Real-World Long-Term Safety of Statin-Fibrate Combination Therapy in Older Patients (≥75 Years): A European Cohort...

Background: Given the increasing prevalence of dyslipidemia and multimorbidity in the older patient population, the lack of safety data on combined statin-fenofibrate therapy in this age group represents a critical gap. The post hoc subgroup analysis of the POSE study addresses this issue. Materials and Methods: The POSE study was a 3-year, real-world, observational, comparative, non-interventional study conducted in Europe. Patients with mixed dyslipidemia treated either by a fixed-dose combination of pravastatin 40 mg/fenofibrate 160 mg or a moderate-intensity statin monotherapy were enrolled. Safety outcomes included the occurrence of renal or urinary disorders, musculoskeletal or connective tissue disorders, hepatobiliary disorders, cholelithiasis, thromboembolic events, pancreatitis, worsening diabetes mellitus, elevated blood homocysteine levels, interstitial pneumopathy, phototoxicity, and fatal or non-fatal cardiovascular events. Laboratory parameters related to lipid control and renal, muscular, and hepatic functions were additionally evaluated. The post hoc analysis focused on a subgroup of patients aged 75 years and older. Results: A total of 458 patients were included in the analysis. The majority had hypertension (79.3%) and diabetes mellitus (55.0%). Over the 3-year study period, the incidence rate of composite safety events was numerically higher with the combination, though this did not reach statistical significance (RR = 2.18 [95% CI = 0.99-4.81]). Renal and urinary disorders were more frequent with the combination (5.5% vs. 0.8%), whereas musculoskeletal disorders, aggravated diabetes mellitus, and cardiovascular events showed no significant difference between groups, as the 95% confidence interval included 1. Globally, there were no significant differences regarding evolution of the hepatic, muscle, and renal biological parameters. From baseline to Year 3, TG levels decreased by 44.3% with pravastatin/fenofibrate and by 10.7% with statin monotherapy, while HDL-C levels increased by 26.5% and 0.4%, respectively. Conclusions: This real-life observational post hoc subgroup analysis suggests that in patients aged 75 years and older with mixed dyslipidemia at high or very high CV risk, pravastatin 40 mg/fenofibrate 160 mg demonstrates an acceptable long-term safety profile. The combination offers additional TG lowering and HDL-C improvement beyond moderate-intensity statin monotherapy, without a significant increase in overall safety events over three years.