Inflammatory myositis (IM) presents a diagnostic challenge due to its multifaceted etiology and varying clinical presentations. This case involves a 55-year-old male with asymptomatic hypothyroidism, recent statin use, and rapidly progressing proximal muscle weakness. He presented with profound weakness in the upper and lower extremities, severely impairing his daily activities. The patient\'s medical history included recent hospitalizations for idiopathic interstitial lung disease, myopericarditis, and pneumonia, adding complexity to his condition. Laboratory findings revealed elevated serum muscle enzymes, notably creatine kinase, indicating muscle damage and rhabdomyolysis. Serological testing confirmed the absence of myositis-specific antibodies and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies. The patient was eventually diagnosed with IM and rhabdomyolysis, likely secondary to statin use or hypothyroidism. Treatment with methylprednisolone, levothyroxine, and discontinuation of atorvastatin led to rapid improvements in AST levels and overall muscle strength. This case highlights the challenges of managing IM and emphasizes the importance of assessing thyroid function before initiating lipid-lowering therapy.

Background: SLCO1B1 variants are known to be a strong predictor of statin-associated muscle symptoms (SAMS) risk with simvastatin. Methods: The authors conducted a retrospective chart review on 20,341 patients who had SLCO1B1 genotyping to quantify the uptake of clinical decision support (CDS) for genetic variants known to impact SAMS risk. Results: A total of 182 patients had 417 CDS alerts generated, and 150 of these patients (82.4%) received pharmacotherapy that did not increase risks for SAMS. Providers were more likely to cancel simvastatin orders in response to CDS alerts if genotyping had been done prior to the first simvastatin prescription than after (94.1% vs 28.5%, respectively; p < 0.001). Conclusion: CDS significantly reduces simvastatin prescribing at doses associated with SAMS.

Aim: The frequencies of SLCO1B1*5 and CYP2C9*2 and *3 in specific Asian, Native Hawaiian and Pacific Islander (NHPI) subgroups are unknown. Patients & methods: Repository DNA samples from 1064 women self-identifying as Filipino, Korean, Japanese, Native Hawaiian, Marshallese or Samoan and aged 18 years or older were used for targeted sequencing of three genetic variants (rs4149056, rs1799853 and rs1057910). Results: SLCO1B1*5 was significantly less frequent in NHPI women (0.5-6%) than in Europeans (16%). Except for Koreans, CYP2C9*2 (0-1.4%) and *3 (0.5-3%) were significantly less frequent in all subgroups than in Europeans (8 and 12.7%, respectively). Prior reports showed that Asian and NHPI individuals have significantly higher ABCG2 Q141K allele frequency (13-46%) than Europeans (9.4%). Combined phenotype rates for rosuvastatin and fluvastatin revealed that Filipinos and Koreans had the highest frequencies of statin-associated myopathy symptoms risk alleles. Conclusion: Differences in ABCG2, SLCO1B1 and CYP2C9 allele frequencies among different racial and ethnic subgroups highlight the need for increased diversity in pharmacogenetic research. Risk alleles for statin-associated myopathy symptoms are more prevalent in Filipinos, underscoring the importance of genotype-based statin dosing.
Statins are medications used to lower low-density lipoprotein (‘bad’) cholesterol. Variation in genes for proteins which transport drugs (SLCO1B1 and ABCG2) or metabolize drugs (CYP2C9) may significantly influence how much statin someone is exposed to. Genetic variants within SLCO1B1 can affect exposure to all statins, while variants within ABCG2 and CYP2C9 can affect exposure to rosuvastatin and fluvastatin, respectively. The prevalence of the decreased or no-function genetic variants is unknown among Filipino and Native Hawaiian and Pacific Islander (NHPI) subgroups. The major racial categorization of ‘Asians and NHPI’ (ANHPI) can miss potential genetic and ancestral differences among population subgroups. Our study used biobank data from 1064 women of ANHPI descent to estimate the frequencies of four important variants within SLCO1B1, ABCG2 and CYP2C9. Those of ANHPI ancestry were less likely to have variations in SLCO1B1 and CYP2C9 but significantly more likely to have nonfunctional ABCG2 than Europeans. Our findings provide insight into SLCO1B1 and CYP2C9 genetic variations among under-represented subgroups. Specifically, Filipinos and Koreans have the highest rates of higher risk genetic variants linked to high rosuvastatin and fluvastatin exposure and muscle-related side effects. Estimating the frequency of genetic variations in under-represented subgroups is pivotal in reducing health disparities in treatment outcomes, diversifying pharmacogenetic research and advancing personalized medicine.

