Is anyone concerned about shipping Praluent and Repatha given the temperature storage requirements? Seems that if you ordered overseas, Europe could make more sense than some Indian cities that are sporting 80F+.
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Are there any European sources for these drugs? I’ve not seen any (that you can purchase from in the US or elsewhere).
Ordering these drugs that need to be refrigerated, from India, definitely are a risk. There are multiple levels of risk too… have they been stored in refrigerated environments? Will they travel well from India given the lack of cold shipment options?
Given the low cost, it seems like it would be worth a try from India and test before and after to see if they work as advertised.
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Wow @DeStrider, I just checked in with my Indian source for rapa and the bempedoic acid/ezetimibe is like $10/mo! Definitely going to stock up on some and run a side-by-side – 3 months on PSCK9/ezetimibe and 3 months on bempedoic/ezetimibe. And maybe 3 months on all three just for curiosities sake (I think that’s what Attia does to get his ApoB <40).
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@RapAdmin
While I’m a big fan of Indian imports generally, I’m not sure I would want to get PCSK9 inhibitors from there due to the refrigeration/heat issues you mention given that you can get Praluent for $175/mo from Amazon Pharmacy (if you dose 150mg every 4 weeks). If somebody needs more apoB lowering than that, seems like it would be more cost effective to add bempedoic acid to the stack (from India) rather than increasing the dose of PCSK9 to 150mg every 2 weeks.
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Does anyone have insights into the plusses and minuses regarding the PCSK9’s Repatha vs Praluent?
There was a big discussion a while ago on ALM and PCSK9i studies a while ago and FOURIER trial in Rapamycin and risk of cardiovascular disease. From what I remember alirocumab might have better safety data. But check the thread, it was discussed in mid December.
It’s worth remembering that the low-desmosterol/Alzheimer’s connection is still only associational data, and people are hypothesizing that low DES from statin use could therefore drive AD. Yet despite this reasonable-sounding mechanistic case, statins have been robustly demonstrated to lower risk of Alzheimer’s and all-cause dementia, with no significant difference between lipophilic statins (which are more likely to reach the brain) and hydrophilic statins:
https://www.nature.com/articles/s41598-018-24248-8
If it were me making my own health decision, I would still lean toward DES testing and use of a hydrophilic statin. But the case is too weak to launch a major research investigation or have these become standard of care.
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Why this brand?
Bempedoic acid is a fairly new drug and still under patent in the US (I don’t know what its status is in India, though I see lots of vendors claiming to sell it). I can imagine shady operators selling pills labeled as BEMP that are actually statins and relying on people only checking LDL-C, if that. Aside from doing repeat n-of-1 testing with known statin and putative Indian-sourced “BEMP,” does anyone have any thoughts on how one might have more confidence that one were buying real BEMP?
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Isn’t desmosterol important factor in nerve myelination and responsible in regenerative processes in MS? Anyway I would not want my desmosterol levels very low in order to preserve nerve function and cognition…
Precisely. It is health optimizing for health concious people. Peter doesn’t have to take statins, he can take PCSK9 inhibitors, bempedoic acid and ezetimibe. Not everyone has the luxury to health optimize on the margin. Which optimizing for desmosterol is, because of the low expected value. Low dose statins shouldn’t decrease desmosterol by a lot. In 10 years the non-statin drugs will be cheaper and more evidence will build for or against. Until those 10 years happen I will gladly take a statin.
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I don’t think that’s clear (see this and this), but even if it were, that’s exactly the kind of mechanism-based speculation that I’m tallking about. The actual outcomes data from human randomized controlled trials and prospective epidemiology find a reduction in AD risk for both kinds of statin.
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It’s most likely one of those cases where the upside is bigger than the downside so there is a net benefit.
Rosuvastatin has some potential advantages over atorvastatin: - Higher potency - Rosuvastatin produces greater LDL reduction milligram-for-milligram compared to atorvastatin. Lower doses of rosuvastatin can achieve lipid goals. - Higher hydrophilicity - The polar nature of rosuvastatin results in less systemic absorption and tissue penetration, potentially reducing risk of muscle toxicity. - Greater HDL increase - Meta-analyses show rosuvastatin produces slightly greater increases in HDL cholesterol compared to atorvastatin. - Improved outcomes - The JUPITER trial with rosuvastatin showed reduced cardiovascular events in a primary prevention population"
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Brillo BA is made by the largest pharmaceutical company in India. It’s their Pfizer comparable. Usually the bigger the company, the better the product.
