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Owen Linder, MD, FACP

Internal Medicine

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August 2025

Owen Linder ,MD, FACP

Here is anonymized data on the effect of coenzyme Q 10 on patients treated for hyperlipidemia with statin drugs. These patients all have coenzyme Q ten and genome CYP450 2D6 assays.

My interest began in 2009. At that time I cared for a hyperlipidemic patient who developed rhabdomyolysis. It is one of the most severe of adverse effects of statin drugs

The illness began after prescribing a statin drug for her hyperlipidemia. I observed her muscle fasciculations and elevated CPK after that  prescription. The treatment as I read about it in a textbook at the time was oral coenzyme Q ten, as well as cessation of the statin drug.  Current literature is largely focused on supportive measures with hydration for renal toxicity and muscle toxicity but with infrequent recent recommendations for the use of Coenzyme Q ten. (CoQ ten is also called Ubiquinone.)

Coenzyme Q10 is an essential and universal human cellular constituent. It is the obligatory coenzyme in the transfer of electrons within mitochondria. The transfer of electrons from the lower state of adenosine diphosphate to the higher energy state of adenosine triphosphate. This enables the KREBs cycle of energy production in the mitochondria.

As interest in statin toxicity has grown, we now  have a recent, very broad and deep summary about the use of ubiquinone for muscle pain; Zhuangqi Shi and Shuxin Han in a journal Heliyon published in  January 2025, state, “9 previous clinical trials assessed the effect of CO Q 10 supplementation on statin -induced muscle symptoms , with 5 showing beneficial effects and the other 4 showing no effect[138-146].”(citation #5) The ambivalence in the literature was double checked by an OPENEVIDENCE artificial intelligence search.

My compilation of data resolves the ambivalence of the conclusions  in the previous  studies.

My pathway:

In my treating hundreds of patients with statins, patterns of adverse effects came to my attention. I began making assays of the coenzyme Q ten blood levels to correlate with the adverse effects  and as a guide to alleviate the adverse effects in the individual patients. The first compilation was titled Cramps in Seniors, written in 2011(citation #1).

The earlier way in which adverse effects were defined was muscle pain with elevated CPK, or liver function tests ten times upper limit normal. (See citation #10 )

The setting of the threshold this high was dismissive of statin prescription only associated with muscle pain  without enzyme elevation.  This clinically obtuse dismissal was echoed at the last  (2025)  American College of Physicians annual meeting in a lecture by a doctor holding post as  head of a university cardiology department.

However now there are authors taking this issue seriously. This sector has researched the issue and evolved to confer greater credence to clinical symptoms even without signs or biochemical changes. [Citation #7 Hirota and citation #10].  As early as 2011 I got complaints of muscle cramps from many people on statins. Often the pain of limbs in patients on statin is described as quick onset, very painful, muscle cramps. Often the cramps occur in the evening after strenuous exertion.

Titration of coenzyme Q ten given as a prescription with resulting resolution of the patients’ complaints of cramps (regardless of absence of  rise in CPK nor physical findings) followed by assays of it assured me I was treating in an effective way which tracked with the blood levels.

More recent background:

In 2023 I became aware that other professionals had been correlating statin adverse effects to certain genomes.  After looking at those findings involving genomes, to consider  their findings I looked at the laboratory genomes available to my patients. The availability to them is circumscribed because they are enrolled  in one health maintenance organization. (HMO). This HMO controls lab access and reimbursement  by means of an enrollment contract sanctioned by Medicare. The genomes tested in the other study are  SLCO1B1, ABCG2, and CYP 450 2C9. ( citation # 2) The former two genomes create transporter proteins. Only the third creates a metabolizer protein in the liver.

The first two of these genome tests are unavailable to Labcorp patients in 2024-2025. In my pursuit of genomic relevance, I looked at the genomes which were readily available to Labcorp patients. The available genomes are CYP450 2D6, CYP450 2C9, and CYP450 2C19.

Importance of this study:

No one has published a longitudinal compilation of the coenzyme Q ten blood assays correlated with this group of genomes. In the spread sheet (available upon request or attached) one can see  the lower value Coenzyme Q ten assay; and the highest Coenzyme Q ten assay of each of 41 patients. The lower assays found before prescribing Coenzyme Q ten are generally unsupplemented levels.

