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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 5  |  Issue : 2  |  Page : 75-78

Frequency of rhabdomyolysis in patients treated with statins in hamad general hospital, Qatar


1 Department of Pharmacy, Hamad General Hospital, Doha, Qatar
2 Department of Accident and Emergency, Hamad General Hospital, Doha, Qatar
3 Department of Medicine, Hamad General Hospital, Doha, Qatar

Date of Submission01-Mar-2021
Date of Acceptance10-May-2021
Date of Web Publication23-Jul-2021

Correspondence Address:
Dr. Abdelmonem Badawi Yousif
Department of Pharmacy, Hamad General Hospital, P.O. Box: 3050, Doha
Qatar
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ljms.ljms_13_21

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  Abstract 


Background: Statins are well tolerated but associated with various statin-associated symptoms, including statin-associated rhabdomyolysis. Objectives: The aim of this study was to evaluate the frequency of rhabdomyolysis in patients treated with various statins and to describe their clinical features and outcomes in our local setting. Patients and Methods: This retrospective cross-sectional study was conducted at Hamad General Hospital and included all patients who received statins for the period between January 1, 2017, and November 31, 2017. Results: Out of 1000 cases involved in this study, 3 cases (0.3%) met the criteria for rhabdomyolysis. Two of them were males and the third was a female. Two cases received simvastatin and one case received rosuvastatin. All developed muscle pain and were hospitalized, during which all patients were treated with drug withdrawal and hydration. Upon discharge, rosuvastatin was replaced by atorvastatin, while simvastatins were replaced by atorvastatin and rosuvastatin. Conclusion: Rhabdomyolysis is a recognized but rare side effect of statins that should not be a reason to limit the use of life-saving statin therapy.

Keywords: Cyclosporin, gemfibrozil, rhabdomyolysis, statins


How to cite this article:
Yousif AB, Hassan EA, Ahmed MU, Lashin MS, Kunjumon NM, Sulaiman TO, Saliba M, Shier AA, Babikir MM, Saeed WA, Farghaly AA, Khan FY. Frequency of rhabdomyolysis in patients treated with statins in hamad general hospital, Qatar. Libyan J Med Sci 2021;5:75-8

How to cite this URL:
Yousif AB, Hassan EA, Ahmed MU, Lashin MS, Kunjumon NM, Sulaiman TO, Saliba M, Shier AA, Babikir MM, Saeed WA, Farghaly AA, Khan FY. Frequency of rhabdomyolysis in patients treated with statins in hamad general hospital, Qatar. Libyan J Med Sci [serial online] 2021 [cited 2021 Sep 27];5:75-8. Available from: https://www.ljmsonline.com/text.asp?2021/5/2/75/322200



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  Introduction Top


Controlled trials have shown that statins therapy is the cornerstone for the treatment of cardiovascular disease (CVD), with significant reduction in the morbidity and mortality.[1] Moreover, the ongoing researches are investigating the possible role of statins in the treatment of dementia, hypertension, diabetes mellitus, and arthritis. Therefore, an increasing number of patients are considered eligible to receive statins to reduce cardiovascular risk. In general, statins are safe and well tolerated,[1],[2] however, are associated with skeletal muscle, metabolic, neurological, as other possible side effects. These side effects are labeled as statin-associated symptoms because there is no consensus that statins are actually causal,[1] and most of this data are derived from case reports and observational studies, rather than controlled trials.[3]

Therefore, patients might discontinue statin therapy because of fears of side effects, which may or may not be treatment related, based on reports in the lay media or advice from inexperienced pharmacist, or friends or family members.[3] It is estimated that almost 30% of statin discontinuations occur within the 1st year of treatment and are most likely due to adverse side effects.[4] In a meta-analysis of 15 statin studies, patients taking 80% of their prescribed statin therapy had a 45% increase in all-cause mortality and a 15% increase in CVD accidents compared to patients who were more adherent.[5]

In Qatar, statins are one of the most widely prescribed medications, the side effect of which has not been well studied. Statin-associated rhabdomyolysis has only been described in a few case reports and in one study.[6],[7],[8] The aim of this study was to evaluate the frequency of rhabdomyolysis in patients treated with various statins and to describe their clinical features and outcomes in our local setting.


  Patients and Methods Top


This retrospective cross-sectional study was conducted at Hamad General Hospital and included all patients who received statins for the period between January 01, 2017, and December 31, 2017. The ethical approval was obtained from the research committee at Hamad Medical Corporation (# MRC-01-18-232).