Statins are known to pharmacologically target 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Several subtypes of anti-HMGCR autoimmune myopathies have been reported as a result of statin use. Although these types vary widely, a severe and rare form of statin-induced myopathy is immune-mediated necrotizing myopathy (IMNM), resulting in severe muscle injury that does not respond to statin cessation and is associated with poor outcomes. Diagnosis is confirmed through biopsy confirming the necrosis of biopsy fibers, in addition to elevated anti-HMGCR serum levels. Management lacks proper guidelines, however, immunosuppressive therapy has been proposed as a possible intervention. The aim of this report is to increase providers\' knowledge of the presentation and possible treatment of statin-induced immune-mediated necrotizing myopathy.

The efficacy of statins in the primary and secondary prevention of cardiovascular disease has been proven beyond doubt. The number needed to treat to prevent one cardiovascular event is 1 in 30 over 10 years, and the number needed to treat for secondary prevention is much lower. However, a recent study demonstrated that only 68% of eligible patients are on statin therapy. Moreover, there seems to be a reluctance to escalate statin doses due to the fear of adverse effects. The adverse effects that worries patients and their physicians most frequently are those related to muscular symptoms. N-of-1 trial evidence suggests that muscular symptoms attributed to statins are often caused by the nocebo effect. This article aims to provide a structured, evidence-based approach to suspected statin-related muscle toxicity.

Atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality, and statins have become a cornerstone in its treatment and prevention. Despite the well-documented benefits of statins, many patients stop taking them, with adverse muscle symptoms being a commonly cited reason. Although some statin-associated adverse muscle effects are real, some can be attributed to the nocebo effect, which is the patient\'s perception of harm. The purpose of this article is to review the literature on statin safety, particularly that related to muscle, to analyze adverse effects, and to propose various treatment strategies for the statin intolerant patient.

To provide a systematic approach to management of the patient with statin-attributed muscle symptoms.
We examined the prevalence of statin intolerance, the role of the nocebo effect, key findings in the patient\'s history and laboratory studies, the potential value of coronary calcium scoring, and the importance of shared decision-making in considering statin re-initiation. Most patients with statin-attributed muscle symptoms can be successfully treated with statins or a combination of statins and non-statins to achieve successful ASCVD risk reduction.

BACKGROUND: Although low vitamin D levels are associated with statin-associated muscle symptoms (SAMS), it remains unclear if vitamin D supplementation leads to symptom improvement.
OBJECTIVE: We performed a systematic review to evaluate the association of vitamin D supplementation with resolution of SAMS.
METHODS: We searched Medline (PubMed), Embase and Cochrane Library till 12 December 2021. Full length articles that reported on the association between vitamin D supplementation in adult patients with SAMS were included.
RESULTS: We identified 8 interventional studies comprising 669 participants. Majority of the participants were of Caucasian ethnicity and the mean age of participants ranged from 59.5 to 64.8 years old. The studies recruited patients with initial mean pre-treatment vitamin D levels ranging from 17.8 to 22.0ng/mL. Follow up duration ranged from 2 to 24 months and mean post-treatment vitamin D levels ranged from 34.3 to 56.0ng/mL. We found that vitamin D supplementation was associated with improved statin tolerance in 509 out of 606 (83.9%) patients across the 7 studies which reported patient numbers after supplementation (95% CI = 0.81-0.87, I2 = 72% n = 7). None of the studies were randomized controlled trials (RCTs) and hence placebo effect of vitamin D could not be ruled out. Nocebo effect of statin was also not assessed by any of the studies.
CONCLUSIONS: Vitamin D supplementation in patients with mild-moderate vitamin D insufficiency was associated with improvement of SAMS. However, quantitative efficacy analysis was not possible and this observed association is likely confounded by nocebo and placebo effects. RCTs are required to conclusively assess the utility of vitamin D supplementation in improving SAMS.