In general prescribed doses of Coenzyme Q ten result in higher assays . The spread sheet shows the final therapeutic dose of Co Q ten and the change in Coenzyme Q ten assay levels. Unlike a formal study done in a set time frame these patients were repeatedly interviewed blood sampled over the years they were given medical care. The prescription of Coenzyme Q ten was titrated for alleviation of cardinal symptoms, muscle discomfort or memory distraction: or the adverse effect of Coenzyme Q ten , uncomfortable constipation.

I observe short term memory distraction is often correlated with Coenzyme Q ten depletion. When there is Coenzyme Q ten blood assay depletion there is memory distraction which resolves with Coenzyme Q ten replenishment. Memory dysfunction is seen in another column in the spread sheet.

Genomes correlating with need for replenishment:

 I prefer to use the term replenishment not supplementation. This term  is based on the sustained increase in blood assay level while the person is under statin and Coenzyme Q ten prescription. Since the coenzyme Q ten dose is titered up until symptom relief plateaus no matter how  short or long it takes, the term replenishment seems more descriptive of the intentional process than rote supplementation, to me.

Genomes are set at the inception of  life. Both parental DNAs contribute to a genome and the subunits called alleles (and if the alleles do not confer normal metabolism they are called polymorphisms). In this compilation the one genome of greatest correlation to coenzyme Q ten replenishment is CYP 450 2D6.

Replenishment is signified by the difference between earliest and the later, ie the highest coenzyme Q ten assays.  The genome appears to be CYP 450 2D6; not CYP 450 2C9 nor CYP 450 2C19. The spread sheet and statistical analysis show how the results by genome stack up.

However I note a different observation cited by Zhuangqi Shi (#5), “Rosuvastatin is metabolized by CYP 2C9 and transported by transporters such as OATP1B1 and BCRP…”  Shi wrote this on his or her page 8 section 4.6.

Contrary to Shi's observation, Hirota says rosuvastatin is unaffected by inhibition by either CYP ( referring to P450 CYP 3A4 and CYP 2C9).  And Hirota writes on the third page of his lengthily supported article:  ” Although the effects of the metabolic pathway of rosuvastatin cannot be excluded as a mechanism of interaction with rosuvastatin, the contribution of CYP 2C9 metabolism to rosuvastatin is minimal… And then in his paragraph 11 titled expert opinion; “Among statins, rosuvastatin was considered to show fewer drug -drug interactions because its pharmacokinetics were either independent of or only slightly affected by CYP enzymes.”…further clinical studies are important. “(citation #7)

Both authors offer opinions on rosuvastatin metabolism either via CYP 450 2C9 or not. My study  elucidates  assays  on CYP 450 2D6 and CYP 450 2C9 genes and both genes’ polymorphisms. This compilation provides the genomes and alleles of 42 of the paired Coenzyme Q ten patients. It provides their clinical signs to provide granular data.

I suspect a stronger set of correlations of slow or no processing alleles with CYP450 2D6 genomes. And I think even prior to statistical analysis, there are correlations of changes in coenzyme Q ten assays, and with improvement in clinical effects. The clinical effects are  muscle symptoms and distracted memory focus. We will run the correlations of other statins and of rosuvastatin with these genomes’ alleles.

The hundreds of biochemical articles used in the articles just named in citations #5,  & #7 are assays of the amount of such and such statin measured under the curve when mixed with other drugs in vitro. These are pharmacokinetic studies.

However this study is longitudinal and in vivo;  incorporating human complaints tracked over long periods and correlated with  markers of end points. The end points being reduction of  hyperlipidemia. The end points are successful reduction of cholesterol and LDL at or close to levels considered protective against atherosclerotic disease. The intermediate markers along the way to successful reduction of lipids have been replenished levels of coenzyme Q ten. Important to the patients the end points are reached without limitation by side effects of statins.

The genomes affect the processing of a statin in the hepatic enzyme systems. Many medicines are processed in the hepatic enzymes' systems. (citation #3)

Some genomes of some persons have variant alleles (polymorphisms)(citation #6). The variant alleles of interest have either slow or no processing capacity in hepatic enzyme systems for statin drugs.(citation #3).

Data Compilation

This compilation contributes some data to the relevance of CYP 450 2C9 and CYP 450 2D6.

Here is the data on this CYP 450 2C9  distribution of alleles among the patients tested:

The number of variant alleles of CYP 450 2C9 is a lesser percentage of the patients. Labcorp CYP 450 2C9 gene interpretation says alleles *2,*5, *8, and *11 have decreased function. It says *3,*6, and *13 have no function.

