As Baseline LDL Falls,
Mortality Benefit Shrinks
Each bubble is a major lipid-lowering RCT. The x-axis is the baseline LDL of enrolled patients. The y-axis is the absolute reduction in mortality — how many deaths were actually prevented per 1,000 patients treated. Bubble size reflects trial enrollment.
Early era 1994–2002
Mid era 2003–2010
Modern era 2011–2022
VESALIUS 2026
Mortality formally significant
Non-significant or exploratory
CV / vascular mortality — absolute risk reduction
CHD, CV, or all-cause mortality depending on trial · zero line = no benefit · solid bubble = formally significant
All-cause mortality — absolute risk reduction
All-cause mortality where available · same axes for direct comparison · solid bubble = formally significant
ARR = (control arm mortality rate − treatment arm mortality rate) × 1,000, from published event counts and follow-up. Mortality endpoint varies by trial — CHD death (4S, WOSCOPS), vascular/CV death (CARE, LIPID, HPS, FOURIER), or all-cause (ODYSSEY Outcomes, VESALIUS). Bubble size ∝ enrollment. Dashed regression line is OLS. Vertical dashed line = VESALIUS median baseline LDL (122 mg/dL ★). VESALIUS mortality is exploratory — hierarchy broke at CHD death alone (p=0.39). VESALIUS exploratory FOURIER: CV mort ARR ~0.8/1,000
Sources: CTT Collaboration Lancet 2005/2010/2015 · FOURIER NEJM 2017 · ODYSSEY Outcomes NEJM 2018 · VESALIUS NEJM 2026