Skip to content

Lee V, et al. Effects of sacubitril/valsartan on hypertensive heart disease: the REVERSE-LVH randomized phase 2 trial. Nat Commun. 2025;16:6981. PMID 40739095

One-paragraph summary

REVERSE-LVH randomized 78 adults with hypertension and CMR-confirmed LVH to sacubitril/valsartan or valsartan. At 52 weeks, with similar ambulatory systolic BP, CMR interstitial fibrosis volume fell by −5.2±5.4 versus −2.5±3.1 mL (P=0.006). Several secondary remodeling measures also favored sacubitril/valsartan. The trial is a proof-of-concept that myocardial tissue change may differ despite similar peripheral BP, but its small phase 2 design and surrogate primary outcome do not establish prevention of HF, arrhythmia, stroke, or death.

Design

Element Detail
Registration NCT03553810
Population 78 adults with hypertension and CMR-LVH
Intervention Sacubitril/valsartan
Comparator Valsartan
Duration 52 weeks
Primary endpoint CMR interstitial fibrosis volume

Key findings

  • Interstitial volume change: −5.2±5.4 versus −2.5±3.1 mL; P=0.006.
  • Ambulatory systolic BP was similar at 52 weeks, supporting but not proving a BP-independent remodeling effect.
  • The study separated extracellular-volume fraction from absolute interstitial volume, an important distinction when cell mass also changes.
  • Secondary structural and functional findings provide a coherent signal but remain exploratory.
  • Protocol details were published earlier (PMID 37674806).

Limitations

  • Small sample and open-label treatment.
  • Phase 2 surrogate-endpoint design; no power for clinical events.
  • Multiple secondary endpoints increase false-positive risk.
  • Generalizability across ancestry, CKD, obesity, and different CMR platforms requires study.
  • Similar measured ambulatory SBP does not exclude every hemodynamic difference.

Why it matters

REVERSE-LVH is the clearest recent experiment aimed at myocardial biology inside HHD rather than BP alone. It justifies a larger endpoint trial and biomarker-validation program; it does not justify routine ARNI use solely to regress uncomplicated hypertensive LVH.

Cited by wiki pages

  • overview
  • ventricular remodeling
  • diastolic dysfunction and HFpEF
  • biomarkers and imaging markers
  • pharmacologic prevention and regression
  • heart-failure management
  • clinical-trials landscape