Frequency of Myalgias in Patients taking Statins Treatment of Dyslipidemia

Objectives: To study the frequency of statin induced myopathy in patients presenting with hyperlipidemia on statin therapy. To study the comparison between Rosuvastatin and Atorvastatin induced myopathy. It was a descriptive study at Medical Department of Pakistan Institute of Medical Sciences, Islamabad from Jun-Dec 2015.

Material and Method: 150 cases of hyperlipidaemia were selected. Patients of 25-75 years of age and both sexes, with BMI of up to 25, having hyperlipidemia and on statin therapy for more than one week regardless of type or dose of statins, were included in the study. Patients having BMI>25, presenting with cardiac disease, diabetes mellitus, Hypertension, Hyper/Hypothyroidism, Nephrotic Syndrome, addict of alcohol or smoker were excluded from the study.

Result: In our study 110 patients were found to have hypercholesterolemia, 116 were having hyper-triglyceridemia and 40 patients were having low HDL-C levels. Out of the population with hypercholesterolemia 37 were male and 73 were female, with triglyceridemia 34 were male and 82 were females. 15 out of 150 patients (10%) developed statin induced myopathy.02(3.2%) developed statin induced myopathy in Rosuvastatin group, 5(11.3%) developed statin induced myopathy in Atorvastatin group and 8(27.3%) developed statin induced myopathy in Simvastatin group.

Conclusion: We concluded that significant proportion of our population having dyslipidemias when treated with statins, developed myopathy. Furthermore, least cases of myopathy were induced by rosuvastatin and most by simvastatin.

Key Words: Hyperlipidemia; Statins; Myopathy; Triglyceridemia; Myalgias;

Received: Oct’2020   Accepted: Nov.2020




Cardiovascular diseases is a largely preventable, major cause of morbidity and mortality, food, obesity, and atherosclerosis promote cardiovascular risk. Adapting to healthy eating, exercise, quitting smoking, avoiding alcohol, treating diabetes, hypertension, and hyperlipidemia demote the risk. Hyperlipidemia is defined as “high levels of total cholesterol, low density lipoprotein cholesteroland/ or low levels of high density lipoprotein (HDL) cholesterol”. Hyperlipidemia is a serious well proven, modifiable risk factor for atherosclerotic coronary artery disease in all ethnic groups, ages and both gender. Adults with no risk factors for cardiovascular disease should have their fasting lipid profile test once every five years.1,2 Risk increases with a higher level of LDL cholesterol (promotes atherosclerosis) and a lower level of HDL cholesterol3. Reducing cholesterol prevents atherosclerotic coronary artery disease and in patients with prior myocardial infarction or stroke, reduces recurrence and the need for revascularization.4 Reducing LDL cholesterol by 1 mmol/l lowers cardiovascular risk by 22%.


Significant proportion of our population having

dyslipidemias, when treated with statins, developes

myopathy. Furthermore, female gender

was more likely to have statin induced myopathy

than male gender and rosuvastatin has the

least common side effect of myopathy.


HMG-CoA reductase inhibitors (Statins) are widely used to decrease lipid levels and reduce morbidity and mortality related to cardiovascular disease.. Statins are recommended by most international guidelines for both primary and secondary prevention of cardiovascular diseases. Statins benefitted all patients regardless of age, race, pre-existing hypertension, and even patients with normal cholesterol reducing morbidi ty and mortality. Statins reduce the production of LDL cholesterol by 20-50% and statins pleiotropic effect stabilizes the atherosclerotic plaque5. Statins use, despite being effective, have some unfavorable side effects that lead to poor compliance. The most common(72%) of these side effects are muscle related. Myotoxicity presents in four ways in the form of myalgia, myopathy with asymptomatic elevation of creatinine phosphokinase, myositis, and rhabdomyolysis.6 Statin induced myalgia depend upon type and potency of statins, and interactions with other drugs like antibiotics and other lipid-lowering drugs7. Statin associated myalgia are also seen more frequently in elderly females may be because of low BMI, and with co-morbidities like diabetes, hypertension, and hypothyroidism. We need to study what role statins play in the development of these symptoms and how important it is to rule out this treatable cause in our society before labelling and treating these as non-specific aches and pains. Moreover, patients who discontinue the drugs because of side effects are identified and offered alternative lipid-lowering drugs and strategies to reduce cardiovascular risk. We are currently experiencing a higher prevalence of cardiovascular diseases further research is warranted on this topic.8,9 So mass efforts are needed in Pakistan to counter this growing epidemic of cardiovascular diseases




