Muscle pains and many non-specific effects occur in 1-20% of the people taking statins. Elevated liver enzymes within a limit of up to 3 time normal may occur in about

Very few in my experience. You can always reduce the statin dose and add bempedoic acid to the regimen--or you can add etzitamide or resins if bempedoic acid is too expensive.

Well, first off, In many cases statins aren't prescribed in their optimum dose (40mg in primary and 80 mg in secondary prevention). This may explain why i have seen very few patients developing statin intolerance.

I use statins at the minimum dose to get the maximal response with respect to stabilizing./regressing plaque. This sometimes requires the maximum dose of rosuvastatin oratorvastatin.

Myalgia and muscle pain Is less frequent in my experience. At a times replacement by Fluvastatin alivates the muscle pain.

William Feeman could you please share clinical efficacy in term of LDL reduction in primary & secondary prevention of bempedoic acid vs statins?

In other words, does bempedoic acid equally effective as statins in statin-intolerant patients?

William Feeman

Dear Zahid Mahmood, there is till today, to my knowledge no evidence about reduction of morbidity and mortality by using Bempedoic acid when uses as primary and secondary Prevention. While statin through its pleotrophic effect on blood vessels reduces both morbidity and mortality due to vascular disease.

Dear Dr Mahmood,

While I agree with Dr Ahmed's answer entirely, I would point out that bempedoic acid inhibits the enzyme in cholesterol synthesis just a few steps prior to the enzyme inhibited by statins, and so may have the same pleotropic effects as statins. Hence it should be used in statin intolerant patients, but bempedoic acid may not be as good as statins in LDL-c lowering, based on my own experience with the drug. Is this helpful?

Dear Dr William Feeman, at times although it look mechanistically two drugs are similar but RCT do not show similar outcome.Sir if there is any CVOT with bempedoic acid ?

Dear Andrei G Dan. Sir thanks for your vivid information right on the question. I want to add alittle :There is difference between eligibility of statin between North America and Europe due difference in coronary risk scores.The eligibility for statin is higher in North America because of use of statin for primary prevention.

Dear Dr Ahmed,

The bempedoic acid CVOT rial is called CLEAR Outcomes. It is not yet finished. I agree that bempedoic acid may not do all of the things that statins do. I have asked about liberating nitric acid at the arterial wall, but no one seems to know. Still, if one reduces the statin dose and adds bempedoic acid, lipid changes will be essentially unchanged with few myalgias.

Dear William Feemen, thank you so much for your information. Sir will you pl share few lines about your views as regard PCSK9.

In familial hypercholesterolemia, statins and bempedoic acid or resins or ezetimide (in younger patients only) may not allow patients to reach lipid target goals. PCSK-9 mab can allow the patient to reach goals but are expensive and inconvenient (bi-weekly or monthly injections). Inclisiran will be on the market soon and though it is expensive, a once or twice a year injection is much, much more convenient.

Thank you so much., William Feeman.Sir Does PCSK _9 mab gives additional CV protection independent of cholesterol lowering effect?

Not that I know of.

I have some good expieriences in patients with myalgia by reducing the frequency of administration of the very long acting rosuvastatin. Many patients with myalgia have good LDL cholesterol control with 2 doses p. week instead of daily dosing with complete disappearance of the myalgia.

I would like to thank William Feeman Chowdhury/Chaudhury Meshkat Ahmed Andrei G Dan

warm regards,

Zahid

You are most welcome. Peace.

Dear Zahid Mahmood, thanks goes to you for introducing such important question. It was great opportunity to have interaction with William Feemen. Who is an authority on lipid management and have published numerous articles related to cholesterol over last 3 decades.

Again, you are most welcome. Peace. By the way I will be doing two posters at the virtual EAS symposium in about 2 months. One is about angiographic changes in response to therapy and the other is about two patients of mine who reached 100 years of age taking their statins.

Almost all of the concerned studies have given it be anywhere between 15-20 % of patients who developed statins intolerance.

Dear Willy Verhiest,

Sir, very precious observation.

I have two confusion

2. If there is any different 'very long acting' Rosuvastatin or is it the usual one to be given at longer interval.

2.Althoigh there was good LDL control, do you have any concern about getting same pleotrophic effect that occurs with usual doses.

By the way, in some cases rosuvastatin can be given once a week.

I fully agree. The minimum dose of the statin to have a good control of LDL cholesterol must be determined on an individual basis by trial and error. I was often surprised that 10 mg rosuvastatin once or twice a week was enough for it.

Actually, in some cases 5 mg of rosuvastatin will do the job. The concept of doubling the dose of rosuvastatin and only giving it once as week--as opposed to 5 mg qod--is an interesting idea. Thank you for the idea.

dear colleague,

a negative expectation of the patient towards the drug, leads to an increase in the frequency of side effects. In particular for statins! It could be shown that myopathies, for example, only occur more frequently with statins than with placebo if the patient knows that he or she is taking a statin. An effect I observed myself. This has created dillemma for informed consent in my patients. To what extend should I talk about negative side effects, when initializing therapy?

Further evidence for the nocebo effect of statins is now provided by a group of researchers led by Frances Wood and Dr. James Howard from Imperial College London. In a letter to the editors of the "New England Journal of Medicine", the scientists report on an experiment they did with 60 patients who had discontinued statin therapy in the past because of side effects. Each participant was given four vials of atorvastatin tablets at a dose of 20 mg, with placebo tablets and without any contents. Over the following year, the subjects were asked to use one of the vials each month, in a randomly determined order. Meanwhile, they entered daily into a smartphone app whether they had side effects and rated the intensity of the symptoms on a scale from 0 (no symptoms) to 100 (worst imaginable symptoms).

The evaluation showed that 90 percent side effects under statin-verum also occurred under placebo. The average symptom intensity was 8.0 in the tablet-free months, 15.4 in the placebo months and 16.3 in the atorvastatin months!

I expected something, but not this much!

Regards

I frequently observed that myopathie occurs after some months of statin use, one month with a washout can mask this sideffect of long time use. I always informed my patients about it but if it occured by decreasing the dose, it could nearly always being kept under control.

Dear Willy Verhiest,

Sir your observations and experience on statin as regard myopathy is very appealing to me. Thank you so much.

Does same process of 'wash out: or' weekly dose' also use full in situations, where we have to stop statin for raised hepatic enzyme?

Dear Chowdhury-chaudhury-Ahmed,

In my 40 year experience I never had to stop statins because of hepatotoxicity. I have found that every patient needs a personal titration with the goal of reaching the recommended LDL cholesterol with the lowest possible dosage. I always start with the lowest dosage of a long acting statin (type rosuva - atorva) and titrated up or downwards. I was often surprised by the good control with once a week. There are no specific studies with once a week administration but reaching a safe target of LDL is important, not how you do it.