Study should’ve randomized to either rosuva or atorva, etc, it was a secondary analysis though:
In the atorvastatin vs rosuvastatin we discussed different studies. Not just one.
The mg to mg comparison is irrelevant.
What matters is: take the lowest statin dose possible + ezetimibe. Actually given that statins can mess up with glycemic control I would argue to start with ezetimibe and if not enough add the lowest dose of ator (if diabetes or at risk of) or rosu (if not). Ezetimibe divided my ApoB by 2. I’m a hyperabsorber I guess.
Surprisingly it’s well proven in RCT but no one knows about it. See this thread: Omega 3 makes me depressed: why?
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Interestingly it was when i combined low dose atorvastatin(10mg) everyother day and 5mg Rosuvastatin on the alternate day that my LDL went to 1.2 . (from 5.5) Solo therapy of 40mg Atorvastatin only lowered LDL to 3.5 (from 5.5.) Solo therapy 20mg of Rosuvastatin was the same 3.3 .
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I tried the 6m pcsk9i Leqvio and was extremely unimpressed. As a solo therapy it only lowered LDL to 2.6 and my side effects-chronic cough , lethargy, brain fog(like early onset dementia!) were unpleasant. I would not sign up for a more permanent gene therapy-pcsk9i treatment.
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unless you are concerned about alzheimers… Atorvastatin in lipophilic and rosuvastatin is hydrophylic. The prevailing thought is that you don’t want to inhibit cholesterol synthesis in the brain so I’d choose rosuvastain over atorvastatin any day. Better yet Bempedoic acid if it gets your lipids where they need to be without the additional punch of a statin.
Probably the best case (maybe even only case) for daily 81 mg aprin is if you have high Lp(a).
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Yes I see the other study now. That’s interesting and I retract my statement about Atorvastatin being shitty. Thanks for the correction.
For me personally, Ezetimibe monotherapy was also reasonably effective. Actually more effective than statin monotherapy. So I think I’m with you in the hyper-absorber category, though mine is HeFH (heterozygous familiar hypercholesterolemia).
I’ll just use LDL-C in mg/dl as the illustrative examples. Here are my results:
No treatment: 180
Ezetimibe only (10mg/day): 140 (22% reduction)
Rosuvastatin only (10mg/day): 180 (i.e. zero effect) (0% reduction)
Ezetimibe and Rosuvastatin (10mg/day of both): 73 (60% reduction)
So as you can see, there is a synergistic effect from taking both, which I can’t really explain.
Then adding Repatha at 140mg 1x per month: 25 to 45 mg/dl depending on when I measure (86 to 75 % reduction)
My HBA1C never moved.
Thanks for the links. I’d never heard of that. As you pointed out in your first post, most things I read have people saying it made them less depressed. I can’t say I’ve ever felt anything from zero fish oil to 4g per day. But it’s always mixed DHA and EPA. I’ve never tried using only one of them.
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Yes that’s why the best is probably ezetimibe + BA. And one day obicetrapib?
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My experience too. Ator most effective between 10mg and 40mg. U shaped curve for me as 80mg added no value. But adding Ez was synergistic, bringing TC, LDL and ApoB in line
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I’m curious how much evidence there is regarding this? From what I’ve heard (not an expert on the brain at all), Alzheimers is also related to vascular dysfunction, and statins are generally protective of vasculature. From a quick search, I find papers showing reductions in Alzheimers use. Whether that’s from peripheral circulating cholesterol reductions, or brain-specific production I am not sure.
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High cholesterol is a modifiable risk factor for dementia. However, evidence is weak in favor of statins for dementia prevention. Still, lipophilic might be worse indeed: Statins and cognitive decline in patients with Alzheimer’s and mixed dementia: a longitudinal registry-based cohort study 2023
Lipophilic statin users compared to hydrophilic statin users
We did not find significant differences in MMSE decline in lipophilic statin users (simvastatin, atorvastatin, fluvastatin users) (Table 4) or when considering imputed values of missing MMSE, compared to hydrophilic statins users (rosuvastatin, pravastatin users). However, it was faster in incident users of lipophilic statins (1.32 less MMSE points per year, 95% CI: -2.46; -0.18), and 3.84 less points after 3 years, 95% CI: -7.28; -0.41), compared to hydrophilic statins (Supplementary table 6). These analyses were not statistically significant in sub-analysis of age groups and sex (Supplementary table 3).
So for dementia prevention:
- Lower cholesterol with non-statin therapies first (I’d start with ezetimibe based on Ezetimibe Reduces Alzheimer's Disease Risk (study) )
- If you need to add a statin, add the lowest possible effective dose of rosuvastatin (even 2.5 mg might be enough). If you don’t tolerate it or if you’re diabetes, you might prefer low-dose atorvastatin.
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The difference in passing the BBB between different statins not much apparently.
For passing the BBB and reducing brain cholesterol levels, thus correlated with serum desmosterol, pretty much one association paper linking serum desmosterol on MCI and AD (see this: Does low cholesterol cause cognitive impairment? Part II - Peter Attia).
Meanwhile all RCT’s as secondary endpoints are either neutral or positive and it’s investigated for dementia and healthspan in PREVENTABLE and STAREE.
I’d say on net statins probably reduce risk of total dementia, depends how much you weigh that desmosterol connection. I’d probably not be on statins now with E4 allele if it was easy and inexpensive to get apoB optimal without it or if I could test my desmosterol levels, but I’m unsure. I’d probably be on same stack as Peter Attia (bempedoic acid + ezetimibe + PCSK9i) until further evidence or new drugs.
Ezetimibe isn’t going to have enough of a lipid lowering effect on its own for most people, it lowers by 10-20%, so is going to need multiple meds.
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Yes, that’s why I wrote “I’d start with ezetimibe […] If you need to add a statin, add”. This means: “You START with ezetimibe then you test your apoB and if it’s still above your target you add another drug (bempedoic acid? low-dose statin? etc.).”
That being said, for hyperabsorbers, ezetimibe will most likely do the job. E4 carriers tend to be hyperabsorbers (source, I didn’t fact-check). So ezetimibe works for those who are the most at risk of AD.
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I didn’t miss that; just were setting expectations for people initiating ezetimibe monotherapy.
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I believe the “evidence” for reducing cholesterol synthesis in the brain = bad for Alzheimers comes from theories based on APOE alleles. APOE4 results in poor distribution of Cholesterol to neurons so it makes sense that you wouldn’t want to reduce Cholesterol concentrations in the brain. I’m not sure that’s “evidence”, circumstantial at best. That why I described it as “the prevailing thought”.
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Lp(a) reducing drug lepodisiran successful in phase 2 trials, phase 3 is ongoing.
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Long duration it seems
- Participants who received 400 mg of lepodisiran at both baseline and day 180 experienced a 94.8% reduction in average Lp(a) levels over the day 30 to 360 period, which remained 91.0% below baseline at day 360 (~1 year) and 74.2% below baseline at day 540 (~1.5 years)
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Any ETA on NDA filing with FDA?
Any ETA on NDA filing with FDA?
This one needs the phase three trials to first be fully enrolled and then read out the data of that
But there are others explicitly for Lp(a) and obicetrapib (for LDL, but still a big impact on Lp(a)) that seem to come out earlier
(Search the forum, recently discussed)
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