Search Results (8)

Background and Objectives: Muscle symptoms are the most visible adverse event attributed to statins, but terminology is often imprecise. Most patients report myalgia or nonspecific aches, whereas objective myopathy, inflammatory or necrotizing myositis, rhabdomyolysis, and anti-HMGCR immune-mediated necrotizing myopathy are uncommon and clinically distinct entities. To provide a clinically oriented narrative synthesis of statin-associated muscle symptoms (SAMS) and severe statin-associated myotoxicity, and to propose a practical prevention, evaluation, and management algorithm. The classification of muscle events is used to standardize terminology and avoid diagnostic confusion, not to create a new formal taxonomy. Materials and Methods: A clinically oriented narrative review was performed using PubMed, Google Scholar, and major society documents published from January 2021 to April 2026. Eligible sources addressed SAMS, statin myopathy/myositis, rhabdomyolysis, anti-HMGCR immune-mediated necrotizing myopathy, nocebo/drucebo effects, pharmacogenetics, drug interactions, diagnosis, or management. The final evidence set comprised 55 verifiable sources, including blinded randomized or n-of-1/crossover evidence; meta-analyses; clinical statements and reviews; pharmacovigilance analyses; pharmacogenetic guidance; mechanism-focused reviews; anti-HMGCR series; and lipid-lowering guideline/treatment studies. Because the review was narrative, no pooled estimate or formal PRISMA screening log was generated. Results: Blinded evidence indicates only a small absolute excess of muscle pain with statins, concentrated mainly in the first year of therapy, and that most muscle symptoms reported during statin therapy are not pharmacologically caused by the statin. N-of-1 and crossover trials show that symptom intensity is often similar during statin and placebo periods, consistent with an important nocebo/drucebo contribution. Severe muscle toxicity can nevertheless occur, especially when systemic statin exposure is increased by a high dose, interacting drugs, frailty, renal or hepatic impairment, hypothyroidism, transporter or metabolic genotypes, or intense unaccustomed exercise. Statin choice matters chiefly through dose, pharmacokinetics, and interaction burden. Conclusions: SAMS are common as reported clinical problems, but confirmed statin-caused muscle injury is substantially less frequent than routine clinical attribution suggests. Permanent discontinuation should be reserved for carefully assessed cases. A structured approach—baseline risk assessment, selective CK measurement, exclusion of alternative causes, correction of modifiable risks, dechallenge/rechallenge, statin switching, dose reduction, and combination with non-statin therapy—preserves cardiovascular benefit while protecting the rare patient with genuine toxicity. Full article

Background: Solute carrier organic anion transporter family member 1B1 (SLCO1B1) mediates statin uptake into hepatocytes, the primary sites of cholesterol production. While the impact of SLCO1B1 variation on statin-associated muscle symptoms (SAMS) is well-documented, its role in LDL-C reduction remains understudied. This single-center, retrospective cohort study evaluated whether SLCO1B1 variation affects statin effectiveness in 213 adults. Methods: The SLCO1B1 variant rs4149056 (NM_006446.5:c.521T>C) was tested to categorize patients by their SLCO1B1 function: normal, decreased, or poor. The primary endpoint was percent change in LDL-C from baseline to follow-up (≥6 weeks post-statin initiation), with secondary endpoints of SAMS occurrence and statin adherence. Results: Overall, the average LDL-C decreased by 32% across all groups. No significant difference in LDL-C reduction was observed between SLCO1B1 phenotypes (p = 0.24). Conclusions: SLCO1B1 variation did not significantly affect LDL-C reduction, SAMS occurrence, or statin adherence. However, the retrospective design and limited adherence data in this study represent important limitations warranting prospective validation studies. Full article

Background and Aims: Statin-associated muscle symptoms (SAMS) is a frequent side effect of statin therapy, limiting its clinical use and increasing cardiovascular risk. Its relationship with muscle performance and quality is not completely understood. The aim of our study was to retrospectively assess the differences between body composition and muscle strength in patients with SAMS, compared with matched controls. Material and Methods: cardiovascular risk factors, lipid profile, and body mass index (BMI), were analyzed in 148 statin-intolerant (SI) and in 145 sex- and age-matched statin-tolerant (ST) patients attending a secondary-level outpatient lipid clinic. At the end of follow-up (mean 45 months), the evaluations were reassessed and bioelectrical impedance analysis (BIA)-assessed body composition, and muscle quality (handgrip/skeletal muscle mass) were further determined. Results: At baseline, BMI, cholesterol, and triglycerides in SI were higher than in ST patients. During follow-up, SI patients underwent a further increase in BMI and low-density lipoproteins (LDL)-cholesterol remained significantly higher than in ST patients. At the end of the follow-up, BIA-assessed fat mass percentage was higher in SI than in ST. Handgrip absolute values or standardized for skeletal muscle mass (muscle quality) were significantly lower in SI patients (p < 0.001), but this was confirmed only in their non-dominant arm (p < 0.01 for all arms). Circulating creatine kinase levels, which was higher in SI patients at baseline (p < 0.001), remained higher in those who never restarted statins after re-challenge (p = 0.029). Conclusions: Statin intolerance is clinically associated with lower muscle quality, particularly in less exercised arms. Full article

