The role of lipid lowering medications in the primary prevention of cardiovascular disease and mortality: a meta-analysis of randomized controlled trials.

IMPORTANCE: The mortality benefit of lipid-lowering therapies (LLTs) in true primary prevention of cardiovascular disease (CVD) remains uncertain, in part because prior studies frequently included individuals with existing cardiovascular, vascular, or cerebrovascular disease. OBJECTIVE: To evaluate the effect of LLTs on all-cause mortality and major adverse cardiovascular events exclusively in patients without prior CVD. DATA SOURCES: MEDLINE, EMBASE, and COCHRANE were searched through October 2024 for randomized controlled trials (RCTs) comparing LLTs with control therapy. STUDY SELECTION: RCTs assessing LLTs for primary prevention and reporting mortality or cardiovascular outcomes were included; trials with any participants with prior CVD, vascular disease, or cerebrovascular events were excluded. RESULTS: Ten RCTs including 85,829 participants, met criteria. LLTs did not reduce all-cause mortality compared with control (3.9% vs. 3.9%; RR 0.98, 95% CI 0.89–1.07) or cardiac mortality (1.4% vs. 1.5%; RR 0.92, 95% CI 0.82–1.04). However, LLTs—primarily statins—reduced MACE (RR 0.76, 95% CI 0.68–0.84), myocardial infarction (RR 0.64, 95% CI 0.57–0.72), revascularization (RR 0.70, 95% CI 0.57–0.86), stroke/TIA (RR 0.75, 95% CI 0.57–0.98), and cardiovascular hospitalizations (RR 0.75, 95% CI 0.65–0.87). CONCLUSION: Among individuals without prior cardiovascular, vascular, or cerebrovascular disease, LLTs did not reduce all-cause or cardiovascular mortality but were associated with significant reductions in nonfatal cardiovascular events. Additional research is needed to define the benefits of LLTs in true primary prevention.