First I’d make 100% sure that you’re actually getting muscle pain from Repatha and/or bempedoic acid because that doesn’t make sense to me. Personally I can’t tolerate any statin (including low dose pitavastatin), but I have zero muscle/joint/pain issues with combination Repatha/bempedoic acid/ezetimibe therapy.
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Statins always cause muscle fatigue in me. It’s not pain, it’s a feeling of weakness. The less of a dosage I take, the less the weakness manifests.
I switched to Pitavastatin about a month ago, and my muscles have never felt better. According to the literature, my ApoB and LDL values should be similar to those if I were taking Atorvastatin 10 mg daily. Before I was taking 5 mg Atorvastatin EOD. So I get a more effective reduction in cholesterol and less muscle weakness. It’s a win-win.
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From the research I’ve read, when you have multi-class lipid medication, musculoskeletal side-effects, there is a mitochondrial “defect”. It is not a rare occurence, for people to not tolerate any of the lipid lowering medication: -therefore I was wondering if on this forum there might be a few experimenters with this uncommon problem who have found a work-around and will save me years of trial and error.
Most people only react to one or two classes of lipid lowering medication. If you examine the drug insert of Repatha, musculoskeletal is the #2 side effect, BA-it is #2, statins #1, praulent #1, inclisiran #3, . There are different periods of onset for me -BA takes 2 months, statins 3 days (pitavastatin takes a few weeks) Repatha is like a freight train on day 3. I have gone on and off all of them to ensure the problem is real and repeatable.
So again- there must be a few people with this issue, who have come up with a partial solution or maybe someone has seen research with a possible answer. Thx in advance for any advice
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What about siRNA like inclisiran that’s taken twice a year? Keep in mind the effects are long lasting.
Thomas Dayspring has had muscle issues on Ezetimibe, so it could be possible, albeit rare.
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FWIW, it was commonly accepted for a long time that ezetimibe couldn’t cause myalgia. But when Tom Dayspring (the renowned lipidologist) - who is statin intolerant, despite being a big believer in the effectiveness of statins - took it, he experienced the classic myalgia response with confirming biomarkers. He was told “it’s impossible” - until years later, it was found that yes, ezetimibe can cause myalgia. What I find very thought provoking, is that all these LLTs, have different MOAs, some dramatically so, yet they all can cause myalgia. Hmm. What do all these LLTs have in common? That’s an interesting phenomenon worth exploring - I bet we can learn a lot about lipids in human physiology by exploring this.
Is it about lowering lipids period, for some people? Perhaps below a certain level? There do seem to be some dietary ways to lower LDL for example (like certain fibers), and even non-pharmaceutical means (blood filtering) - I wonder if lowering lipids through those means would still result in myalgia?
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jinx: re Tom Dayspring, lol!
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That’s weird that we said it at the same time lol. It’s also quite esoteric.
Many of the LLT IIRC increase risk of diabetes or insulin resistance in MR studies, based on LDL lowering, although low and probably mitigated, or even worth it for some people. There was after all a new trial showing massive reduction in events and ACM for diabetics using a PCSK9i.
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I can attest to ezetimibe to causing myalgia! I always assumed it was neutral but it is close to statins in effect and onset time.
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I forgot and skimmed over that you had tried inclisiran. Keep in mind typically side effects like these are not for an entire drug class, some will have one statin work for them over the other. So just testing different brand of drugs until you find one with the composition that doesn’t cause this side effect for you might be an option. That’s normally recommended for a statin drug intolerance. E.g you might try other statins, or the other PCSK9i. If you do this for awhile and it doesn’t work, maybe Obicetrapib will arrive and work for you then.
Yes, there’s certainly variability among people. On the other side of it, people like me appear not to experience side effects from multiple LLTs. I had none with atorvastatin (though I only took 10mg for the 6 years or so that I took it), pitavastatin 4mg (over a year at this point), BA on its own (180mg), EZ on its own (10mg), then combined Pita(4mg)+BA(180mg)+EZ(10mg) for close to a year. As a side note, I was reminded again to be super cautious in blaming a drug for coincidental symptoms when I wrongly (in my mind) briefly suspected BA of causing severe muscle-joint issues which transpired to be entirely due to cervical disc degeneration (and had ACDF surgery to resolve) - one day I should write a post on the lessons learned (again!) about being extra careful to attribute cause to coincidental symptoms.
FWIW, in reading various papers on side effects of statins, apparently just because you don’t experience issues such as myalgia from statins, doesn’t mean that the statins are not having a somewhat deleterious effect on muscle tissue - this effect seems universal, because it’s down to how statins affect calcium channels. It’s just that for some reason only a percentage of people experience actual pain and other more severe symptoms - it’s along a spectrum with fatal rhambdo as an extreme. I did find that interesting, though when I suspected BA (wrongly) of causing me muscle problems, I ordered a Creatine Phosphokinase (Total) test at UCLA, in order to see if there was any enzymatic signature of muscle injury. So at UCLA labs, the CK “normal” range is 63-473/UL, with numbers above that range representing more muscle damage. Mine came in at 68, lol! Super low - barely above the lower level of normal. Zero injury, at least according to that test. And reminder, I had that 68 result while being on triple LLT - pita 4mg, BA 180 mg, EZ 10 mg - each drug at max dose! If any of these were causing muscle injury that released CK, this would be the time to see it - instead, Total CK was super low!