Statins are the cornerstone of lipid-lowering therapies effective for cardiovascular risk reduction. Although they are generally well tolerated, statin intolerance (SI) is frequent in clinical practice, and it is usually related to the onset of muscle symptoms, which are defined under the acronym SAMS (Statin-Associated Muscle Side Effects). These side effects are responsible for statin treatment discontinuation that results in increased cardiovascular risk. The National Lipid Association (NLA) has recently provided an updated definition of statin intolerance, and a distinction between complete and partial statin intolerance has been reported. The evaluation of symptom severity and the presence of muscle damage biomarker alterations make it essential to adopt a patient-centered approach aimed at obtaining a personalized therapeutic strategy. Firstly, it could be useful to administer a different statin, reduce the dosage or adopt an alternate dosage regimen. However, some patients are unable to tolerate any statin at every dosage, or despite taking statins at the maximum tolerated dose, they fail to achieve the recommended LDL-C target, and thus it is necessary to introduce a non-statin hypolipidemic treatment. Ezetimibe, proprotein-convertase subtilisin/kexin type 9 (PCSK9) inhibitors such as monoclonal antibodies (alirocumab and evolocumab) or RNA messenger silencing (inclisiran), bempedoic acid or nutraceuticals are non-statin lipid-lowering therapies that could be used as an alternative or in addition to statins to achieve an early and sustained LDL-C reduction in clinical practice. In this review, we evaluated SI management focusing on non-statin lipid lowering therapies and their implications in lipid lowering approaches in clinical practice. Full article

Introduction: In the United States, a significant amount of the population is affected by hyperlipidemia, which is associated with increased levels of serum low-density lipoprotein (LDL-C) and risk of cardiovascular disease. As of 2019, the guidelines set by the American College of Cardiology/American Heart Association advocate for the use of statins as the major contributor to lowering serum LDL-C. While proven to be effective, side effects, including muscle-related symptoms and new-onset diabetes mellitus, can make patients unable to tolerate statin therapy. Additionally, there is a subset of the population which does not approach a recommended LDL-C goal on statin treatment. Due to these findings, it was deemed necessary to review the literature of current statin-alternative lipid-lowering therapies. Methods: A systematic review of preclinical and clinical papers, and a current meta-analysis, was performed using PubMed and Google Scholar. Following the literature review, a meta-analysis was conducted using ProMeta 3. Results: Through systematic review and meta-analysis of the current literature, it is suggested that newer lipid-lowering therapies such as proprotein convertase subtilsin-kixen type 9 (PCSK9) inhibitors are a safe and effective statin alternative for the population with statin intolerance. PCSK9 inhibitors were shown to have no significant effect in causing myalgia in patients and showed no increase in adverse cardiovascular outcomes compared to a control of a current antilipemic medication regimen. Discussion: There are many statin-alternative therapies that should be investigated further as a potential replacement for patients with statin intolerance or as an addition for patients with statin resistance. Full article

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. Full article

Hyperlipidemia is a major risk factor for cardiovascular morbidity and mortality. Statins are the first-choice therapy for dyslipidemias and are considered the cornerstone of atherosclerotic cardiovascular disease (ASCVD) in both primary and secondary prevention. Despite the statin-therapy-mediated positive effects on cardiovascular events, patient compliance is often poor. Statin-associated muscle symptoms (SAMS) are the most common side effect associated with treatment discontinuation. SAMS, which range from mild-to-moderate muscle pain, weakness, or fatigue to potentially life-threatening rhabdomyolysis, are reported by 10% to 25% of patients receiving statin therapy. There are many risk factors associated with patient features and hypolipidemic agents that seem to increase the risk of developing SAMS. Due to the lack of a “gold standard”, the diagnostic test for SAMS is based on a clinical criteria score, which is independent of creatine kinase (CK) elevation. Mechanisms that underlie the pathogenesis of SAMS remain almost unclear, though a high number of risk factors may increase the probability of myotoxicity induced by statin therapy. Some of these, related to pharmacokinetic properties of statins and to concomitant therapies or patient characteristics, may affect statin bioavailability and increase vulnerability to high-dose statins. Full article

Statins are the cornerstone of lipid-lowering therapy. Although generally well tolerated, statin-associated muscle symptoms (SAMS) represent the main reason for treatment discontinuation. Mitochondrial dysfunction of complex I has been implicated in the pathophysiology of SAMS. The present study proposed to assess the concentration-dependent ex vivo effects of three statins on mitochondrial respiration in viable human platelets and to investigate whether a cell-permeable prodrug of succinate (complex II substrate) can compensate for statin-induced mitochondrial dysfunction. Mitochondrial respiration was assessed by high-resolution respirometry in human platelets, acutely exposed to statins in the presence/absence of the prodrug NV118. Statins concentration-dependently inhibited mitochondrial respiration in both intact and permeabilized cells. Further, statins caused an increase in non-ATP generating oxygen consumption (uncoupling), severely limiting the OXPHOS coupling efficiency, a measure of the ATP generating capacity. Cerivastatin (commercially withdrawn due to muscle toxicity) displayed a similar inhibitory capacity compared with the widely prescribed and tolerable atorvastatin, but did not elicit direct complex I inhibition. NV118 increased succinate-supported mitochondrial oxygen consumption in atorvastatin/cerivastatin-exposed platelets leading to normalization of coupled (ATP generating) respiration. The results acquired in isolated human platelets were validated in a limited set of experiments using atorvastatin in HepG2 cells, reinforcing the generalizability of the findings. Full article