YouTube· The Lancet · YouTube·· 14 hours agoScore38
25 Years of Lipid Medicine: One Stubborn Number, a Lancet Retrospective
In brief
The Lancet reviews 25 years of lipid-lowering evidence. In 2001 the US NCEP set the LDL target for high-risk patients at <2.6 mmol/L; high-intensity statins, ezetimibe, and PCSK9 antibodies (an approximately 60% reduction) then progressively confirmed that the key was never statins themselves but LDL, and the target has tightened to 1.4 mmol/L.
Key points
A 'time capsule' style retrospective from The Lancet: 25 years of evolving evidence on lowering LDL/cholesterol and 'one stubborn number'.
- Timeline: In 2001 the US NCEP set the LDL target for high-risk groups at <2.6 mmol/L; subsequently high-intensity statins consistently outperformed moderate-intensity statins, with lower LDL meaning fewer cardiovascular events. A 1.8 target was added in 2004, but progress then stalled (fibrates, niacin, and HDL-raising drugs showed no additional benefit).
- The 2013 guidelines briefly abandoned targets; after years of debate, the non-statin drug ezetimibe confirmed the principle by reducing events in proportion to the 'additional LDL lowering'—the key was never statins themselves, but LDL.
- Present day: PCSK9 antibodies lower LDL by about 60%; RNA drugs (such as siRNA, once every six months) turn off protein synthesis at the source; gene editing may work with a single dose (an early PCSK9 editing program was temporarily halted due to serious adverse events).
- Current status: the target has been tightened to 1.4 mmol/L, but only about 1/3 of high-risk patients reach it—'the science of lowering cholesterol is largely settled; delivering it to those who need it is not'.
Source: YouTube