Metoprolol reverses left ventricular remodeling in patients with asymptomatic systolic dysfunction: the REversal of VEntricular Remodeling with Toprol-XL (REVERT) trial

Circulation. 2007 Jul 3;116(1):49-56. doi: 10.1161/CIRCULATIONAHA.106.666016. Epub 2007 Jun 18.

Abstract

Background: There are no randomized, controlled trial data to support the benefit of beta-blockers in patients with asymptomatic left ventricular systolic dysfunction. We investigated whether beta-blocker therapy ameliorates left ventricular remodeling in asymptomatic patients with left ventricular systolic dysfunction.

Method and results: Patients with left ventricular ejection fraction <40%, mild left ventricular dilation, and no symptoms of heart failure (New York Heart Association class I) were randomly assigned to receive extended-release metoprolol succinate (Toprol-XL, AstraZeneca) 200 mg or 50 mg or placebo for 12 months. Echocardiographic assessments of left ventricular end-systolic volume, end-diastolic volume, mass, and ejection fraction were performed at baseline and at 6 and 12 months. The 149 patients randomized to the 3 treatment groups (200 mg, n=48; 50 mg, n=48; and placebo, n=53) were similar with regard to all baseline characteristics including age (mean, 66 years), gender (74% male), plasma brain natriuretic peptide (79 pg/mL), left ventricular end-diastolic volume index (110 mL/m2), and left ventricular ejection fraction (27%). At 12 months in the 200-mg group, there was a 14+/-3 mL/m2 decrease (least square mean+/-SE) in end-systolic volume index and a 6+/-1% increase in left ventricular ejection fraction (P<0.05 versus baseline and placebo for both). The decrease in end-diastolic volume index (14+/-3) was different from that seen at baseline (P<0.05) but not with placebo. In the 50-mg group, end-systolic and end-diastolic volume indexes decreased relative to baseline but were not different from what was seen with placebo, whereas ejection fraction increased by 4+/-1% (P<0.05 versus baseline and placebo).

Conclusion: Beta-blocker therapy can ameliorate left ventricular remodeling in asymptomatic patients with left ventricular systolic dysfunction.

Trial registration: ClinicalTrials.gov NCT00038077.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / therapeutic use*
  • Aged
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Blood Pressure / drug effects
  • Cardiovascular Agents / administration & dosage
  • Cardiovascular Agents / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Heart Rate / drug effects
  • Humans
  • Male
  • Metoprolol / administration & dosage
  • Metoprolol / pharmacology
  • Metoprolol / therapeutic use*
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Stroke Volume
  • Treatment Outcome
  • Ultrasonography
  • Ventricular Dysfunction, Left / blood
  • Ventricular Dysfunction, Left / diagnostic imaging
  • Ventricular Dysfunction, Left / drug therapy*
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Remodeling / drug effects*

Substances

  • Adrenergic beta-Antagonists
  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Cardiovascular Agents
  • Natriuretic Peptide, Brain
  • Metoprolol

Associated data

  • ClinicalTrials.gov/NCT00038077