OBJECTIVE: Statins are essential medications in the treatment of atherosclerotic cardiovascular disease; however, remain widely underutilized in large part due to concerns regarding adverse side effects. We describe the role of the nocebo effect in the perception of statin intolerance and provide management recommendations utilizing both statin and non-statin lipid-lowering therapies.
RESULTS: The recent Self-Assessment Method for Statin side-effects Or Nocebo (SAMSON) trial demonstrated that 90% of adverse symptoms related to statins were also elicited by placebo, a powerful demonstration of the nocebo effect. Importantly, 50% of the study patients were able to successfully reinitiate statin therapy. Statin intolerance is common and can often be managed with expectation setting and adjustment of doses and/or dosing regimens. In those who remain unable to tolerate statins, numerous alternative lipid-lowering therapies exist with strong safety and efficacy profiles.

There is a well-validated association between SLCO1B1 (rs4149056) and statin-associated muscle symptoms (SAMS). Preemptive SLCO1B1 pharmacogenetic (PGx) testing may diminish the incidence of SAMS by identifying individuals with increased genetic risk before statin initiation. Despite its potential clinical application, the cost implications of SLCO1B1 testing are largely unknown. We conducted a cost-consequence analysis of preemptive SLCO1B1 testing (PGx+) versus usual care (PGx-) among Veteran patients enrolled in the Integrating Pharmacogenetics in Clinical Care (I-PICC) Study. The assessment was conducted using a health system perspective and 12-month time horizon. Incremental costs of SLCO1B1 testing and downstream medical care were estimated using data from the U.S. Department of Veterans Affairs\' Managerial Cost Accounting System. A decision analytic model was also developed to model 1-month cost and SAMS-related outcomes in a hypothetical cohort of 10,000 Veteran patients, where all patients were initiated on simvastatin. Over 12 months, 13.5% of PGx+ (26/193) and 11.2% of PGx- (24/215) participants in the I-PICC Study were prescribed Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline-concordant statins (Δ2.9%, 95% CI -4.0% to 10.0%). Differences in mean per-patient costs for lipid therapy prescriptions, including statins, for PGx+ compared to PGx- participants were not statistically significant (Δ USD 9.53, 95% CI -0.86 to 22.80 USD). Differences in per-patient costs attributable to the intervention, including PGx testing, lipid-lowering prescriptions, SAMS, laboratory and imaging expenses, and primary care and cardiology services, were also non-significant (Δ- USD 1004, 95% CI -2684 to 1009 USD). In the hypothetical cohort, SLCO1B1-informed statin therapy averted 109 myalgias and 3 myopathies at 1-month follow up. Fewer statin discontinuations (78 vs. 109) were also observed, but the SLCO1B1 testing strategy was 96 USD more costly per patient compared to no testing (124 vs. 28 USD). The implementation of SLCO1B1 testing resulted in small, non-significant increases in the proportion of patients receiving CPIC-concordant statin prescriptions within a real-world primary care context, diminished the incidence of SAMS, and reduced statin discontinuations in a hypothetical cohort of 10,000 patients. Despite these effects, SLCO1B1 testing administered as a standalone test did not result in lower per-patient health care costs at 1 month or over 1 year of treatment. The inclusion of SLCO1B1, among other well-validated pharmacogenes, into preemptive panel-based testing strategies may provide a better balance of clinical benefit and cost.