Efficacy and Safety of More Intensive Lowering of LDL Cholesterol: A Meta-Analysis of 26 Randomised Trials

This is the Cholesterol Treatment Trialists’ landmark analysis — among the most cited and most decisive documents in all of cardiovascular medicine. (It is the same core dataset analyzed in the Baigent 2010 entry; both report the CTT’s 26-trial individual-patient meta-analysis.)

Its findings established the laws that govern cholesterol treatment: every 1 mmol/L (about 39 mg/dL) reduction in LDL cuts major vascular events by 22 percent; there is no threshold below which benefit ceases, so lower remains better even at very low levels; the benefit is consistent across patient subgroups; and statins carry no increased cancer risk and only a tiny, vastly-outweighed increase in hemorrhagic stroke. It also nudged practice toward the more potent statins.

These conclusions form the evidentiary backbone of essentially every modern cholesterol guideline. They are why “lower LDL, by whatever effective means” became the organizing principle of prevention.

We rate the evidence at the very top of this library. An individual-patient meta-analysis spanning 170,000 participants in randomized trials is the strongest evidence clinical medicine produces.