Uncovering the Relationship Between Statins and Muscle Problems in the ELSA-Brasil MSK Cohort.

PURPOSE: To investigate the association between statins and muscle problems in a highly diverse sample of Brazilian civil servants. METHODS: We conducted a cross-sectional data analysis at baseline of the ELSA-Brasil MSK cohort. Pain was identified through self-reported symptoms in large muscle groups (lower back and/or hips/thighs). Muscle strength was assessed using the five-times-sit-to-stand (FTSTS) and handgrip tests, with weakness defined as the lowest and highest quintiles of age- and sex-stratified handgrip strength and FTSTS performance time, respectively. Multivariable logistic regression analyses were conducted to investigate the association between statin use and muscle pain and weakness. Secondary analyses explored the impact of different types of statins and their duration of use on the response variables. RESULTS: A total of 2156 participants (mean age 55.6 ± SD 8.9, 52.8% women) were included, of whom 21.1% were taking statins and 25.1% reported muscle pain. We found no significant association between statin use and muscle problems. Secondary analysis on different types of statins revealed an association between atorvastatin and muscle weakness, as measured by the five-times-sit-to-stand test (OR 1.94, 95% CI 1.12-3.37), but not by the handgrip test (OR 0.75, 95% CI 0.29-1.42). No evidence was found to support a link between the duration of statin treatment and muscle problems. CONCLUSIONS: This study challenges previous claims of an efficacy-effectiveness gap between experimental and observational literature on statins. The findings indicate that statin use does not contribute to muscular problems.

Comparative Muscle Tolerability of Different Types and Intensities of Statins: A Network Meta-Analysis of Double-Blind Randomized Controlled Trials.

PURPOSE: The benefits of statins for ischemic cardio-cerebrovascular diseases are well known. However, concerns around muscle adverse events still exist. We therefore aimed to compare the muscle safety of individual statins in adults. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials and Web of Science were searched to include double-blind randomized controlled trials (RCTs) comparing one statin with another or with control treatment. Pairwise meta-analyses and network meta-analyses were undertaken with Stata 14.0 software. Relative risk (RR) with 95% confidence intervals (CIs) was adopted for each outcome. RESULTS: A total of 83 RCTs were included. In the pairwise meta-analysis, statins were significantly associated with only a slight increase in muscle symptoms compared with control (RR=1.05; 95% CI=1.01-1.09). In the drug-level network meta-analyses, no statistically significant difference was found between individual statins in the incidence of muscle symptoms, myalgia, myopathy, rhabdomyolysis, creatine kinase (CK) >10 times the upper limit of normal (ULN) or discontinuation due to muscle adverse events. In the dose-level network meta-analyses, there were no statistically significant dose-dependent effects on any outcomes except that moderate-intensity statins had a higher incidence of muscle symptoms than control (RR=1.13; 95% CI=1.01-1.27). Moderate simvastatin (RR=6.57; 95% CI=1.26-34.41) and moderate pravastatin (RR=5.96; 95% CI=1.00-35.44) had a statistically significantly higher incidence of CK >10×ULN compared with moderate atorvastatin. Lipophilic statins and statins metabolized by liver cytochrome P450 3A4 were not associated with an increased risk of muscle adverse events. CONCLUSION: Statins may be generally safe on muscle. Moderate atorvastatin may be superior to equivalent simvastatin and pravastatin in muscle tolerability.

Neuromuscular Complications of Statin Therapy.

PURPOSE OF REVIEW: This review provides an overview of neuromuscular side effects associated with statin use, their diagnosis, and treatment. RECENT FINDINGS: The discovery of anti-HMGCR antibodies led to a better understanding of clinical aspects of statin-associated anti-HMGCR myopathy and its treatment. Statins are widely prescribed medications with well-established benefits in the treatment of cardiovascular diseases and stroke. Adherence to statins is influenced by development of side effects, especially muscle related. There is wide range of neuromuscular side effects associated with statin therapy. Documented neuromuscular side effects include asymptomatic elevation of muscle enzymes, mild-moderate myalgias and cramps, toxic and immune-mediated severe necrotizing myopathy, and rare cases of rhabdomyolysis. In addition, statins can lead to unmasking or triggering of underlying muscle and neuromuscular junction disorders. This article identifies the risk factors and provides a review of neuromuscular side effects associated with statin use, their diagnosis and treatment.

A pilot study on the association between SLCO1B1 RS4363657 polymorphism and muscle adverse events in adults with newly diagnosed dyslipidaemia who were prescribed a statin: the Malaysian primary health care cohort.

