Galectin-3 predicts response to statin therapy in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA)

Eur Heart J. 2012 Sep;33(18):2290-6. doi: 10.1093/eurheartj/ehs077. Epub 2012 Apr 17.

Abstract

Aims: To investigate whether plasma galectin-3, a mediator of fibrogenesis, can identify patients with chronic heart failure (HF) for whom statins are effective.

Methods and results: Patients with ischaemic systolic HF enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) were randomly assigned to 10 mg/day of rosuvastatin or placebo. Galectin-3 was measured in plasma. The primary outcome was cardiovascular death, myocardial infarction, or stroke. Of 1492 patients, 411 had a primary event during a median follow-up of 32.8 months. There was an interaction between baseline galectin-3 and rosuvastatin on the primary endpoint (P-value for interaction = 0.036). Among patients with below the median plasma concentrations of galectin-3 (≤ 19.0 ng/mL), those assigned to rosuvastatin had a lower primary event rate [hazard ratio (HR) 0.65; 95% confidence interval (CI), 0.46-0.92; P= 0.014], lower total mortality (HR 0.70; 95% CI, 0.50-0.98; P= 0.038), and lower event rate of all-cause mortality and HF hospitalizations (HR 0.72; 95% CI, 0.54-0.98; P= 0.017) compared with placebo, but no benefit was observed in patients with higher levels of galectin-3. The combination of concurrently low concentrations of galectin-3 and N-terminal pro-B-type natriuretic peptide (<102.7 pmol/L) identified patients with a large benefit with rosuvastatin (HR 0.33; 95% CI, 0.16-0.67; P= 0.002).

Conclusion: Patients with systolic HF of ischaemic aetiology who have galectin-3 values <19.0 ng/mL may benefit from rosuvastatin treatment. However, the data from this post hoc analysis should be interpreted with caution since the overall results of the CORONA study did not show a significant effect on the primary endpoint.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Female
  • Fluorobenzenes / therapeutic use*
  • Galectin 3 / blood*
  • Heart Failure, Systolic / blood
  • Heart Failure, Systolic / drug therapy*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Kaplan-Meier Estimate
  • Lipid Metabolism / drug effects
  • Male
  • Myocardial Infarction / etiology
  • Natriuretic Peptide, Brain / metabolism
  • Peptide Fragments / metabolism
  • Pyrimidines / therapeutic use*
  • Rosuvastatin Calcium
  • Stroke / etiology
  • Sulfonamides / therapeutic use*
  • Treatment Outcome

Substances

  • Biomarkers
  • Fluorobenzenes
  • Galectin 3
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Peptide Fragments
  • Pyrimidines
  • Sulfonamides
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Rosuvastatin Calcium
  • C-Reactive Protein