Numerous lines of evidence, including randomized controlled trials, single gene studies, and Mendelian randomization studies, are not consistent with your inter

Numerous lines of evidence, including randomized controlled trials, single gene studies, and Mendelian randomization studies, are not consistent with your interpretation. Multiple agents that reduce cholesterol, including ezetemibe and statins, reduce cardiovascular disease outcomes and death. Multiple cholesterol-related genes, including HMGCR, LDLR, APOB, PCSK9, and ANGPTL3, contain variants which influence both LDL cholesterol and the risk for coronary artery disease, myocardial infarction, and death. And Mendelian randomization studies that rely upon a dose-response relationship between genes that influence cholesterol and the cardiovascular outcomes that they cause have also demonstrated a link between genetically driven cholesterol levels and hard endpoints. So, one set of drugs (CETP inhibitors) that don't seem to follow the story are more likely to be the exception, rather than the rule. Interesting biology awaits us in the explanation of why the CETP inhibitors don't do what we imagined they would with hard outcomes.