Adverse Effects Of Statin Therapy Research Articles

Statin-Induced Rhabdomyolysis: A Rare Case

ABSTRACT Statins are a group of lipid-lowering agents currently used as mainstay agents in the primary and secondary prevention of atherosclerotic cardiovascular heart disease. Rhabdomyolysis is one of the rare adverse effects of statin therapy, the incidence of which increases in the presence of risk factors. We report a rare case of statin-induced rhabdomyolysis presenting with acute kidney injury (AKI) requiring dialysis in the absence of risk factors. A 58-year-old diabetic and hypertensive female presented with pain and weakness of lower limbs, difficulty in walking, shortness of breath, and decreased urine output. She was receiving statin therapy for the past 1 week. Her blood investigations showed elevated creatine phosphokinase (CPK) and renal parameters. Electromyography and magnetic resonance imaging of thigh and calf muscles were suggestive of myositis. Statin was withdrawn and hemodialysis was done. The patient recovered gradually with no residual deficit. Statin-induced rhabdomyolysis is a rare but serious adverse effect requiring timely management. CPK levels along with thorough history and physical examination are useful to establish the diagnosis. Treatment is hydration and supportive therapy when diagnosed early. Hemodialysis is required in severe cases with AKI.

Interactions Between Statins, Exercise, and Health: A Clinical Update

Interactions Between Statins, Exercise, and Health: A Clinical Update

Adverse effects of statin therapy and their treatment

Statins are one of the most widely used drugs worldwide as first-line drugs for the treatment of hyperlipidemia and the prevention and treatment of cardiovascular diseases. Most of the side effects of statins are known to be mild, and mainly hepatotoxicity and various muscle symptoms are known. Recently, there have been studies on concerns about an increase in the incidence of diabetes after using statins, but it was found that the benefits sufficiently outweigh the risk of side effects. Therefore, the use of statins in the appropriate group should be actively performed, and it seems that the side effects can be prevented through close physical observation and appropriate examination.

Plethora of adverse drug reactions in geriatric population receiving statin therapy for dyslipidaemia.

Hyperlipidemia plays a major role in the pathogenesis of cardiovascular diseases (CVD). Statins are considered to be the most efficacious drugs in the management of hyperlipidemia and this class of drugs is most commonly prescribed for the treatment of hyperlipidemias. Although statin therapy has transformed the management of hyperlipidemia, it is associated with the skeletal muscle, neurological, and metabolic adverse effects. This study was conducted to evaluate the adverse effects of statin therapy in a geriatric population which may help in understanding whether these effects are dose-dependent. The study was conducted on 200 patients receiving statin therapy (atorvastatin and rosuvastatin) for hyperlipidemias. They were divided into four groups depending on the prescribed dose of atorvastatin and rosuvastatin. All study subjects were followed up for 6 months. The adverse effects reported by them during the statin therapy were documented and analyzed. All patients reported adverse effects after the initiation of statin therapy. Headache and muscle symptoms were among the most commonly reported adverse effects. There was no serious adverse effect (SAE). None of the adverse effects led to the discontinuation of the statin therapy. The results of this study suggest that all patients receiving statin therapy experience one or more adverse effects during the therapy. The adverse effects were not found to be severe in the geriatric age group.

To Prescribe or Deprescribe Statins, That Is the Question

To Prescribe or Deprescribe Statins, That Is the Question

Adverse effects of statin therapy: real evidence

Aim. To provide a current view on the tolerability and safety of statin therapy. Materials and methods. The data of 73 scientific sources from Russian and foreign literature published within 1996-2018 are considered. Results. It is generally accepted that statins are first-line therapeutic agents for hypercholesterolemia and combined hyperlipidemia. Today there in growing evidence that lowering of low-density lipoprotein cholesterol levels prevents atherosclerotic diseases and reduces a risk of cardiovascular and overall mortality. Main issues of current statin therapy include a use of inadequate dosage for atherosclerotic diseases prevention, low treatment compliance and drug intolerance. In recent years the issue of statin intolerance has become of great importance. Criteria were proposed for determining an inability to tolerate statins, some experts suggest replacing definition of “statin intolerance” with the term “statin-associated side-effects”. Most discussed adverse effects due to statins include muscle-related symptoms (myalgia/myopathy), hepatotoxicity (hepatic hyperenzymemia) new-onset diabetes, dementia and cognitive impairment. Mechanisms of development of these adverse effects are still unclear. Certain factors and conditions capable of triggering some adverse effects as well as absolute contraindications to statin therapy were established. Some factors and conditions capable of triggering some adverse effects as well as absolute contraindications to statin therapy were identified. Occurrence of statin-associated side-effects depends on statin dose, a patient's age, gender, comorbidity and concomitant therapy. Many adverse effects of statins are drug class effect. At the same time each of statins has specific features of its structure, metabolism, drug interactions and pharmacokinetics. Pitavastatin belongs to the last generation of statins and it has distinct pharmacological features and neutral diabetogenic effects, etc. Risk of adverse effects due to statins is often exaggerated while benefit from the use of statins for preventing atherosclerotic diseases outweighs potential risks. Real occurrence of some adverse effects due to statin therapy requires additional evidence. Conclusion. Overall, statins have a good tolerability profile and are approved for use in the vast majority of patients who required lipid-lowering therapy.

