Polygenic Risk Score Identifies Subgroup with Higher Benefit from Intensive Statin Therapy in WOSCOPS

The West of Scotland Coronary Prevention Study (WOSCOPS) randomized 10,456 men with hypercholesterolemia to pravastatin or placebo. This post-hoc analysis derived a polygenic risk score (PRS) from 182 coronary heart disease-associated variants and tested whether genetic risk modified the benefit from statin therapy.

Among WOSCOPS participants in the highest PRS tertile, statin therapy produced a 45% relative risk reduction in coronary events — substantially greater than the 20% reduction seen in the lowest tertile. The PRS predicted event rates in the placebo arm independently of LDL-C and other traditional risk factors, and identified who was most likely to benefit from the intervention.

This is a foundational precision medicine analysis. It establishes that polygenic risk is not merely a label — it identifies patients with a genuinely elevated residual risk who derive disproportionate benefit from cholesterol-lowering therapy. The implication is that PRS testing could eventually be used to identify high-risk individuals who should receive aggressive lipid management even when their traditional risk factor burden does not clearly indicate it.

The post-hoc design and single-sex (male-only) cohort limit generalizability, but the WOSCOPS PRS finding has been replicated in subsequent analyses.

We rate the evidence strong. A rigorous post-hoc RCT analysis establishing that polygenic risk score stratifies statin benefit — a major step toward genomics-guided prevention.