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Galectin-3 Predicts Response to Statin Therapy in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA)
Study Questions:
Can plasma galectin-3 (a mediator of fibrogenesis) predict patients with chronic heart failure (HF) for whom statins are effective?
Methods:
The study cohort was comprised of 1,492 patients with ischemic systolic HF, enrolled in the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) trial, who were randomly assigned to 10 mg/day of rosuvastatin or placebo. The study investigators measured plasma galectin-3. Cardiovascular death, myocardial infarction, or stroke were the primary outcomes.
Results:
A total of 411 patients had a primary event during a median follow-up of 32.8 months. An interaction between baseline galectin-3 and rosuvastatin on the primary endpoint was detected (p = 0.036). In patients with plasma concentrations of galectin-3 below the median (≤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).
Conclusions:
The study investigators concluded that rosuvastatin therapy may be beneficial in patients with systolic HF of ischemic etiology who have galectin-3 values <19.0 ng/ml. However, they cautioned that the data from this post-hoc analysis may be limited because the overall results of the CORONA study did not show a significant effect on the primary endpoint.
Perspective:
This is an important study because it suggests that galectin-3 may be an important biomarker in that it can predict the success of statin therapy in this cohort. As suggested by the study investigators, these findings should serve as a basis for a prospective study to validate these findings. A prospective study would require an approach that incorporates several biomarkers—a ‘multimarker’ approach that should better predict which patients are most likely to benefit from a therapeutic intervention such as statin therapy (Heart Fail Clin 2009;5:ix-xii).
Keywords: Natriuretic Peptides, Myocardial Infarction, Stroke, Biomarkers, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Heart Failure, Galectin 3, Hospitalization
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