Efficacy and Safety of LCZ696 for Short-term Management of Essential Hypertension Compared With ARBs: A Meta-analysis of Randomized Controlled Trials

J Cardiovasc Pharmacol. 2021 May 1;77(5):650-659. doi: 10.1097/FJC.0000000000001001.

Abstract

Whether LCZ696 (neprilysin inhibitor + valsartan) has greater advantages of blood pressure (BP) lowering than angiotensin II type 1 receptor blockers (ARBs) is unclear. To provide more detailed information about the benefits of LCZ696, we conducted a meta-analysis to evaluate the efficacy and safety of LCZ696 for short-term management of hypertension compared with ARBs. We searched PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov, using relevant keywords. We used a random or fixed effects model to calculate the weighted mean difference (WMD) of changes in BP and the risk ratio (RR) for BP control rates and adverse events (AEs). In this meta-analysis, 9 studies were incorporated. Compared with ARBs, LCZ696 revealed a significant reduction in mean sitting systolic BP [msSBP; WMD -4.79 mm Hg; 95% confidence interval (CI): -5.46 to -4.11 mm Hg], mean sitting diastolic BP (msDBP; WMD -2.12 mm Hg; 95% CI: -2.53 to -1.71 mm Hg), mean sitting pulse pressure (msPP; WMD -2.79 mm Hg; 95% CI: -3.52 to -2.07 mm Hg), and mean ambulatory pulse pressure (maPP; WMD -2.96 mm Hg; 95% CI: -3.35 to -2.57 mm Hg). LCZ696 had a higher BP control rate than ARBs (OR = 1.55; 95% CI: 1.39 to 1.73). There was no significant difference between LCZ696 and ARBs in the incidence of AEs (RR = 1.10; 95% CI: 0.96 to 1.25) and discontinuations because of AEs (RR = 0.97; 95% CI: 0.54 to 1.32). Overall, in short-term treatment, LCZ696 has greater advantages of antihypertensive efficacy and the safety is not inferior to ARBs. Further long-term studies are required to rule out the potential risks of beta amyloid accumulation and the potential for Alzheimer's disease.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aminobutyrates / adverse effects
  • Aminobutyrates / therapeutic use*
  • Angiotensin Receptor Antagonists / adverse effects
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Biphenyl Compounds / adverse effects
  • Biphenyl Compounds / therapeutic use*
  • Blood Pressure / drug effects*
  • Drug Combinations
  • Essential Hypertension / diagnosis
  • Essential Hypertension / drug therapy*
  • Essential Hypertension / physiopathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neprilysin / antagonists & inhibitors
  • Protease Inhibitors / adverse effects
  • Protease Inhibitors / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Valsartan / adverse effects
  • Valsartan / therapeutic use*
  • Young Adult

Substances

  • Aminobutyrates
  • Angiotensin Receptor Antagonists
  • Biphenyl Compounds
  • Drug Combinations
  • Protease Inhibitors
  • Valsartan
  • Neprilysin
  • sacubitril and valsartan sodium hydrate drug combination