This descriptive study was conducted in General Medicine Outpatient Department of Pakistan Institute of Medical Sciences (PIMS), Islamabad, from 6/6/16 to 6/12/16. The study was approved by ethical committee of the institute. Informed consent from all participants was taken. A total of 150 patients of each gender between 25-75 years of age were included. 52% of patients were below 50 years of age. Female to male ratio was (1.7:1). Patients with hyperlipidemia, on statin therapy for more than one week, regardless of type and dose of statins, who presented with muscular pains, were included in the study, using non probability consecutive sampling. Patients with diabetes mellitus, hypertension, cardiac disease, BMI>25, alcohol addicts, nephrotic syndrome or smokers were excluded from the study. A complete fasting lipid profile was obtained after an overnight fast (8-12 hours). History including presence and duration of myalgia, dose and duration of statin therapy, were taken from each study subject. Examination was also done, with special emphasis on signs of myopathy like muscle tenderness and lipid abnormalities like exanthemas and xanthelasmas. Hyperlipidaemia was diagnosed according to ESC (European Society of Cardiology) guidelines. ECS consensus panel suggests that muscle symptoms which start with initiation of statin and disappear with discontinuation and reappear on re-initiation are defined as statin associated muscle symptoms.14 Myalgia are defined as pain in muscle or a group of muscles with normal levels of serum creatinine.10 The data was analyzed with the help of statistical package for social sciences version (SPSS 16) Information from pro forma was converted to variables. Quantitative variables including age, CPK, LDL-C, HDL-C, Cholesterol and Triglycerides were presented by mean +/- SD. Percentages and frequencies were calculated for qualitative variables for example, gender and categories of LDL-C, HDL-C, Total Cholesterol and Triglycerides. Effect modifiers like age and gender were controlled by stratification. Post stratification chi-square test was applied. P value < 0.05 was considered as significant.




Data regarding weight, height and BMI was calculated as mean and standard deviation. Patients had an average weight of 52 to 75 kgs , average height of 15.3 to 179.6 cms and average BMI 19 and 24.7.



The lipid profile of the patients was analyzed using descriptive statistics. The mean +/- SD cholesterol level was 176.7 +/- 56.7 gm/dl. Similarly, average triglyceride level was 181.7 +/= 117.1 gm/dl. The average high density lipoprotein was 34.2 +/= 10.9 gm/dl in our study while low density lipoprotein was 105.9 +/- 50.2 gm/dl. The distribution of hypercholesterolemia and hyper-triglyceridemia were measured using the standard cutoff value of >200 mg/dl. In our study 110 (73.3%) were found to have hypercholesterolemia and 116(77.3%) were having hyper-triglyceridemia. The frequency of HDL-C and isolated HDL-C were calculated as per study objective. We found out that majority of the patients 102 (93.3%) were having low HDL-C levels. Similarly, 95 patients (86.7%) of the study population had isolated low HDL-C. 82 patients (74.6%) had high levels of LDL. Though not our primary aim, we also calculated the distribution of the lipid profile according to the gender of the study patients. Out of the population with hypercholesterolemia, 37 (68.5%) were male and 73(76%) were female, with hyper-triglyceridemia, 34(63%) were male and 82(85.5%) were females. However, gender distribution was quite different among low HDL-C and isolated low HDL-C groups. It was found the out of 54 patients, 48(88.8%) male population was having low HDL-C level compared to 90(93%) females. On the other hand, isolated low HDL-C was more common in male population 42(77.7%) in comparison to females 84(87.5%). In our setting we used three statins that were freely available in our setting. 64(42%) patients were taking rosuvastatin, 49 (32%) patients were taking atorvastatin, 37(26.6%) were taking simvastatin. Among the study patients, 02(3.2%) developed statin induced myopathy in Rosuvastatin group, 5(11.3%) developed statin induced myopathy in Atorvastatin group and 8(27.3%) developed statin induced myopathy in simvastatin group. So statin induced myopathy was most common in simvastatin group and least common in rosuvastatin group.



