Safety and efficacy of low-density lipoprotein-lowering drugs in the elderly: a network meta-analysis of randomized controlled trials.
TL;DR
Moderate-intensity pitavastatin showed the highest safety profile, while its combination with ezetimibe was the most effective for LDL reduction, suggesting greater efficacy in primary prevention.
Abstract
Background
Balancing the efficacy of low-density lipoprotein (LDL) reduction with safety presents a significant challenge in the elderly care. While guidelines recommended high-intensity statins as the optimal strategy to lower LDL in high-risk individuals, there are prevailing concerns regarding its side effects and subsequent fatality rate. The effectiveness of different LDL-lowering therapies in this population is also unclear. This study aims to compare the safety and efficacy of various LDL-lowering strategies in elderly population.
Methods
A systematic search was conducted through six databases until March 2025. Randomized controlled trials (RCTs) that evaluate LDL-lowering agents were included. The primary outcome was adverse effects, while secondary outcomes included composite cardiovascular disease (CVD) events, CVD related mortality, all-cause mortality, and LDL level reduction. Risk of bias was assessed using the RoB-2 tool. A network meta-analyses were performed to compare the safety and efficacy with subgroup analysis based on underlying CVD under the cumulative ranking values.
Results
Sixteen RCTs (n = 43,625) with low to moderate risk of bias were included. Among interventions evaluated for adverse events, moderate-intensity pitavastatin had the highest probability of being the safest. Ezetimibe demonstrated the most favorable safety profile for reducing CVD mortality, while evolocumab was most effective in lowering all-cause mortality. For LDL reduction, the combination of moderate-intensity pitavastatin and ezetimibe was the most effective, followed by moderate-intensity rosuvastatin plus ezetimibe. Subgroup analyses revealed significant differences between CVD and non-CVD populations in CVD mortality (P = 0.0059), CVD events (P = 0.0096), and LDL reduction (P = 0.0100), with more pronounced effects in the non-CVD group, suggesting greater efficacy in primary prevention.
Conclusions
Moderate-intensity pitavastatin showed the highest safety profile, while its combination with ezetimibe was the most effective for LDL reduction.