Statins in Heart Failure: Not yet the End of the Story?

We read with interest the article by Dobre et al. on the benefits of statin therapy to reduce all-cause death in acute heart failure (AHF),1 in contrast to findings reported by two large clinical trials in chronic heart failure (CHF), CORONA2 and GISSI-HF.3 In agreement with Dobre et al., we recently reported a lower mortality risk associated with statin treatment in a real-life cohort of CHF outpatients.4 Kaplan–Meier survival curves diverged early during follow-up in both cohorts (Figure 1). When comparing univariate analysis, statin use was associated with better prognosis in both studies for all-cause mortality and cardiovascular mortality (P < 0.001 for all comparisons). After multivariable adjustment, the risk of all-cause death also remained statistically significantly lower [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.69–0.92; P = 0.001 and HR 0.66, 95% CI 0.53–0.83; P < 0.001, for Dobre et al. and Gastelurrutia et al., respectively]. Dobre et al. suggest that from the perspective of the CORONA and GISSI-HF trials, their positive results may be explained by their population being ischaemic/post-acute myocardial infarction heart failure patients.1 However, our results showed a benefit in both ischaemic and non-ischaemic patients.4 Thus, an alternative explanation may be the fact that not all statins have the same properties. A recent meta-analysis, including the GISSI-HF and CORONA trials, observed that randomization to lipophilic statins showed a significant benefit not observed in randomization to rosuvastatin,5 a hydrophilic statin with poor penetration into extrahepatic tissue and very low uptake by cardiac muscle, opposite to simvastatin or atorvastatin. This new study does not state which statins were used, but it is conceivable that only a low proportion of subjects were on rosuvastatin, due to the fact that in real life, most patients take lipophilic statins. Despite the longstanding controversy on this issue, these data provide arguments to re-open the door for new prospective studies to assess statin benefit both in CHF and in AHF. Conflict of interest: none declared.