Do statins cause myopathy?

If statins (HMG-CoA reductase inhibitors) cause myopathy, the risk is very low (strength of recommendation [SOR]: A). There is no direct evidence to answer this question. A pooled analysis of randomized controlled trials found similar myopathy rates in patients taking statins and placebo. However, a large cohort study revealed a very small but statistically significant increased risk of myopathy in patients taking statins (number needed to harm=10,000/year). Case reports suggest a myopathy risk for all statins, including fatal rhabdomyolysis. Risk of myopathy may increase with higher statin doses, certain comorbid states (eg, hypothyroidism, renal insufficiency [especially with diabetes], recent trauma, perioperative periods, advanced age, small body frame) and concurrent medications, including fibrates, cyclosporine, azole antifungals, and macrolide antibiotics (SOR: B). No studies have directly compared myopathy rates among statins, and there is no good evidence to suggest any differences. No controlled study has directly examined statin rechallenge in patients with previous myopathy; however, case reports and expert opinion support this practice (SOR: B)

Muscular Adverse Events Associated with Statins

Statins are an important group of lipid lowering medications that have helped to control cardiovascular mortality globally. Muscular side effects, mostly myalgia, is a known adverse event of statins. Intense physical activity, kidney or liver failure, hypothyroidism, inherited or metabolic myopathies, and some medications, are risk factors for statin-induced myalgia. Muscular adverse events are more often observed with higher doses or with the use of lipophilic statins. Much is not known about the precise mechanisms responsible for the statin related muscular adverse effects, a few hypothesis have been suggested. It is important to measure plasma creatine phosphokinase in subjects who encounter myalgia while being treated with statins. In this review we present some general safety information on muscular adverse events caused due to statins

Physicians' Experiences as Patients with Statin Side Effects: A Case Series.

Physicians are among those prescribed statins and therefore, subject to potential statin adverse effects (AEs). There is little information on the impact of statin AEs on physicians affected by them. We sought to assess the character and impact of statin AEs occurring in physicians and retired physicians, and to ascertain whether/how personal experience of AEs moderated physicians' attitude toward statin use. Seven active or retired physicians from the United States communicated with the Statin Effects Study group regarding their personal experience of statin AEs. AE characteristics, experience with (their own) physicians, and impact of AE was ascertained. We inquired whether or how their experience altered their own attitude toward statins or statin AEs. Patient A: Atorvastatin 40 then 80 mg was followed by cognitive problems, neuropathy, and glucose intolerance in a Radiologist in his 50s (Naranjo criteria: probable causality). Patient B: Atorvastatin 10 mg was followed in 2 months by muscle weakness and myalgia in an Internist in his 40s (probable causality). Patient C: Atorvastatin, ezetimibe/simvastatin, rosuvastatin at varying doses was followed shortly after by irritability, myalgia, and fatigue in a Cardiac Surgeon in his 40s (probable causality). Patient D: Simvastatin 20 then 40 mg was followed in 4 years by mitochondriopathy, myopathy, neuropathy, and exercise intolerance in an Emergency Medicine physician in his 50s (definite causality). Patient E: Simvastatin 20 mg and niacin 1000 mg was followed in one month by muscle weakness and myalgia in a Physical Medicine and Rehabilitation physician in his 50s (probable causality). Patient F: Lovastatin 20 mg then simvastatin 20 mg, atorvastatin 20 mg, rosuvastatin 5 mg, niacin 20 mg and ezetimbe 10 mg was followed by muscle weakness and myalgia in an Obstetrician/Gynecologist in his 70s (definite causality). Patient G: Ezetimibe/simvastatin and atorvastatin (dose unavailable) was followed shortly after by cognitive problems in a Radiologist in her 80s (probable causality). Thus AEs affected multiple quality-of-life relevant domains, often in combination, encompassing muscle (N = 5), fatigue (N = 2), peripheral neuropathy (N = 2), cognitive (N = 2), dysglycemia (N = 1) and behavioral manifestations (N = 1). In five, the AEs affected the physician professionally. Five physicians experienced dismissive attitudes in some of their own healthcare encounters. One noted that his experience helped not only his own attention to statin AEs, but that of other physicians in his community. Several stated that their experience altered their understanding of and/or attitude toward statin AEs, and/or their view of settings in which statin use is warranted. Statin AEs can have profound impact in high functioning professionals with implications to the individual, their professional life, and those whom they serve professionally

Efficacy and safety of atorvastatin and rosuvastatin in ischemic heart disease patients: A prospective study