In our study we also concluded that statin induced myopathy was more common in females 11(11.7%) and less common in males 4(7.1%).




We found out that patients with hyperlipidaemia and on statin therapy, 15 out of 150 patients (10%) developed statin induced myalgia with a higher frequency in females. Highest incidence was with simvastatin and least with rosuvastatin. Similar studies are done in different parts of the world. Hilmer and Smith et al concluded that the most severe adverse effect of statins is myotoxicity, in the form of myopathy, myalgia, myositis and rhabdomyolysis.11,12 These side effects depend upon type and potency of statins, gender of patients, and interactions with other drugs and even exercise as studied by scholars around the world.13 Statin therapy greatly reduces the risk of cardiovascular disease but because of its side effect in the form of myopathy, we are unable to fully benefit from its use.14,15 Beth et al defined, statin induced side effects as SAMS (statin associated muscle symptoms) and also proposed that this should be treated by decreasing dose or using alternative statins or using alternative treatment for lipid lowering.16 Statin induced myalgia is a common side effect in Pakistani population maybe because of their genetic makeup for which further studies and evaluation needs to be done. A study was conducted in Lahore by Saleha et al, which showed prevalence of myalgia with statin more in females as compared to males just like our conclusion. However, in their study they could show that regardless of myalgia being more common in females, the CPK levels were raised more in males.17 We couldn’t follow CPK levels because of financial constrains and that limited our study only to statin induced myalgia. Not everyone came to the same conclusion. A study done in Lahore showed that prevalence of statin induced myalgia in Pakistani population is much less as compared to our results.18 A few studies around the world contradict our study because they claim that statins don’t cause any muscle symptoms on their own but only in the presence of vitamin D deficiency.19 There were a few limitations in our study. Majority of the OPD patients had multiple co-morbids, which put them at increased risk of myalgia and therefore had to be excluded from the study. Vitamin D deficiency has also been proven in dif ferent studies as a factor worsening statin induced myalgia15, but it was not possible for us to check Vit D levels because of its high price. Another limitation was that a lot of patients did not follow up so had to be excluded. Increased incidence of statin induced myopathy, has negatively affected its tolerability by high risk patients. Our study can increase awareness regarding statin induced myopathy, among patients who are at high risk of cardiovascular disease and need lipid lowering therapy. To realize that statins can be the cause of myalgia in patients coming to OPDs, can have a positive impact on patients’ compliance, as alternative drug can be started, drug interactions be avoided, alternative day treatment can be tried to minimize risk of cardiovascular disease.19,20,21 More awareness needs to be created in our part of the world regarding this issue and also efforts need to be made to manage this debilitating side effect of statins.22




We conclude that significant proportion of our population having dyslipidemias, when treated with statins, developed myopathy. Furthermore, we found out that female gender was more likely to have statin induced myopathy than male gender and Rosuvastatin has the least common side effect of myopathy.

1. Robinson JG, Stone NJ. The 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk: a new paradigm supported by more evidence. European heart journal. 2015;36(31):2110-8.

2. Anderson TJ, Grégoire J, Hegele RA, Couture P, Mancini GJ, McPherson R, et al. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Canadian Journal of Cardiology. 2013;29(2):151-67.

3. Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, et al. Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society consensus panel statement on assessment, aetiology and management. European heart journal. 2015;36(17):1012-22.

4. Mohassel P, Mammen AL. Statin associated autoimmune myopathy and anti HMGCR autoantibodies. Muscle & nerve. 2013 Oct;48(4):477-83.

5. Parker BA, Thompson PD. Effect of statins on skeletal muscle: exercise, myopathy, and muscle outcomes. Exercise and sport sciences reviews. 2012;40(4):188.

6. Tomaszewski M, St?pie? KM, Tomaszewska J, Czuczwar SJ. Statin-induced myopathies. Pharmacological reports. 2011;63(4):859-66.

7. Jacobson TA, Ito MK, Maki KC, Orringer CE, Bays HE, Jones PH, et al. National lipid association recommendations for patient-centered management of dyslipidemia: part 1—full report. Journal of clinical lipidology. 2015;9(2):129-69.

8. Hilmer S, Gnjidic D. Statins in older adults. Australian Prescriber. 2013;36(3):79-82.

9. Page SR, Yee KC. Rhabdomyolysis in association with simvastatin and dosage increment in clarithromycin. Internal medicine journal. 2014;44(7):690-3.

10. Smith J. Appropriate primary prevention of cardiovascular disease: does this mean more or less statin use? Australian Prescriber. 2011;34(6):169-72.

11. Thompson PD, Parker BA, Clarkson PM, Pescatello LS, Michael White C,Grimaldi AS, et al. A randomized clinical trial to assess the effect of statins on skeletal muscle function and performance: rationale and study design. Preventive cardiology. 2010 ;13(3):104-11.

12. Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, et al. Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society consensus panel statement on assessment, aetiology and management. European heart journal. 2015;36(17):1012-22.

13. Mancini GJ, Baker S, Bergeron J, Fitchett D, Frohlich J, Genest J, Gupta M, et al. Diagnosis, prevention, and management of statin adverse effects and intolerance: proceedings of a Canadian Working Group Consensus Conference. Canadian Journal of Cardiology. 2011;27(5):635-62.

14. Joy TR, Hegele RA. Narrative review: statin-related myopathy. Annals of internal medicine. 2009;150(12):858-68.

15. Ganga HV, Slim HB, Thompson PD. A systematic review of statin-induced muscle problems in clinical trials. American heart journal. 2014;168(1):6-15.

16. Santos PC, Soares RA, Nascimento RM, Machado-Coelho GL, Mill JG, Krieger JE, et al. SLCO1B1 rs4149056 polymorphism associated with statin-induced myopathy is differently distributed according to ethnicity in the Brazilian general population: Amerindians as a high risk ethnic group. BMC medical genetics. 2011;12(1):136.

17. Singh H, Chakrawarti A, Guruprasad P, Singh H, Gupta YK. Difference in occurrence of muscle-related adverse effects of statins among male and female geriatric patients: A crosssectional observational study. Nigerian Postgraduate Medical Journal. 2016;23(4):202.

18. Mengal MN, Zahid SA, Ashraf T, Badini AM. frequency of adverse events associated with statin use in routine clinical practice in pakistani population. Pakistan Heart Journal. 2017 Oct 25;50(2).

19. Michalska-Kasiczak M, Sahebkar A, Mikhailidis DP, Rysz J, Muntner P, Toth PP, Jones SR, Rizzo M, Hovingh GK, Farnier M, Moriarty PM. Analysis of vitamin D levels in patients with and without statin-associated myalgia—a systematic review and meta-analysis of 7 studies with 2420 patients. International journal of cardiology. 2015 Jan 15;178:111-6.

20. Joy TR, Hegele RA. Narrative review: statin-related myopathy. Annals of internal medicine. 2009 Jun 16;150(12):858-68.

21. Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, Roden M, Stein E, Tokgözo?lu L, Nordestgaard BG, Bruckert E. Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society consensus panel statement on assessment, aetiology and management. European heart journal. 2015 May 1;36(17):1012-22.