Effect of sacubitril/valsartan on cardiac remodeling compared with other renin-angiotensin system inhibitors: a difference-in-difference analysis of propensity-score matched samples

Clin Res Cardiol. 2024 Jun;113(6):856-865. doi: 10.1007/s00392-023-02306-0. Epub 2023 Sep 21.

Abstract

Background: In patients with heart failure with reduced ejection fraction (HFrEF), treatment with sacubitril-valsartan (S/V) may reverse left ventricular remodeling (rLVR). Whether this effect is superior to that induced by other renin-angiotensin system (RAS) inhibitors is not well known.

Methods: HFrEF patients treated with S/V (n = 795) were compared, by propensity score matching, with a historical cohort of 831 HFrEF patients (non-S/V group) treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (RAS inhibitors). All patients were also treated with beta-blockers and shared the same protocol with repeat echocardiogram 8-12 months after starting therapy. The difference-in-difference (DiD) analysis was used to evaluate the impact of S/V on CR indices between the two groups.

Results: After propensity score matching, compared to non-S/V group (n = 354), S/V group (n = 354) showed a relative greater reduction in end-diastolic and end-systolic volume index (ESVI), and greater increase in ejection fraction (DiD estimator = + 5.42 mL/m2, P = 0.0005; + 4.68 mL/m2, P = 0.0009, and + 1.76%, P = 0.002, respectively). Reverse LVR (reduction in ESVI ≥ 15% from baseline) was more prevalent in S/V than in non-S/V group (34% vs 26%, P = 0.017), while adverse LVR (aLVR, increase in ESVI at follow-up ≥ 15%) was more frequent in non-S/V than in S/V (16% vs 7%, P < 0.001). The beneficial effect of S/V on CR over other RAS inhibitors was appreciable across a wide range of patient's age and baseline end-diastolic volume index, but it tended to attenuate in more dilated left ventricles (P for interaction = NS for both).

Conclusion: In HFrEF patients treated with beta-blockers, sacubitril/valsartan is associated with a relative greater benefit in LV reverse remodeling indices than other RAS inhibitors.

Keywords: ARNI; Cardiac remodeling; Heart failure, RAS inhibitors; Neprilysin inhibitors; Sacubitril/valsartan.

Publication types

  • Comparative Study

MeSH terms

  • Aminobutyrates* / therapeutic use
  • Angiotensin Receptor Antagonists* / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Biphenyl Compounds*
  • Drug Combinations*
  • Echocardiography
  • Female
  • Heart Failure* / drug therapy
  • Heart Failure* / physiopathology
  • Humans
  • Male
  • Propensity Score*
  • Renin-Angiotensin System / drug effects
  • Retrospective Studies
  • Stroke Volume* / drug effects
  • Stroke Volume* / physiology
  • Tetrazoles* / therapeutic use
  • Treatment Outcome
  • Valsartan* / therapeutic use
  • Ventricular Function, Left / drug effects
  • Ventricular Function, Left / physiology
  • Ventricular Remodeling* / drug effects

Substances

  • Aminobutyrates
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Biphenyl Compounds
  • Drug Combinations
  • sacubitril and valsartan sodium hydrate drug combination
  • Tetrazoles
  • Valsartan
  • sacubitril