The number of subjects with any one of these low or no function alleles is  18. The total number of alleles among 65 patients is 130, for each gene separately. 130 alleles among CYP450 2C9 & 130 alleles among CYP 450 2D6.

The number of subjects with decreased function alleles *2 or *11 is 13. We  have paired Co Q ten assays in 7 of the 13.

Of these 5 of 7 have a large delta, replenishment of Coenzyme Q ten.

 

All five have low or desirable low density lipoprotein, LDL,  on statin treatment.

Two subjects have both alleles abnormal , one *2 and *3: the other two *2. There were no Co Q ten assays obtained from either patient.

Having 18 of 66 patients with gene CYP 450 2C9 with one or two slow or no processing alleles of 132 alleles may be too few  to support attribution of an effect on statin processing. Of the 18 patients with abnormal alleles the number with paired coenzyme Q ten assays is  seven..

Diagram

Here is a diagram of this set of information on patients with CYP 450 2C9 alleles

Column one                                column two                             column three

No function                                reduced function                  normal function

eight patients                             thirteen patients                    The remaining 47 patients

                                                                                                      with ninety normal  alleles

Number with a                          Number with a                      Number with a

pair of CoQ10 assays               pair of CoQ10 assays           pair of CoQ10 assays

six                                                   eight                                          twenty nine

                                        2C9 continued:

Of the 47patients with one or two normal function alleles there are 29 in whom to correlate pairs of Co Q ten assays.

Of the 21 patients with no or one diminished function allele there are 14 in whom to correlate pairs of coenzyme Q ten assays.

Having only found fourteen patients in total I am deferring  a breakdown by statin, dependent or not on hepatic metabolism.

CYP 450 2D6:

One may observe in the column of genomes on the data display spread sheet a predominance of variant alleles of genome CYP 450 2D6. This collection of 42 patients with paired coenzyme Q ten assays  had a total of 51 abnormal  alleles. The total of alleles normal and not normal is eighty four.

And in a collection of all 66 patients from whom genomes were assayed including 24 without paired coenzyme Q ten assays: the total number of alleles is 132. The number of abnormal alleles is 51  of those who had two or more CoQ ten assays; and the eight, who did not have a second CoQ ten assay. This gives a total of 59 abnormal alleles out of 132 . This means 45% of all the alleles are abnormal processing in the CYP450 2D6 genes .

Here is content for a grid of the items excluding patients without a gene study or without two coenzyme Q 10 assays;

Column one                                Column two                                                        Column three

No function alleles:                 Decreased function alleles                                                        Normal function alleles:

*3, *4, *5, *6,*7,*8,                *9, *10,*14, *17,                                    *1, *2, *35, *53

*11, *12, *13, *15,                   *29, *36+*10, *41

 *31, *36, *40, *42, *68         *49, *59

No function in either allele   decreased function in both alleles                                                        normal function in both alleles

Eight                                              none                                                        seven

No function in one allele       diminished function in one allele                                                        normal function in one allele

Twenty three                              sixteen                                                        twenty nine

                                                       

 Other reviewers said; “Regarding the role of CYP 2D6 in statin metabolism, it’s contribution to statin pharmacokinetics remains unclear [52]. However , numerous publications have demonstrated the impact of genetic variants such as *3,*4,*5, *10, *14,  and *41 [50],[53],[54] on impairing the metabolism of simvastatin and its metabolites. Despite this, to our knowledge there is a lack of research investigating the correlation between all previously mentioned CYP 2D6 gene variants and potential alterations in statin response as only CYP 2D6 *4 and *3 have gathered attention of researchers.”(citation#4).

CYP 2D6 research:

The data contributing to closing the gap in research of the effect of CYP 450 2D6 will follow

In my opinion the information on clinical and human characteristics comprise the phenotype of the polymorphic nature of genotypes of CYP2D6.

In one column I have calculated the difference between lowest and highest Coenzyme Q ten assays. In the 42 patients for whom I have two or more assays the average increase is about three fold (x2.8). This three fold increase was also found in the prior series of a different 44 patients in 2011(citation #1). Five of the first 44 are still in my group for 2025, 14 years later.

Of these five persons the average increase in Coenzyme Q ten assays was 3.68 times the first assay..

Emphasizing the value of this assay to their healthcare allowed me to direct patient attendance to a laboratory phlebotomy station at least twice, for two separate assays of Coenzyme Q ten.  Based on the Labcorp findings the alleles deemed by Labcorp to provide  normal metabolism of medications in the liver are *1,*2,*35, and *53. Twelve patients had only these normal rate of metabolism processing alleles.