Purpose: To compare the safety and efficacy of two commonly used statins namely; atorvastatin and rosuvastatin, and determine the efficiency of CoQ10 in the reversal of statin-induced myopathy. Methods: An investigational study design was adopted using randomized trials involving patients suffering from ischemic heart disease and receiving either atorvastatin or rosuvastatin. The study was conducted at Punjab Institute of Cardiology, Lahore, Pakistan during the period, November 2016 - February 2017. A total number of 95 male and female patients, between the ages of 40 and 80 years, were selected. Their blood samples were analyzed for lipid profile, total cholesterol, serum high-density lipoprotein-cholesterol (HDL-C), serum triglycerides, low-density lipoproteins-cholesterol (LDL-C) and total cholesterol/HDL-C ratio. Results: Gender and dose showed significant correlation with creatine phosphokinase (CPK) levels, (p = 0.001) and (p > 0.001), respectively. The patients using rosuvastatin 20 mg had a higher risk of developing myopathy than those treated with atorvastatin 40 mg (p = 0.023), while atorvastatin 20 mg patients were more prone to induce myopathy than 10 mg (p = 0.001) recipients. Atorvastatin 20 mg produced higher CPK levels than rosuvastatin 10 mg (p = 0.002). A substantial increase in CPK levels was found with rosuvastatin 20 mg and atorvastatin 20 mg usage (p > 0.001). It was observed that rosuvastatin 20 mg significantly increased the risk of myopathy compared to atorvastatin 10 mg (p > 0.001). However, rosuvastatin 20 mg/day considerably reduced the blood cholesterol as compared to atorvastatin 10mg/day (p = 0.001). CPK levels reduced significantly following treatment with CoQ10 (p = 0.022). Conclusion: Rosuvastatin users are more prone to the risk of myopathy, myalgic symptoms and rise in CPK levels than atorvastatin users, and these effects are dose related. CoQ10 is effective in lowering CPK levels and reversing myalgia

Statin-induced Myopathy

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide. HMGCoA reductase inhibitors or “statins” reduce low density lipoprotein cholesterol and reduce the risks of myocardial infarction, stroke and death in the presence of dyslipidaemia. In consequence, statins are prescribed to a large number of patients requiring primary or secondary prevention. A variety of side-effects may arise during the course of statin treatment which interfere with the quality of patients’ lives and reduce their compliance with therapy. Muscle symptoms constitute the most common of these side-effects and are the most frequent reason for discontinuing treatment. This review defi nes the muscle, tendon and joint disorders encountered by patients on statin treatment, their possible relationship to statin use, and the factors that facilitate the emergence of symptoms. The subtypes of statin myopathy are discussed and a general defi nition of statin myopathy is offered. Expert advice on managing statin myopathy is summarised

Phenotype standardization for statin-induced myotoxicity

Statins are widely used lipid-lowering drugs that are effective in reducing cardiovascular disease risk. Although they are generally well tolerated, they can cause muscle toxicity, which can lead to severe rhabdomyolysis. Research in this area has been hampered to some extent by the lack of standardized nomenclature and phenotypic definitions. We have used numerical and descriptive classifications and developed an algorithm to define statin-related myotoxicity phenotypes, including myalgia, myopathy, rhabdomyolysis, and necrotizing autoimmune myopathy.</p

Mitochondrial Oxidative Stress and Calcium-Dependent Permeability Transition are Key Players in the Mechanisms of Statins-Associated Side Effects

Statins are cholesterol-lowering medicines utilized worldwide and are associated with reduced risk of cardiovascular mortality and events. However, 0.5–10% of patients suffer from adverse effects especially on skeletal muscle. Recently, new onset of diabetes has been reported in subjects on statin therapy. Pro- and anti-oxidant effects of statins have been reported, thus fostering a debate. Previously reported data provide evidence that statins induce alterations in intracellular calcium homeostasis and mitochondrial dysfunctions that can be counteracted by antioxidants (e.g., CoQ10, creatine, and L-carnitine). Therefore, we have proposed that statin-induced inhibition of mitochondrial respiration leads to oxidative stress that opens a calcium-dependent permeability transition pore, an event that may lead to cell death. In addition, mitochondrial oxidative stress caused by statin treatment may be a signal for cellular antioxidant system responses such as catalase upregulation, possibly explaining the alleged statins’ antioxidant properties. Muscle mitochondrial dysfunction induced by statin treatment may be associated with the peripheral insulin resistance and may explain statins-induced new onset of diabetes. Together, the data presented in this review suggest that the statins’ detrimental effects can be prevented by co-administration of antioxidants

Imaging of Zebrafish In Vivo with Second-Harmonic Generation Reveals Shortened Sarcomeres Associated with Myopathy Induced by Statin

We employed second-harmonic generation (SHG) imaging and the zebrafish model to investigate the myopathy caused by statin in vivo with emphasis on the altered microstructures of the muscle sarcomere, the fundamental contractile element of muscles. This approach derives an advantage of SHG imaging to observe the striated skeletal muscle of living zebrafish based on signals produced mainly from the thick myosin filament of sarcomeres without employing exogenous labels, and eliminates concern about the distortion of muscle structures caused by sample preparation in conventional histological examination. The treatment with statin caused a significantly shortened sarcomere relative to an untreated control (1.73±0.09 µm vs 1.91±0.08 µm, P<0.05) while the morphological integrity of the muscle fibers remained largely intact. Mechanistic tests indicated that this microstructural disorder was associated with the biosynthetic pathway of cholesterol, or, specifically, with the impaired production of mevalonate by statins. This microstructural disorder exhibited a strong dependence on both the dosage and the duration of treatment, indicating a possibility to assess the severity of muscle injury according to the altered length of the sarcomeres. In contrast to a conventional assessment of muscle injury using clinical biomarkers in blood, such as creatine kinase that is released from only disrupted myocytes, the ability to determine microstructural modification of sarcomeres allows diagnosis of muscle injury before an onset of conventional clinical symptoms. In light of the increasing prevalence of the incidence of muscle injuries caused by new therapies, our work consolidates the combined use of the zebrafish and SHG imaging as an effective and sensitive means to evaluate the safety profile of new therapeutic targets in vivo