A comprehensive review and meta-analysis of risk factors for statin-induced myopathy

Nguyen, Khoa A.; Li, Lang; Lu, Dongsi; Yazdanparast, Aida; Wang, Lei; Kreutz, Rolf P.; Whipple, Elizabeth C.; Schleyer, Titus

doi:10.1007/s00228-018-2482-9

Cited by 63 publications

(44 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Nonetheless, not every patient who is affected carries such polymorphisms. Studies have also demonstrated an effect of statin-induced myopathy on the disturbances in homeostasis of calcium, reduced cholesterol synthesis at the cellular level, and an increase in expression of HMG-CoA reductase inhibitors [6]. Another attribution of statin-induced myopathy is the part played by mitochondria, where a dysfunctional or decreased coenzyme-Q10 synthesis might play a role [7].…”

Section: Discussionmentioning

confidence: 99%

Features of Rhabdomyolysis Secondary to Immobility and Statin-Induced Myopathy in a 70-Year-Old Female

Shahid

Akbar

Ariff

2020

Cureus

View full text Add to dashboard Cite

Treatment with statins requires close monitoring of serum creatine kinase levels to prevent myopathy, which is a rare but potentially serious dose-dependent adverse effect of these drugs. Statins are cholesterol-lowering drugs that are among the most prescribed drugs worldwide and are considered effective in reducing the risk of major cardiovascular events. Although statins are generally well-tolerated, myopathies are a rare but known adverse event, ranging from muscle pain to very rare cases of life-threatening rhabdomyolysis. In this report, we aim to highlight the features of rhabdomyolysis secondary to immobility and statin-induced myopathy.

show abstract

Section: Discussionmentioning

confidence: 99%

Features of Rhabdomyolysis Secondary to Immobility and Statin-Induced Myopathy in a 70-Year-Old Female

Shahid

Akbar

Ariff

2020

Cureus

View full text Add to dashboard Cite

show abstract

“…The case reports presented in this review identified very well-known risk factors for rhabdomyolysis suspected to be due to macrolides-statins combination. Advanced age, cardiovascular diseases, renal impairment, DM, and concomitant interacting drugs are all considered risk factors for the development of statin-induced rhabdomyolysis with or without concomitant macrolides 57,70,71,83…”

Section: Discussionmentioning

confidence: 99%

“…In another review of case reports of statin-induced rhabdomyolysis, most cases of simvastatin-induced rhabdomyolysis occurred at a dose of 40 mg 71. Also, Nguyen et al found that the OR of developing simvastatin-induced rhabdomyolysis was significantly increased when the simvastatin dose was larger than 20 mg 70. Clarithromycin was the most suspected offending agent in more than 50% of the cases, followed by erythromycin, while azithromycin was implicated in only one case.…”

Section: Case Reports From the Literaturementioning

confidence: 99%

“…About 85% of the patients were ≥64 years old, of those about 54% were ≥75 years of age. In the literature, advanced age (65 years or older) is a risk factor for developing rhabdomyolysis with statin monotherapy 70. This risk will increase when combining statin with an interacting drug such as clarithromycin.…”

Section: Case Reports From the Literaturementioning

confidence: 99%

“…Interestingly, 38.5% of patients represented with gout. Cardiovascular diseases, especially hypertension, diabetes mellitus (DM), and renal insufficiency are considered as risk factors for developing statin-induced muscle toxicity 70,72. All patients with DM had also reported renal impairment, except in one case, which possibly makes DM-induced renal impairment the highest risk, not just DM.…”

Section: Case Reports From the Literaturementioning

confidence: 99%

See 2 more Smart Citations

<p>The clinical significance of statins-macrolides interaction: comprehensive review of in vivo studies, case reports, and population studies</p>

Mellal¹,

Hussain²,

Said³

2019

TCRM

View full text Add to dashboard Cite

The objectives of this article were to review the mechanism and clinical significance of statins-macrolides interaction, determine which combination has the highest risk for the interaction, and identify key patients’ risk factors for the interaction in relation to the development of muscle toxicity. A literature review was conducted in PubMed and Embase (1946 to December 2018) using combined terms: statins – as group and individual agents, macrolides – as group and individual agents, drug interaction, muscle toxicity, rhabdomyolysis, CYP3A4 inhibitors, and OAT1B inhibitors, with forward and backward citation tracking. Relevant English language in vivo studies in healthy volunteers, case reports, and population studies were included. The interaction between statins and macrolides depends on the type of statin and macrolide used. The mechanism of the interaction is due to macrolides' inhibition of CYP3A4 isoenzyme and OAT1B transporter causing increased exposure to statins. The correlation of this increased statin’s exposure to the development of muscle toxicity could not be established, unless the patient had other risk factors such as advanced age, cardiovascular diseases, renal impairment, diabetes, and the concomitant use of other CYP3A4 inhibitors. Simvastatin, lovastatin, and to lesser extent atorvastatin are the statins most affected by this interaction. Rosuvastatin, fluvastatin, and pravastatin are not significantly affected by this interaction. Telithromycin, clarithromycin, and erythromycin are the most “offending” macrolides, while azithromycin appears to be safe to use with statins. This review presented a clear description of the clinical significance of this interaction in real practice. Also, it provided health care professionals with clear suggestions and recommendations on how to overcome this interaction. In conclusion, understanding the different characteristics of each statin and macrolide, as well as key patients’ risk factors, will enable health care providers to utilize both groups effectively without compromising patient safety.