This study involved all patients, 18-year-old or more, who received statins for at least 3 months, during the period of study, while patients with <18-year-old and those with incomplete medical records and with viral or autoimmune myositis were excluded from the study. A patient was classified as having rhabdomyolysis if the serum creatinine kinase (CK) was more than 10 times the upper normal limit (normal: 26–192 U/L).[9]

A sample size of 1000 participants was obtained, which provide a power of 80% at an α = 0.05, and the results were expressed as percentage, mean ± standard deviation, or median.


  Results Top


Of the 1000 patients who received statins, 548 (54.8%) were males and 452 (45.2%) were females. The mean age was 59.99 ± 11.25 years (range: 25–98 years). Diabetes mellitus was the most common associated comorbidity, representing 74.2% of all cases, followed by hypertension 729 (72.9%) and coronary artery disease 331 (33.1%). Rosuvastatin was the most commonly prescribed statin followed by atorvastatin. [Table 1] describes the demographic and clinical characteristics of patients enrolled in this study. Only 3 cases (0.3%) developed rhabdomyolysis during the period of study.
Table 1: Demographic and clinical characteristics of the patients involved in this study

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Characteristics of patients with rhabdomyolysis

Out of 1000 cases involved in this study, 3 cases (0.3%) met the criteria for rhabdomyolysis. Two of them were males and the third was a female. Two cases received simvastatin and one case received rosuvastatin. All developed muscle pain and were hospitalized, during which all patients were treated with drug withdrawal and hydration. Upon discharge, rosuvastatin was replaced by atorvastatin, while simvastatins were replaced by atorvastatin and rosuvastatin. [Table 2] describes the demographic and clinical characteristics of patients who developed statin-associated rhabdomyolysis.
Table 2: Demographic and clinical characteristics of the patients with statin-associated rhabdomyolysis

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  Discussion Top


With the expected increase in the number of patients who considered eligible to receive statins, clinicians and pharmacists should be aware of the side effect of these drugs on solid evidence to avoid unnecessary drug restriction or cessation and to provide more complete information to their patients regarding the prognosis of the condition.

Although rhabdomyolysis is a well-documented side effect of statin therapy, its incidence is not well known. The database of the Adverse Event Reporting System of the US Food and Drug Administration reported rates of statin-induced rhabdomyolysis of 0.3–13.5 cases per 1,000,000 statin prescriptions.[10] In a large clinical trial, statin-associated rhabdomyolysis was found in <0.5% of patients.[11],[12],[13],[14] Nevertheless, the incidence of statin-associated rhabdomyolysis is higher in practice than in controlled trials in which high-risk participants are usually excluded.[15]

In our study, the frequency of rhabdomyolysis was 0.3%, which is low and comparable with the above-mentioned figures. Our finding with others in the literature showed that the frequency of statin-associated rhabdomyolysis is low and does not justify the fear of prescribing this drug for eligible patients.

Factors that increase statin concentrations or reduced body muscle mass can increase the risk of statin-associated rhabdomyolysis by increasing the statin concentration in the muscles to produce symptoms.[16],[17] Lower plasma volumes and muscle mass are associated with advanced age, female sex, physical impairment, and a lower body mass index and are likely statin-associated rhabdomyolysis risk factors. Whereas increased statin concentration is associated with hypothyroidism, higher statins doses, concomitant use of drugs such as cyclosporin, and gemfibrozil that are inhibitors or substrates of CYP450, especially the 3A4 isoenzyme. Concomitant use of drugs and compounds with toxic muscle affects such as colchicine and alcohol can also increase the risk of statin-associated rhabdomyolysis.[1],[10],[15],[18] With few exceptions, such as two of our patients were males, and none of them alcoholic or had hypothyroidism, our patients' clinical characteristics were similar to that mentioned in the literature.

This American College of Cardiology/American Heart Association/National Heart, Lung and Blood Institute (ACC/AHA/NHLBI) recommendations include baseline monitoring of CK levels for all patients being initiated on statin therapy.[9],[19] Routine CK level monitoring is not recommended in all patients after beginning statin therapy but only in patients who develop muscle symptoms while on statin therapy.[1],[16] We observe that most of the patients enrolled in this study lack the baseline CK values.

The mainstay of treatment for statin-associated rhabdomyolysis is discontinuation of treatment and hydration to protect kidney function. Once the patient's muscle symptoms have subsided, clinicians have several options to treat that patient's dyslipidemia, including using a lower dose of the same statin, starting a different statin, and/or using lipid-lowering agents other than statins.[20] Similarly, statins were discontinued in our patients and different statins were initiated. The main limitation of this study is its retrospective design and being hospital based.


