Efficacy of Statins for Primary Prevention in People at Low Cardiovascular Risk: A Meta-Analysis

This systematic review and meta-analysis examined the efficacy and safety of statins for primary prevention specifically in people at low baseline cardiovascular risk — a population where the absolute risk reduction from treatment is small and the benefit-to-harm balance is less certain than in high-risk populations.

Statins reduced all major cardiovascular events and total mortality in primary prevention populations, including at low baseline risk (10-year cardiovascular risk <10%). However, the absolute risk reductions were small: NNT for mortality was approximately 400, and for major cardiovascular events approximately 200, over 5 years. Adverse events, particularly myopathy and modestly elevated diabetes risk, were concentrated in this lower-benefit population.

The clinical relevance of this meta-analysis is the explicit quantification of NNT at low absolute risk — a perspective that changes the benefit framing compared with high-risk populations where NNT is substantially lower. For a patient at 5% 10-year risk, treating 400 people for 5 years to prevent one death is a real benefit, but the shared decision-making conversation differs fundamentally from treating a patient at 30% 10-year risk.

This analysis reinforces the importance of absolute risk calculation (not just relative risk reduction) and informed patient decision-making in primary prevention. CAC scoring, which identifies the subset of “low-risk” patients who actually carry subclinical coronary burden, is particularly valuable in this context: CAC=0 allows deferral; elevated CAC reclassifies into a higher-benefit treatment group.

We rate the evidence strong. A well-powered meta-analysis establishing that statins benefit even low-risk primary prevention patients but with small absolute risk reductions — key evidence for calibrating NNT expectations in primary prevention decision-making.