Ten of the twelve had pairs of Co Q ten assays. The distribution is displayed in the spread sheet.

66 patients had a set of 3 gene assays for the contractually available genes.

Of the 66, 40 had one abnormal slow processing allele in the CYP 450 2D6 genome.

Of the same 40 patients 32 eventually had at least two assays of Co Q ten. In other words,  among this subset of 32 patients, with pairs of Co Q ten assays, each had one slow processing allele. The distribution is displayed in the spread sheet.

Also, among the 66 patients on whom genes were determined twelve had both alleles abnormal. Of this group of twelve, 8 had a pair of CoQ ten assays available for correlations. The distribution is displayed in the spread sheet.

So 40 patients had one slow processing allele and twelve had two slow processing alleles 30+12= 52 genomes with either one or two slow processing alleles.

This leaves 66-52= 14 patients with both alleles of CYP 450 2D6 of normal processing rate.

The potential import of this analysis in general is discussed in  Pharmacogenomics: Driving Personalized Medicine. Citation #9. And an example of the import in another medical field is shown  in the following paragraph from the National Colon Cancer Network Clinical Practice Guidelines in Oncology citation #8 It demonstrates the kind of reasoning which prescribers of statins could apply if genomic alleles were ascertained.

“A reduced starting dose of fluoropyrimidines is recommended for intermediate metabolizers (those who are heterozygous for DPYD decreased/no function variants). Some patients with decreased/no function variants tolerate normal doses of fluoropyrimidines; thus the CPIC Guidelines recommend increasing doses in subsequent cycles for patients with minimal or no toxicity in the first 2 cycles of treatment. Further dose reduction is recommended for those who do not tolerate the reduced starting dose. For those classified as poor metabolizers, the CPIC Guidelines recommend avoiding fluoropyrimidines.

These guidelines reflect common sense dose adjustments rather than methodically derived dosing based on actual pharmacokinetics. “ (citation #8).

 

Proposed frequentist analysis:

We will correlate the presence of abnormal alleles, zero, one, or two, with the pairs of Co Q ten assays. A frequentist  analysis of the spread sheet allows comparisons of slow processing alleles with the  CoQ ten assays. This analysis shall correlate the relative frequency of degree of rises in Co Q ten with the frequency of either zero, one, or two, slow processing alleles.

This frequency in turn can be correlated with the  clinical adverse effects of statins;

For example, the final tolerated dose of statin and the achievement of therapeutic levels of lipids. We need to correlate the likelihood of having zero, one, or two slow processing alleles with the likelihood of low rises in serum coq ten assays  with the likelihood of statin side effects and with the likelihood of cardioprotective lipid levels.

A practical hypothesis: 

The beneficial lipid levels were reached when statin side effects were overcome with doses of coenzyme Q ten. Previous studies were limited dose & time trials and without these correlations . I question the relevance of measuring the area under the curve of statin metabolism in vitro, ie pharmakokinetics.

Although finding the long term in vivo effects of statin requires a great deal of investigator staying power I think both this pilot study focusing on CYP 450 polymorphisms and  more paired controlled studies to come will be more helpful to understanding this subject.

This assertion upends the modern orthodoxy to treat all patient with diabetes for their lipids. The orthodoxy lacks consideration of a genotype disposing the patient to statin side effects. In this distribution of side effects of statins in 45% of patients the expectable clinical phenotype arising from slow processing alleles is a very good reason to treat with low doses of statins, if any. Knowing the genotype eliminates the mystery of why statin therapy ends up not reasonable for a lot of people.

The  presence of abnormal alleles can be correlated with levels of assays of Coenzyme Q ten (both low levels and delta pairs). This is turn can be correlated with the adverse effects of statins including muscle discomforts such as cramps, or tremors; or distracted short term memory .

Rosuvastatin:

The reasoning for displaying rosuvastatin doses in a separate column is because only this statin is among the statins in use in this practice not metabolized in hepatic enzyme systems. But to be fair see (citation #5).

Rosuvastatin was described as going  into the liver without going through a  hepatic transformation. (Citation # 7).  So I have followed the implication of variant alleles in CYP 450 2D6. The variant alleles may or may not affect the effect of rosuvastatin . Nor, I infer, does rosuvastatin greatly  affect the induction of depletion of Coenzyme Q ten. Thus there is less need for Coenzyme Q ten replenishment to alleviate statin adverse effects. Again a frequentist analysis will assign the explanatory power of this hypothesis.

