Fantastic writeup on atorvastatin, Jonas! The big advantage atorvastatin has over some of the other LLT (Lipid Lowering Therapies), is a lengthy track record. That said, all it means, is that if other LLTs (including newer statins) are superior for health/lifespan they may not appear so because they don’t have the atorvastatin length record. If that is so, springing for other LLTs than atorvastatin involves something very risky, i.e. mechanistic speculation (which I am loath to do, knowing how risky such reasoning can be!). However, if you are willing to take the risk…
This is where I come in with an n=1 experiment, which I’m about to commence, the outcome of which is highly uncertain. I have been on 10/mg atorvastatin for some 5 years, after a lifelong high TC, LDL, ApoB and very high Lp(a) - currently 66 years old. Additional factor: at age 65 I had a CAC scan that returned a score of 0.
Initially the atorvastin has been highly effective, bringing my LDL to the low 70’s, and TC in the 150-160 range. However, every year, my numbers got worse and worse, and now my LDL is in the 130’s range. I don’t fully understand why, as I have not changed my (excellent) diet or exercise regimen - we do know that with age, LDL tends to go up, so maybe that’s a factor? Incidentally, I tried finding out if perhaps statins can lose effectiveness over time, but it’s been surprisingly difficult to google that info.
My PCP is very resistant to doing anything to ameliorate the situation by adding other LLTs, so I’m left to my own devices. My initial plan - which I have posted about here on other threads - involved keeping the 10mg/day atorvastatin, but adding 180mg/day Bempedoic Acid and 10mg/day Ezetimibe.
Yet, just recently I have decided to change my plan. Now my plan is to switch from atorvastatin to 4mg/day pitavastatin based on a lot of reading and some dodgy, questionable, risky mechanistic speculation.
Here is my reasoning. I want to keep taking a statin, not only because of the lipid lowering effects, but for pleiotropic benefits (cancer, ACM, etc.). If I am to keep taking a statin, then which one should I take? Atorvastating 10mg/day has been increasingly failing. I could raise the dose, but the additional LDL lowering seems much smaller. I am not convinced by rosuvatatin, so what other potent statin should I switch to - it looks to me like pitavastatin is the best candidate. I italicized the most important points from my POV.
1)Pitavastatin is more potent than either atorvastatin or rosuvastatin.
2)It has both mildly lipophilic and hydrophilic properties, while atorvastatin is all in on lipophilic and rosu on hydro.
3)Pitavastatin lowers hsCRP significantly, whereas ator barely so - this means that possibly pita pleio bennies driven by lowering systemic inflammation might be superior
4)Pita compared to ator lowers CV events to 2.9% vs 8.4% (study I can post) - so vastly superior to atorvastatin!
5)Pita has no known deletrious effect on liver compared to ator (the latter has some - very low - liver toxicity, but possibly that’s due to much larger group of patients, and hence reporting vs pita)
6)Pita has no real BG or Ac1 effect compared to ator - I care, because I’m pre-diabetic
7)Pita is remarkably inert wrt. other drugs interaction!
8)Pita users have lower ACM
Wrt. the point (7), I find this paper very persuasive - it’s a long paper, so I’ll just give the relevant quote:
Quote:
** Pitavastatin is a lipophilic statin which has a very high bioavailability of 50% (43–51%) and is practically not metabolised in the body by the cytochrome P450 3A4 system (to a minimal extent – close to 3% – metabolised by CYP2C9 and CYP2C8), which significantly reduces the risk of interaction with other drugs (Table II) [47, 50, 51]. Pitavastatin does not exist as a prodrug, is 99% protein-bound in blood and its metabolites are inactive [51]. In an analysis by Gosho et al . involving three RCTs and real-world data, it was found that concomitant administration of pitavastatin with other medicines was not associated with a clinically significant increase in the incidence of adverse drug reactions, even when administered with agents that interact with CYP2C9, which is responsible for minimal metabolism of pitavastatin. In addition, a significant interaction of pitavastatin with biguanides was found, but this was associated with a reduced risk of muscle-related side effects [52]. The high bioavailability of pitavastatin means that it is administered at much lower doses (1, 2 or 4 mg) compared with rosuvastatin (5, 10, 20, 40 mg) or atorvastatin (10, 20, 40 80 mg), which can be used as an argument to convince patients who are concerned about high doses of these medicines (and reduce the risk of nocebo/drucebo effect [53]). The relatively long half-life of pitavastatin means that it is irrelevant at what time the medicine is taken, whether in the morning or in the evening [50].**
This is a key quote, but there is a lot more interesting material wrt. pita vs muscle pain and so on, so this paper is quite interesting starting from the section I quote onward too.
In any case, the stack that I’m contemplating ordering from the Indian pharmacy is rapamycin, empagliflozin, pitavastatin and telmisartan. I’m dropping bempedoic acid and ezetimibe for now. My LDL goal is below 70 - if I can achieve that solely through 4mg pita, then great. If not, I’ll then look to add eze and/or BA. Now, obviously, there are some unknowns - I tolerate ator very well, who knows if I’ll tolerate pita equally well… it’s always a gamble.
However, the fact that pita is relatively inert vs other drugs is a key consideration for me, because engaging in any polypharmacy you always look for the risks. From that point of view, if I am to have a statin, pita seems ideal for that scenario. Additionally, the fact that pita doesn’t significantly affect BG and Ac1, is a key consideration (especially for a pre-diabetic) because rapa might raise both lipids and blood glucose. So, if I want a statin that will be powerful enough to significantly lower lipids and not raise BG, because of rapa, seems pita is the ideal candidate, throw in fewer drug interactions and side effects and it seems like a no-brainer.
I intend to do the following: get a complete blood workup with a lipid panel (including all ApoB subfractions etc.), glucose, a1c, liver and kidney panels and so on. Then drop ator in favor of pita. Give it a few weeks, re-do the blood test to see the effect of pita. If LDL is not below 70, reassess whether I should get on +/- eze & BA. If all looks good on the lipid front, throw in rapa starting with 3mg/1-week for 4 weeks, 4mg/1-week for 4 weeks, 5mg/1-week for 4 weeks, and 6mg/1-week for 12 weeks and then do another complete blood workup. If all looks good (especially BG and lipids), throw in empagliflozin, re-test in 90 days to see what a1c is up to. Finally throw in telmisartan. Re-test, and go from there.
One key thing, before anything, starting in October get a CGM (one of the OTC ones, probably Abbott, depending on reviews), which I intend to stick with for 18 months or so for the full stack to be implemented, so I can monitor BG at all times.
Anyhow that’s the battle plan. But as we know, once the war starts all battle plans are thrown up into the air, lol! We’ll see.
