Effects of Statins to Reduce All-Cause Mortality in Heart Failure Patients: Findings from the EPICAL2 Cohort Study

Abstract

Introduction The addition of statins to standard care in heart failure (HF) patients remains controversial in clinical practice. Large-scale clinical trials failed to show mortality benefits, but uncertainty persists in real-world settings. Objective We evaluated whether the prescription of statins at hospital discharge is associated with a reduction in all-cause mortality at up to 1 year of follow-up in HF patients. Methods We analyzed data from Epidémiologie et Pronostic de l'Insuffisance Cardiaque Aiguë en Lorraine (EPICAL2) cohort study of 2254 hospitalized acute HF patients who were admitted to 21 hospitals located in northeast France for acute HF between October 2011 and October 2012 and who received statins at discharge compared with patients who did not. We used propensity score matching and instrumental variable analyses to estimate the treatment effects of statins, and a multivariable Cox proportional-hazards model to examine survival with statin use, adjusting for patient demographics, HF characteristics, medical history, comorbidities, drug treatment and other known potential confounders. We plotted Kaplan-Meier survivor curves, and used log-rank test to determine the equality of survivor functions. Results We included 2032 patients in this investigation: 919 (45%) in the statin-treated group and 1113 (55%) in the control group. The estimated average statin-treatment effects for all-cause mortality in HF failed to demonstrate a significant effect on mortality [Z = − 1.73, 95% confidence interval (CI) − 0.11 to 0.007, p value = 0.083, and Z = − 0.95, 95% CI − 1.34 to 0.46, p value = 0.34] for propensity score matching and instrumental variable analyses, respectively. Moreover, the Cox proportional-hazards model showed that statin prescription was not significantly associated with the rate of death (hazard ratio = 0.85, 95% CI 0.66-1.11, p value = 0.26), adjusted for all confounders. Conclusion In patients with HF (and reduced or preserved ejection fraction), the prescription of statins did not appear to be associated with better survival after 1 year of follow-up in the EPICAL2 cohort. We cannot exclude that a subpopulation of HF patients may have some benefits compared with the whole HF population or that there might be a lack of power to show such effect. Clinical Trial Registration NCT02880358.

Effect of Statins on All-Cause Mortality in Adults: A Systematic Review and Meta-Analysis of Propensity Score-Matched Studies

“…A total of 665 citations were identified, and 210 potentially eligible articles were retrieved in full text. Overall, 54 studies were included in the review ( Figure 1 ) [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ]. Risk of bias assessment using NOS showed that the studies have low risk of bias.…”

Impact of lipophilic vs hydrophilic statins on the clinical outcome and biomarkers of remodelling in heart failure patients: A prospective comparative randomized study

“…In the present study, there was no significant difference between statin groups in Packer's composite outcome, change in functional class (NYHA), the incidence of hospitalization and cardiovascular events. In cohorts of statin treated HF patients, statin use was not associated with improvement in clinical outcomes nor survival after 1‐year follow‐up in HF with reduced ejection fraction 49,50 . However, in a prior indirect comparative metanalysis, lipophilic statins were reported to reduce cardiovascular and noncardiovascular mortality and hospitalization for worsening HF compared to hydrophilic statins with no difference in cardiovascular hospitalization 15 .…”

“…In cohorts of statin treated HF patients, statin use was not associated with improvement in clinical outcomes nor survival after 1-year follow-up in HF with reduced ejection fraction. 49,50 However, in a prior indirect comparative metanalysis, lipophilic statins were reported to reduce cardiovascular and noncardiovascular mortality and hospitalization for worsening HF compared to hydrophilic statins with no difference in cardiovascular hospitalization. 15 Additionally, in a recent comparative study, atorvastatin showed better long-term outcomes, including rehospitalization rates and mortality, compared to rosuvastatin treated HF patients.…”