An Illustration of utility:

For illustration of the potential use of metabolic processing rapidity, in the spread sheet of clinical findings, (available on request or included), line 50 is for person “SM”. She had post exertional leg cramps as a child. As an adult she had been on simvastatin 20 mg, many years before her entry to this practice in 2017. Her cramps upon exertion were worse since prescription of  simvastatin.

After entering this practice she had progressively less frequent and less intense leg cramps as her dose of coenzyme Q ten was increased up to 800 mg a day by 2023.

Her genomic analysis of CYP 450 2D6 revealed alleles *1  and *4. *1 has normal processing of medications. *4 allele function is characterized by slow processing  of medications in the liver. (citation #3)

Parenthetical note: The head of Labcorp genetics is going to be approached to quantify the slowness of metabolism. This includes statin drugs.

The statin mechanism of action  is inhibition of hepatic hydroxymethylglutaryl Coenzyme A reductase,  (abbreviated HMG CoA reductase.) This inhibition diminishes production of cholesterol and Coenzyme Q ten. The metabolic pathway is the mevalonate pathway. HMGCoA reductase inhibits the mevalonate pathway.(citation #3). Summing up clinical effects of statins is the phenotype of an individual. It is the result of the mevalonate pathway detailed by assignment of individual effects 1) the reduction in Coenzyme Q ten until replenished.

2) the lowering of cholesterol and Low Density Lipoproteins whilst a balance in the person is sought with 1) and 2).

3) repair of memory disorder until balance is achieved with 1) and 2)

Most statins are metabolized in the liver  into a follow on biochemical form of the statin before inhibiting HMGCo A reductase.( citation #7). This includes simvastatin.

Despite patient “SM” having a very useful replenishment dose of coenzyme Qten, 800mg, reflected by a high assay of serum Coenzyme Q ten : 3.4 mg/liter she still had some exertional and post exertional cramps in her calves. I think having one allele causing slow metabolism of simvastatin gave rise to the toxic effect of the drug in her muscles. The common interpretation in the literature is the high amount of simvastatin caused less Coenzyme Q ten to reach the cellular mitochondria. (Citations # 3 & #4 {double check})

My working diagnosis was a relative deficiency in coenzyme Q ten due to the potency of simvastatin 20 mg  three nights a week.. Evidence of this potency lie in the complete remission of cramps when  simvastatin’s potency was replaced with rosuvastatin 5 mg nightly more selective activity.

Her LDL remained the same. IE the degree of blockage of lipid production by HMGCoA reductase was the same. On simvastatin 20 mg 3 evenings a week in 2024 LDL was 85; on rosuvastatin 5mg nightly  in 2025 LDL was 81.

The difference was the slower processed metabolism of simvastatin, and the accumulation of simvastatin metabolites causing a more prolonged and more intense effect on the mevalonate pathway. The productions of cholesterol and LDL were  inhibited  by simvastatin and rosuvastatin.  But the  rosuvastatin activity  is not affected by the slow processing of *4 allele of CYP450 2D6 genome. Or not as affected.

In other words production of Coenzyme Q ten was more inhibited by simvastatin than rosuvastatin. Co Q ten was being replenished. Lipids were not replaced. Rosuvastatin worked effectively enough to lower LDL but was not affected by the slow metabolic allele of 2D6. Same person different responses based on different medications and possibly different alleles. citation #4.

The percentage of persons in the cohort collected in my practice with at least one slow processing alleles of genome CYP 2D6 is 80%.  I will statistically correlate the persons with alleles of subnormal processing with those members of the group's quantity of rise  in the blood level of coenzyme Q ten after replenishment.

Owen Linder, MD, FACP

1.      Cramps in Seniors, Pinellas County Medical Journal 2011

2.The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin -Associated Musculoskeletal Symptoms in Clin Pharmacol Ther, 2022 May , 111(5): 1007-1021 doi; 10.1002/cpt.2557 Epub2022 Mar 11 by Rhonda M. Cooper-DeHoff and twenty other coauthors PMID 35152405

3. “ Cytochrome P 450 2D6 is a drug metabolizing enzyme involved in the metabolism of more than 65 clinically important drugs including some….”  Laboratory Corporation of America Holdings, Weidong Huang, MD PhD Director Monogram Biosciences

4. Biomedicine & Pharmacotherapy 170 (2024) 115966 Available online 7 December 2023.  0753-3322/© 2023 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC By license (http://creativecommons.org/licenses/by/4.0/).Review. 
When the same treatment has different response: The role of pharmacogenomics in statin therapy Edward Zheng 1, Paulina Madura 1, Jakub Grandos 1, Marlena Broncel , Agnieszka Pawlos , Ewelina Wo´zniak , Paulina Gorzelak-Pabi´s * Dept. of Internal Diseases and Clinical Pharmacology, The Laboratory of Tissue Immunopharmacology, Medical University of Lodz, Poland

5.Personalized statin therapy: Targeting metabolic processes to modulate the therapeutic and adverse effects of statins by Zhuangqi Shi and Shuxin Han      Heliyon 11 (2025)e41629.