Introduction: Statin, the first-line treatment for dyslipidaemia, may have suboptimal adherence due to its associated muscle adverse events. These data, however, remain limited. Aim: To determine the association of serum creatine kinase (CK) and SLCO1B1 rs4363657 polymorphism with statin-associated muscle adverse events (SAMAE) among dyslipidaemia participants. Methods: This was a prospective cohort study at government health clinics involving newly diagnosed adults with dyslipidaemia. SAMAE were recorded based on the patient's complaint after a month on statin. CK was taken at baseline and follow-up. Genetic profiling was performed for SLCO1B1 rs4363657 polymorphism. Results: Among 118 participants, majority were Malay (72%) males (61%) with a mean age of 49 ± 12.2 years old and prescribed lovastatin (61.9). There was a significant association between statin types (lovastatin and simvastatin) and SAMAE (p = 0.0327); no significant association noted between CK and SAMAE (p = 0.5637). The SLCO1B1 rs4363657 polymorphism was significantly associated SAMAE (p < 0.0001). Conclusions: In this first pilot study of a multiethnic Malaysian population, the incidence of SAMAE was 18.6%. SAMAE were significantly higher in subjects on lovastatin compared to simvastatin. SLCO1B1 rs4363657 polymorphism was a significant risk factor for SAMAE.

The Impact of Red Yeast Rice Extract Use on the Occurrence of Muscle Symptoms and Liver Dysfunction: An Update from the Adverse Event Reporting Systems and Available Meta-Analyses.

Red yeast rice (RYR) has a cholesterol-lowering effect due to the presence of bioactive components (monacolins, mainly monacolin K) that act by inhibiting the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The European Food Safety Authority (EFSA) assessed the use of RYR and, while pointing out several uncertainties regarding the available data, raised a warning related to the safety of RYR when used as a food supplement at a dose of monacolin as low as 3 mg/day. In their decision in June 2023, EFSA approved the use of monacolins from RYR at doses less than 3 mg/day. We therefore decided to interrogate the different adverse event reporting systems (FAERS and CAERS) and analyse the characteristics of the cases reported to be associated with RYR supplements, and we reviewed the most recent meta-analyses with a focus on the occurrence of muscle symptoms and liver dysfunction. In terms of all musculoskeletal disorders from September 2013 (when the first case related to RYR consumption was recorded) to 30 September 2023, 363,879 cases were reported in the FAERS, with the number of cases related to RYR consumption being very small and accounting for 0.008% of cases. In the same time frame, 27,032 cases of hepatobiliary disorders were reported, and the cases attributable to RYR ingestion accounted for 0.01% of all cases. A low rate of muscle symptoms and liver dysfunction attributed to RYR ingestion was also observed in the CAERS database, where only 34 cases of adverse muscle events and 10 cases of adverse liver events reported RYR as the suspect product, while 19 cases of both muscle events and 10 cases of adverse liver events reported it as a concomitant product. This profile mirrors that of meta-analyses of randomised clinical trials of RYR, in which RYR use was not associated with either liver dysfunction or muscular adverse symptoms.

Statin use in patients with non-HMGCR idiopathic inflammatory myopathies: A retrospective study.

BACKGROUND: Statins are the most widely used lipid lowering therapies which reduce cardiovascular risk, but are associated with muscular adverse events (AEs). Idiopathic inflammatory myopathies (IIM) are autoimmune diseases of the muscle with higher risk of cardiovascular disease. More data is needed regarding statin safety in patients with intrinsic muscle disease such as IIM. HYPOTHESIS: Statins are tolerated in patients with IIM without leading to significant increase in muscular AEs. METHODS: Statin use was retrospectively examined in a longitudinal IIM cohort. Safety analysis included assessment of muscular and nonmuscular AEs by chart review. IIM patients receiving a statin during the cohort follow-up period were matched to IIM patients not receiving a statin for comparative analysis of longitudinal outcomes. RESULTS: 33/214 patients had a history of statin use. 63% started for primary prevention, while others were started for clinical ASCVD events, vascular surgery, IIM related heart failure, and cardiac transplantation. A high intensity statin was used in nine patients with non-HMGCR myositis, and tolerated in 8/9 patients. Statin related muscular AE was noted in three patients. There were no cases of rhabdomyolysis, or statin related nonmuscular AEs in a median observation period of 5 years. In patients newly started on statins during cohort follow-up (n = 7) there was no change in disease activity after statin initiation. Long term outcomes were not different between statin and nonstatin IIM control groups. CONCLUSION: Statins were well tolerated in patients with non-HMGCR positive IIM. Given the accelerated atherosclerotic risk in IIM patients, further prospective studies of statin safety in IIM patients are warranted.

An assessment by the Statin Muscle Safety Task Force: 2014 update.

The National Lipid Association's Muscle Safety Expert Panel was charged with the duty of examining the definitions for statin-associated muscle adverse events, development of a clinical index to assess myalgia, and the use of diagnostic neuromuscular studies to investigate muscle adverse events. We provide guidance as to when a patient should be considered for referral to neuromuscular specialists and indications for the performance of a skeletal muscle biopsy. Based on this review of evidence, we developed an algorithm for the evaluation and treatment of patients who may be intolerant to statins as the result of adverse muscle events. The panel was composed of clinical cardiologists, clinical lipidologists, an exercise physiologist, and a neuromuscular specialist.