  Conclusion Top


Rhabdomyolysis is a recognized but rare side effect of statins that should not be a reason to limit the use of life-saving statin therapy. Inpatient and outpatient clinicians and pharmacists can be directly involved in monitoring drug safety and tolerability and should therefore be aware of the signs and symptoms of statin-associated rhabdomyolysis. Once the diagnosis is established, the management includes statin discontinuation and hydration, and upon recovery, re-initiation of different statins can be tried.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Nielsen SF, Nordestgaard BG. Negative statin-related news stories decrease statin persistence and increase myocardial infarction and cardiovascular mortality: A nationwide prospective cohort study. Eur Heart J 2016;37:908-16.  Back to cited text no. 3
    
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Chowdhury R, Khan H, Heydon E, Shroufi A, Fahimi S, Moore C, et al. Adherence to cardiovascular therapy: A meta-analysis of prevalence and clinical consequences. Eur Heart J 2013;34:2940-8.  Back to cited text no. 5
    
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Khan FY, Ibrahim W. Rosuvastatin induced rhabdomyolysis in a low risk patient: A case report and review of the literature. Curr Clin Pharmacol 2009;4:1-3.  Back to cited text no. 6
    
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Khan FY, Matter I, Alsamawi M, Lutf AQ. Rhabdomyolysis and hepatitis associated with pravastatin therapy. J Clin Diagn Res 2007;3:151-4.  Back to cited text no. 7
    
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Bener A, Dogan M, Barakat L, Al-Hamaq AO. Comparison of efficacy, safety, and cost-effectiveness of various statins in dyslipidemic diabetic patients. Indian J Pharmacol 2014;46:88-93.  Back to cited text no. 8
[PUBMED]  [Full text]  
9.
Pasternak RC, Smith SC Jr., Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant C. American College of Cardiology; American Heart Association; National Heart, Lung and Blood Institute. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. J Am Coll Cardiol 2002;40:567-72.  Back to cited text no. 9
    
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Davidson MH, Clark JA, Glass LM, Kanumalla A. Statin safety: An appraisal from the adverse event reporting system. Am J Cardiol 2006;97:32C-43C.  Back to cited text no. 10
    
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Dujovne CA, Chremos AN, Pool JL, Schnaper H, Bradford RH, Shear CL, et al. Expanded clinical evaluation of lovastatin (EXCEL) study results: IV. Additional perspectives on the tolerability of lovastatin. Am J Med 1991;91:25S-30S.  Back to cited text no. 12
    
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Boccuzzi SJ, Bocanegra TS, Walker JF, Shapiro DR, Keegan ME. Long-term safety and efficacy profile of simvastatin. Am J Cardiol 1991;68:1127-31.  Back to cited text no. 13
    
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Pedersen TR, Berg K, Cook TJ, Faergeman O, Haghfelt T, Kjekshus J, et al. Safety and tolerability of cholesterol lowering with simvastatin during 5 years in the Scandinavian Simvastatin Survival Study. Arch Intern Med 1996;156:2085-92.  Back to cited text no. 14
    
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Antons KA, Williams CD, Baker SK, Phillips PS. Clinical perspectives of statin-induced rhabdomyolysis. Am J Med 2006;119:400-9.  Back to cited text no. 15
    
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Schech S, Graham D, Staffa J, Andrade SE, La Grenade L, Burgess M, et al. Risk factors for statin-associated rhabdomyolysis. Pharmacoepidemiol Drug Saf 2007;16:352-8.  Back to cited text no. 16
    
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Banach M, Rizzo M, Toth PP, Farnier M, Davidson MH, Al-Rasadi K, et al. Statin intolerance-an attempt at a unified definition. Position paper from an International Lipid Expert Panel. Expert Opin Drug Saf 2015;14:935-55.  Back to cited text no. 17
    
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Chatzizisis YS, Koskinas KC, Misirli G, Vaklavas C, Hatzitolios A, Giannoglou GD. Risk factors and drug interactions predisposing to statin-induced myopathy: Implications for risk assessment, prevention and treatment. Drug Saf 2010;33:171-87.  Back to cited text no. 18
    
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Pasternak RC, Smith SC Jr, Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant C, et al. ACC/AHA/NHLBI Clinical advisory on the use and safety of statins. Stroke 2002;33:2337-41.  Back to cited text no. 19
    
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Harper CR, Jacobson TA. Evidence-based management of statin myopathy. Curr Atheroscler Rep 2010;12:322-30.  Back to cited text no. 20
    



 
 
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