show abstract

Association of Statin Use With Risk of Liver Disease, Hepatocellular Carcinoma, and Liver-Related Mortality

et al. 2023

View full text Add to dashboard Cite

ImportanceGiven the burden of chronic liver disease on the health care system, more information on the hepatoprotective association of statins in the general population is needed.ObjectiveTo examine whether regular statin use is associated with a reduction in liver disease, particularly hepatocellular carcinoma (HCC) and liver-related deaths, in the general population.Design, Setting, and ParticipantsThis cohort study used data from the UK Biobank (UKB) (individuals aged 37-73 years) collected from baseline (2006-2010) to the end of follow-up in May 2021, from the TriNetX cohort (individuals aged 18-90 years) enrolled from baseline (2011-2020) until end of follow-up in September 2022, and from the Penn Medicine Biobank (PMBB) (individuals aged 18-102 years) with ongoing enrollment starting in 2013 to the end of follow-up in December 2020. Individuals were matched using propensity score matching according to the following criteria: age, sex, body mass index, ethnicity, diabetes with or without insulin or biguanide use, hypertension, ischemic heart disease, dyslipidemia, aspirin use, and number of medications taken (UKB only). Data analysis was performed from April 2021 to April 2023.ExposureRegular statin use.Main Outcomes and MeasuresPrimary outcomes were liver disease and HCC development as well as liver-associated death.ResultsA total of 1 785 491 individuals were evaluated after matching (aged 55 to 61 years on average, up to 56% men, and up to 49% women). A total of 581 cases of liver-associated death, 472 cases of incident HCC, and 98 497 new liver diseases were registered during the follow-up period. Individuals were aged 55-61 years on average, with a slightly higher proportion of men (up to 56%). In UKB individuals (n = 205 057) without previously diagnosed liver disease, statin users (n = 56 109) had a 15% lower hazard ratio (HR) for the association of developing a new liver disease (HR, 0.85; 95% CI, 0.78-0.92; P &lt; .001). In addition, statin users demonstrated a 28% lower HR for the association with liver-related death (HR, 0.72; 95% CI, 0.59-0.88; P = .001) and a 42% lower HR for the development of HCC (HR, 0.58; 95% CI, 0.35-0.96; P = .04). In TriNetX individuals (n = 1 568 794), the HR for the association of HCC was reduced even further for statin users (HR, 0.26; 95% CI, 0.22-0.31; P = .003). The hepatoprotective association of statins was time and dose dependent, with a significant association in PMBB individuals (n = 11 640) for incident liver diseases after 1 year of statin use (HR, 0.76; 95% CI, 0.59-0.98; P = .03). Taking statins was particularly beneficial in men, individuals with diabetes, and individuals with a high Fibrosis-4 index at baseline. Carriers of the heterozygous minor allele of PNPLA3 rs738409 benefited from statin use and had a 69% lower HR for the association with HCC (UKB HR, 0.31; 95% CI, 0.11-0.85; P = .02).Conclusions and RelevanceThis cohort study indicates substantial preventive associations of statins against liver disease, with an association with duration and dose of intake.

show abstract

A comprehensive review and meta-analysis of risk factors for statin-induced myopathy

Abstract: This comprehensive assessment of risk factors can help support clinicians in reducing the incidence of SIM in their patient population on statins.

Cited by 63 publications

References 44 publications

Features of Rhabdomyolysis Secondary to Immobility and Statin-Induced Myopathy in a 70-Year-Old Female

Features of Rhabdomyolysis Secondary to Immobility and Statin-Induced Myopathy in a 70-Year-Old Female

<p>The clinical significance of statins-macrolides interaction: comprehensive review of in vivo studies, case reports, and population studies</p>

Association of Statin Use With Risk of Liver Disease, Hepatocellular Carcinoma, and Liver-Related Mortality

Contact Info

Product

Resources

About