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Galectin-3 predicts response to statin therapy in the Controlled Rosuvastatin Multinational Trial in Heart Failure
Lars Gullestad1, Thor Ueland, John Kjekshus
1Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo N-0027, Norway. lars.gullestad@medisin.uio.no
Insights
Plasma galectin-3 levels can identify patients with heart failure (HF) who benefit from rosuvastatin treatment. Those with lower galectin-3 concentrations showed improved outcomes, suggesting a personalized approach to statin therapy in HF.
Area of Science:
- Cardiology
- Biomarkers
- Pharmacogenomics
Background:
- Heart failure (HF) is a complex condition with significant morbidity and mortality.
- Fibrogenesis plays a crucial role in the pathophysiology of HF.
- Galectin-3 is a key mediator of fibrogenesis and a potential biomarker in HF.
Purpose of the Study:
- To determine if plasma galectin-3 levels can predict statin efficacy in patients with chronic systolic heart failure.
- To investigate the interaction between galectin-3 and rosuvastatin treatment in the CORONA trial.
Main Methods:
- Analysis of plasma galectin-3 levels in patients with ischaemic systolic HF from the CORONA trial.
- Random assignment to rosuvastatin or placebo.
- Assessment of cardiovascular death, myocardial infarction, or stroke as the primary endpoint.
Main Results:
- A significant interaction was observed between baseline galectin-3 and rosuvastatin treatment (P=0.036).
- Patients with below-median galectin-3 levels (≤ 19.0 ng/mL) showed reduced primary events, total mortality, and HF hospitalizations with rosuvastatin compared to placebo.
- No significant benefit of rosuvastatin was observed in patients with higher galectin-3 levels.
Conclusions:
- Low plasma galectin-3 levels (<19.0 ng/mL) may identify patients with ischaemic systolic HF who benefit from rosuvastatin.
- This post hoc analysis suggests a potential role for galectin-3 as a predictive biomarker for statin response in HF.
- Caution is advised due to the post hoc nature of the analysis and the overall neutral results of the CORONA study.
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.
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