But here’s a plot twist. Despite the extensive triple LLT, my LDL levels have not dropped dramatically. I documented this extensively on this site when I tried a variety of combinations of statins BA and EZ as well as mono therapy. Further interesting point - my LDL without any LLT was pretty high, though not insane (140-160 mg/dL) - with TC 220-240 mg/dL. Atorvastatin was effective in lowering it fairly dramatically the first year I used it (10mg/day), down to LDL of 73 mg/dL at its lowest - but as time went by, each year the results got worse and LDL kept climbing until at 146mg/dL I quit atorvastatin and switched to pitavastain 4mg - it dropped my LDL, though not dramaticall (120’s), adding BA 180mg and then EZ 10mg on top finally pushed it to my current numbers: LDL 94 mg/dL, HDL 78 mg/dL, TC 187 mg/dL, Trigs 80 mg/dL. So, not super low. Is it possible that my not experiencing any sides from these LLTs is somehow related to them not being especially effective in lowering my lipids? I suppose there must be studies exploring these relationships.
If it were me, I’d give ergothioneine supplementation a try, since the leading theory of statin myopathy is mitochondrial oxidative stress and ergothioneine is a potent mitochondrial antioxidant, occurs naturally in mushrooms, is orally bioavailable and our mitochondria are ready to absorb and utilize it via very specific uptake transporters. I have no idea if someone has already thought of this and tried it.
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Interesting. I need to go recheck my lipids since I switched from 2.5mg Rosuvastatin to 2mg
Pitavastatin. I have been able to lift weights much more pain-free since I switched. If I find my LDL to be higher all of a sudden, maybe it’s because of that.
Wasn’t the previous thought that lowered CoQ10 was the possible cause of myalgia? Even though it hasn’t been shown to improve that across most studies.
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You are probably right. All the LLT’s are incredibly effective for me. I can drop LDL and triglycerides like a rock. If I take partial doses I get partial improvements in LDL but merely a longer onset for the myalgia
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COQ10 theoretically reduces myalgia, but everyone that I know who suffers from myalgia, taking COQ10 did nothing. Switching to the correct LLTs that reduce or eliminate myalgia is important and it is different for each person.
IMHO, the correct combination for me is Pitavastatin, BA and Ezetemibe. LDL and ApoB in the 48-58 range. That’s good enough for me! I don’t feel like adding a PCSK9i to reduce it below that level.
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What about apoB?
Unfortunately, I didn’t always get ApoB measurements. But as an example, in 2023, LDL was 114 mg/dL, while ApoB was 110 - this was with only atorvastatin 10mg/day. Most recently, LDL at 94 and ApoB 76 (ApoA1 192) on max dose triple LLT.
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So -18% LDL and -34% ApoB and ApoB close to the 70 mg/dL target. That’s why one shouldn’t rely on LDL.
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Hey Beth, sorry I don’t know anything about PCCT. But I’m sure these new techniques are amazing. Even Cleerly is incredibly impressive IMO.
However, from what I’ve read and remember, you’re on aggressive lipid management with 2-3 different drugs, you’re using colchicine for anti-inflammation, your blood pressure is low, you look after your diet etc etc.
So my overall question for any of these scans is: would it change what I’m doing? Or, how is this information helping me? Maybe you get a fancy scan that tells you an exact % of occlusion of the RCA, and what % is soft or calcified. I think Claude is totally right that you can characterise your plaque - but then what would you do with that information?
Let’s say it comes back and say you have almost no soft plaque and no meaningful artery occlusion. Are you going to stop taking all the therapies? Or what if it says your RCA is 70% soft plaque? Are there any more interventions on the table? Maybe the only one is a stent, but it’s already been shown that implanting stents doesn’t reduce cardiac events. (And, you’re asymptomatic and nailed a stress test).
I hope this doesn’t sound too cynical or dismissive or anything. I could see that if you were obese burger addict with horrible lipids, hypertension etc and the doctors are trying to decide a course of action, whether to do artery bypass surgeries etc, these would be amazing tools. But for someone like you I can’t really see a reason. (But again, I am not a cardiologist!)
Yes, having an experiment of plasmapheresis versus lipid-lowering drugs would be super interesting.
That said, all the data still says that these side effects aren’t that common. So either it’s under-reported in studies versus reality, or it’s over-exaggerated in certain places versus reality. I don’t think members of this forum are lying when they say they’re statin intolerant, but the published real-world incidence is apparently way less than 10%.
For me personally, 10mg Rosuvastatin, 10mg Ezetimibe and I have zero noticeable size effects. I hit the gym regularly, don’t max out, but I’m sure I could still bench ~100kg if I needed to. Nothing special at all in terms of strength, endurance, recovery. My CK, ALT, AST etc are all totally normal.
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This is exactly what I needed to hear, so thank you for your time and opinion!!! And no, you don’t sound cynical or dismissive!
A past doc advised doing this, but what you said is exactly where I’ve always landed with the decision. I’m always a little insecure about my choice due to ignoring the advice of a professional smarter than I am, and then it reared its ugly head again after understanding the 70%+ number and Claude scaring the bejesus out of me 
Realistically, the only thing I would do differently is force a statin to get my numbers even lower, but I’m not on one because they make me feel blah.
Once again, I will file this and go back to waiting for the Lp(a) lowering drugs.
Truly, thank you once again.
Please let us know @LukeMV once you have the pitavastatin vs rosuvastatin LDL and ApoB results I’m interested! 
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