I can tell you it’s not just a statin as I am statin intolerant and I would be suffering severe muscle fatigue if it were just a statin in disguise.
Finally, if a company did repackage other drugs, that’s illegal and the government would probably notice and shut it down.
I’ll see what happens with my cholesterol the next time I measure.
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Thx for sharing, interesting quick read.
LDL-cholesterol reduction is a primary goal for reducing the risk of atherosclerotic cardiovascular disease: lower is better for lifetime, earlier is better, and lowest is best.
LDL-cholesterol is a driving force for broad spectrum, progressive pathophysiology and multiple disease states adversely impacting longevity and quality of life.
Many facts suggest that a desirable, physiologic level of LDL cholesterol is far lower than previously assumed:2
- Serum LDL-C in utero and in newborns averages 20–40 mg/dL (0.52–1.03 mmol/L). During gestation and after birth, humans are forming new cells at prodigious rates yet require little contribution of cholesterol from LDL.
- All cells of the body make their own cholesterol (plus a small portion derived from HDL-C).
- Those born with complete absence of proprotein convertase subtilisin kexin type 9 (PSCK9; loss of function mutation) suffer no ill consequences from lifelong near zero circulating LDL-C and have no atherosclerosis.
- Brown and Goldstein showed that fibroblast receptors for LDL are maximized at a concentration of 25 mg/dL (0.67 mmol/L) due to feedback control. Excess cholesterol beyond that is taken up either by hepatocytes or scavenger receptors on intimal macrophages that have no feedback control and thus accumulate much larger amounts of cholesterol.
- Randomized controlled trials (RCTs) and Mendelian randomization analyses demonstrate that there is log-linear relationship between atherosclerotic cardiovascular disease (ASCVD) and LDL-C at the highest levels down to near zero. The hazard ratio of 1.0 (meaning no excess risk) is achieved at an LDL-C of approximately 38 mg/dL (0.98 mmol/L).
- Many RCTs show that lowering LDL-C at any stage is beneficial, but doing so as early as possible is far better.
- Elevations in mid-life LDL-C also correlate with increased risk for neurologic disease, especially vascular and Alzheimer’s dementia, as well as Parkinson’s disease.
Considering this, the most desirable LDL-C appears to be that of the newborn, 20–40 mg/dL (0.52–1.03 mmol/L). Such a low level is likely not needed if LDL-C is well below 70 mg/dL (1.81 mmol/L) from birth, remains at that level through life and all other risk factors (hypertension, hyperglycaemia, obesity, inflammation, lipoprotein(a), and many others) are absent or well controlled. That is not common, but treatment can achieve it when needed.2
Unfortunately, most people are not entirely free from other risk factors.
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Just a note that ezetimibe is off patent in the US and super cheap here - so might want to so that for the extra margin of safety on that one
Eg here - 13-23 dollars for 90 days:
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If my doctor would prescribe it, I would certainly buy it here!
Perhaps just take your too high past cholesterol numbers to Push Health or similar service
Or just show them your other cholesterol prescription and explain that you want to try Eze instead
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Do the studies showing a reduction in dementia risk with statins break down between APOE4 and non-APOE4 carriers? If it had a benefit to non-carriers (75% of the population) and a negative effect on carriers, it might still have a population net benefit even if it were harming APOE4 carriers.
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Update time…two months ago I went off rosuvastatin 20mg due to low desmosterol levels and started taking Praluent 150mg once every 4 weeks (as opposed to every 2 weeks, to save money). My ApoB went from 87 on rosuvastatin alone to 112 on Praluent. This test was three weeks after my last Praluent dose. I’m pretty disappointed, as I expected Praluent to perform as well or better than the statin, even at the lesser frequency.
My ApoB was 121 back when I wasn’t taking anything, so the Praluent only marginally decreased ApoB from baseline. In fairness, back when I was on nothing I ate largely a pescatarian diet and I’ve been eating a lot more meat since starting the statin and then Praluent, so possible that I’m getting a bigger decrease than the baseline would suggest. Still disappointing.
Next I’ll add my Indian bempedoic acid and zetia to the mix and see what happens. Fingers crossed.
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