Paul Saladino· MD
but all of these uh drugs they're trying to raise HDL uh artificially invariably flopped in the clinical trust in fact several of them increased dramatically the risk of of uh hemorrhaging Strokes which is really nasty
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We can't find evidence that holds up here. Proponents are reasoning from mechanism or analogy rather than direct human data, and the most credible skeptics raise objections we can't dismiss.
but all of these uh drugs they're trying to raise HDL uh artificially invariably flopped in the clinical trust in fact several of them increased dramatically the risk of of uh hemorrhaging Strokes which is really nasty
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Bookmarking — the dossier-vs-overview split is the right call. Most of the time I want overview; sometimes I want receipts.
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although I would argue that that's not a good thing I think we have a pretty good sense of why raising HDL cholesterol in organically meaning pharmacologically is not going to be good
I encourage no one to ever make a judgment on any humans cardiovascular risk based on their high-density lipoprotein cholesterol level or think you know what you're doing to a human being if you somehow change that HDL cholesterol metric in that patient has nothing to do with anything
I think that those trials combined with the EMR have put an end to this this approach to lipid modulation
it raises HDL cholesterol turns out nice and doesn't work if you want to take legitimate trials to show it works
no no no i'm sorry there have been multiple clinical trials that have attempted to raise hdl cholesterol that's true yes and it's more than two drugs there are other drugs that yeah there's more than two mechanisms of action correct at least two that i can think of there might be there's probably three mechanisms of action that have been that would all raise hdl cholesterol but the point that you made that is should not be lost on anyone is at best those trials have been neutral as have the mendelian randomization trials looking at genetic surrogates of hdl and cardiovascular outcomes yes and at worst those trials have been harmful
efforts to raise hdl cholesterol pharmacologically have by and large mostly not exclusively but mostly failed in uh improving outcomes
efforts to raise HDL cholesterol pharmacologically have by and large mostly not exclusively but mostly failed in improving outcomes
it really is one of the key planks that has led to I think what is now Rock Solid which is HDL cholesterol itself the HDL cholesterol itself is not directly and causally protective against atherosclerotic cardiovascular disease