LDL-C & heart disease – definitive proof?

Executive summary

* PCSK9s are relatively recent additions to the array of cholesterol lowering drugs. They are delivered by injection – fortnightly or monthly. One PCSK9 is called evolocumab.

* A 2023 paper reported on an update to the FOURIER trial (which was called FOURIER-OLE). FOURIER looked at cardiovascular outcomes in evolocumab vs placebo. FOURIER-OLE gave evolocumab to approximately 6,500 people from the FOURIER trial and then reviewed whether those in the lowest LDL-cholesterol group fared better than those whose LDL-C didn't fall as much.

* FOURIER-OLE concluded that endpoints were better in the lower LDL-C group and adverse events were no worse. That's the drug benefit proven, yes?

* Not necessarily. I reviewed several points as to why this may not be the case:

1) The characteristics of the patients who achieved the lowest LDL-C were very different to those who didn't.

2) Some of the cardiac endpoints were subjective and these skewed the results in favour of those with lower LDL-C.