Lipid-lowering therapy for primary prevention of cardiovascular disease in adults aged 75 years and older: a narrative review

Background: Adults aged 75 years and older carry the highest absolute risk of cardiovascular disease (CVD) yet remain substantially underrepresented in randomized trials evaluating statin therapy for primary prevention. This evidence gap creates uncertainty regarding the appropriateness of initiating lipid-lowering therapy in this population. Methods: We conducted a narrative review of randomized controlled trials, meta-analyses, and large observational studies evaluating statin therapy for primary CVD prevention in adults aged 75 years and older. We searched PubMed and reference lists of relevant articles through December 2024. Results: Direct randomized evidence for primary prevention in adults over 75 years is limited. The PROSPER trial included a mixed population of primary and secondary prevention patients aged 70-82 years. Post-hoc analyses of ALLHAT-LLT showed no benefit and a trend toward harm in patients aged 75 years and older. Meta-analyses of observational data suggest mortality reductions of 12-14% associated with statin use, though subject to confounding. The time to benefit for cardiovascular event reduction is approximately 2.5 years, which must be weighed against individual life expectancy. Conclusions: Current evidence does not support routine statin initiation for primary prevention in all adults over 75 years. Treatment decisions should be individualized based on cardiovascular risk, life expectancy, frailty status, patient preferences, and competing health priorities. Results from the STAREE and PREVENTABLE trials, expected in 2025-2027, will provide definitive guidance.