6. “An allele[1] is a variant of the sequence of nucleotides at a particular location, or locus, on a DNA molecule.[2]” Wickipedia definition

7. Takeshi Hirota, Yuito Fujita & Ichiro Ieiri (2020) An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins, Expert Opinion on Drug Metabolism & Toxicology, 16:9, 809-822, DOI: 10.1080/17425255.2020.1801634

Dr. Hirota wrote on page 817, "Stain-related muscle toxicity is particularly difficult to treat because there are no validated biomarkers  or tests that can be used to confirm patient self reports of statin related skeletal muscle toxicity, ...The most commonly used biomarker is creatine Kinase (CK) , a marker of muscle damage, but statin -related muscle toxicity can occur in the absence of clinicallly elevated CK."

Dr Hirota cites footnotes 161 and 162. his footnote 161 is Rosenson R Setal An assessment by the statin muscle safety task force:2014 update. J Clin Lipidol, 2014; 813 suppl) 558-71. and his #162 Mancini GBL et al. Diagnosis, prevention, and management of statin adverse effects and intolerance. Canadian consensus working group update (2016)Can J Cardio 2016; 32 (7 suppl) ;535-65.

8.Colon Cancer, Version 3.2024 NCCN Clinical Practice Guidelines in Oncology, Journal National Comprehensive Cancer Network 2024 , 22(2D):June 2024 e240029 "A reduced starting dose of fluoropyrimidines is recommended for intermediate metabolizers (those who are heterozygous for DPYD decreased/no function variants). …. For those classified as poor metabolizers, the CPIC Guidelines recommend avoiding fluoropyrimidines.  These guidelines reflect common sense dose adjustments rather than methodically derived dosing based on actual pharmacokinetics."

9 Sadee W, Wang D, Hartmann K, Toland AE. Pharmacogenomics: Driving Personalized Medicine. Pharmacol Rev. 2023 Jul;75(4):789-814. doi: 10.1124/pharmrev.122.000810. Epub 2023 Mar 16. PMID: 36927888; PMCID: PMC10289244.

10 , Review Int J Rheum Dis . 2024 Sep;27(9):e15337. doi: 10.1111/1756-185X.15337. Statin-associated muscle symptoms: A comprehensive exploration of epidemiology, pathophysiology, diagnosis, and clinical management strategies Meera Shah  1 , Karun Shrestha  2 , Chih-Wei Tseng  3   4 , Aman Goyal  5 , Teerin Liewluck  6 , Latika Gupta  7   8

Affiliations

PMID: 39285637 DOI: 10.1111/1756-185X.15337

Abstract

Statins are the first line of treatment for both primary and secondary prevention of atherosclerotic cardiovascular disease. Despite the positive effects of statins on cardiovascular events, not all patients can use them at an optimized dose. The reason for this is the skeletal muscle side effects, termed statin-associated muscle symptoms (SAMS). Despite extensive research, the precise pathophysiology of SAMS remains unclear and multiple mechanisms may contribute to this phenomenon. Various therapeutic options are available for the management of SAMS, ranging from rechallenging with the same or a different statin to utilizing non-statin therapeutic alternatives in patients intolerant to statins. However, the lack of consensus on the definition of SAMS, the absence of a definitive diagnostic test, and lack of a universally accepted management algorithm pose a great challenge in dealing with this entity. This review aims to explore the various pathophysiological mechanisms involved in SAMS and understand the difference between self-limited toxic myopathy and immune-mediated myopathy requiring immunomodulatory therapy. The conundrum of statin withdrawal, tapering, and rechallenge in SAMS will also be explored in detail along with the newer non-statin therapies that are available.

Keywords:

IMNM; SAMS; anti‐HMGCR; rechallenge; self‐limited statin myotoxicity; toxic myopathy.

© 2024 The Author(s). International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd. PubMed Disclaimer

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