75, 1.25, p: 0.19; I2: 38%). The research findings suggest that sacubitril/valsartan (LCZ696) reduces hospitalizations due to heart failure and improves KCCQ clinical scores. This treatment also reduces the decline in renal function and side effects associated with enalapril or valsartan. Nonetheless, further high-quality randomized controlled trials with large sample sizes are needed to assess other impacts of this therapy on heart failure patients. Overall, the use of LCZ696 represents a promising new approach to the treatment of heart failure.

Keywords: angiotensin receptor–neprilysin inhibitors; arni; enalapril; heart failure; meta-analysis; sacubitril/valsartan; systematic review; valsartan.

Publication types

Review