Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: a reanalysis based on regulatory data - bmjopen.bmj.com/content/12/12/…

"In the meantime, clinicians should be sceptical about prescribing evolocumab . . ." The FOURIER trial showed no reduction in total or cardiovascular mortality. Our readjudication of mortality outcomes showed that deaths of cardiac origin were numerically higher in the evolocumab group (113) than with placebo (88) . . ."

"We observed an inverse association between LDL-C and 10-year all-cause mortality risk among 3,239 older adults without using lipid-lowering agents."

"Participants with the lowest LDL-C concentration showed the worst survival . . ."

frontiersin.org/articles/10.33… "We excluded participants who died within the first 2 years of follow-up and those with functional impairment to prevent reverse causality."

"By extensively reviewing the existing evidence, we could reasonably conclude that most lipoproteins enter the wall of large arteries not from the lumen by transcytosis but through the vv [vasa vasorum] . . ."

hindawi.com/journals/omcl/… "Although the most accepted theory regarding atherogenesis is endothelial dysfunction and lipid retention, there is sufficient evidence to support further research into the role of stress injury on human VV in the initiation of atherosclerosis."

onlinelibrary.wiley.com/doi/pdfdirect/…

"Expectations that unsaturated fats are “good” and saturated fats are “bad” are oversimplified and inadequate." (Bill Lands, 2022)

https://twitter.com/lipidchronicles/status/1465357387586547716

"While low intakes of n-3 and n-6 nutrients meet human needs, the discovery of harmful n-6 eicosanoid actions in inflammatory and thrombotic processes raises concern for whether there is a therapeutic window of healthy intake above which adverse conditions may occur."

". . . analysis of RCTs needs to provide absolute risk reduction, number of patients needed to treat, fragility index (FI) along with estimation of lost to follow-up (LFU) patients, and outcome postponement (gain in survival time)."

pubmed.ncbi.nlm.nih.gov/34983917/ "The findings of RCTs are routinely expressed as relative risk reduction (RRR = absolute difference (ARD) in effectiveness divided by the absolute risk (AR) in the comparator group) or hazard ratio (HR)."

EAS Consensus Panel includes the PRECISE-IVUS trial in their ecological graph on the left.

On the right is what the PRECISE-IVUS trial actually showed on an individual level - essentially no relation between LDL and plaque volume. EAS Consensus Panel: includes the ASTEROID trial.

What the ASTEROID trial actually found: LDL reduction not related to atheroma regression.

Decided to make a thread on the failures of apoB or LDL-P. All related info on this topic will go here. The AURORA trial: no relation between LDL or ApoB and major cardiovascular events - karger.com/Article/Abstra…