Efficacité et effets indésirables des statines: évidences et polémiques

ABSTRACT The introduction of statin therapy for the management of hypercholesterolemia was a breakthrough for the prevention of cardio vascular events in this condition and in patients at high cardio vascular risk, especially in people who have an evident cardio vascular disorder such as myocardial infarction or stroke. However recurrent criticisms raised questions on their efficacy and safety and led a substantial proportion of patients treated by this class of medication to stop their medication. The purpose of the report of the Academie nationale de medecine is to review evidences for efficacy, adverse effects of statin therapy and to analyze the causes of the « statin crisis » observed in several countries and in particular in France. Evidence for benefit in the prevention of cardio vascular diseases: The excess of cholesterol bound to low density lipoproteins is a well defined risk factor of cardio vascular diseases. The evidence derives from epidemiological studies, from the outcomes of familial hypercholesterolemia and from genome wide association studies. The mechanism of action of statins is linked to the inhibition of the cholesterol synthesis within the liver whereas other effects so called « pleiotropic » play a minimal role if any. High cholesterol plasma level is one out of other risk factors such as hypertension smoking or diabetes and international guidelines have released scores which allow to determine low, intermediate, high and very high risk subpopulations regarding the occurrence of major cardio vascular events. The magnitude of the reduction in LDL cholesterol is dependent on the type of statin, the two most powerful being atorvastatin and rosuvastatin and on dosage. The benefit conferred by statins has recently been evaluated in a large meta-analysis showing that treating 10 000 patients at high cardio vascular risk prevents 1440 major cardio vascular events when LDL cholesterol is lowered by 2mM/L. Statins are therefore a key treatment in patients at high or very high cardio vascular risk, particularly in secondary prevention. In patients at low risk statins also reduce the cardio vascular risk but the benefit is counterbalanced by the number of patients needed to treat, cost and side effects. Pharmaco-economic considerations are also important in this setting. Therefore there is consensus on the need to treat patients in secondary prevention or in primary prevention at high or very high cardio-vascular risk whereas the decision to treat people in low or intermediate risk categories should be individualized and take into consideration the benefit/risk ratio and cost. Muscular side effects are the most common adverse effects of statin therapy and are observed in 10-25 % of cases. They most often consist of muscular pain without evidence of muscular damage but in a minority of cases a myositis with necrosis of muscular tissue or a rhabdomyolisis with a risk of acute renal failure can occur. Dosage of Creatine Phospho kinase is recommended upon initiation of therapy and in case of muscular symptoms in order to detect the most severe forms of muscular side effects. Several risk factors have been identified including older age, female gender, alcohol consumption or treatment by colchicine. Liver toxicity with elevated liver enzymes has also been reported but it is uncommon. An increase in incident diabetes mellitus has also been reported particularly with rosuvastatin and atorvastatin but it seems to be a class effect and it is dose dependent. The underlying mechanism is unknown and the small increase in cardio vascular risk is offset by the cardio vascular benefit conferred by this therapy. Finally concerns on the potential risk of cognitive disorders have not been confirmed so far and some studies suggest on the contrary that statin therapy might slow down cognitive decline. Following several campaigns against statin therapy in France, it has been shown that the number of patients stopping their treatment had increased significantly including patients in secondary prevention, leading to a potential increase in major cardio vascular events. Several factors can explain why some patients are reluctant to start or continue their treatment: — A general concern about human activities and manufactured products including drugs versus « natural » products. — The loss of trust by the public in institutions and experts — The role of new media and social networks leading to the viral diffusion of biased or fake news. In conclusion the favorable benefit risk of statin therapy in patients with documented cardio vascular disease or at high risk is well documented and patient education on the benefit and adverse reaction of this class is key in order to restore trust it is in particular of paramount importance to inform patients of the risk induced by treatment interruption.

Statin associated myopathy in clinical practice. Results of DAMA study

Background and objectiveMuscle symptoms, with or without elevation of creatine kinase are one of the main adverse effects of statin therapy, a fact that sometimes limits their use. The aim of this study was to evaluate the clinical characteristics of patients treated with statins who have complained muscle symptoms and to identify possible predictive factors. Patients and methodsA cross-sectional one-visit, non-interventional, national multicenter study including patients of both sexes over 18 years of age referred for past or present muscle symptoms associated with statin therapy was conducted. 3845 patients were recruited from a one-day record from 2001 physicians. ResultsMyalgia was present in 78.2% of patients included in the study, myositis in 19.3%, and rhabdomyolysis in 2.5%. Patients reported muscle pain in 77.5% of statin-treated individuals, general weakness 42.7%, and cramps 28.1%. Kidney failure, intense physical exercise, alcohol consumption (>30g/d in men and 20g/d in women) and abdominal obesity were the clinical situations associated with statin myopathy. ConclusionsMyalgia followed by myositis are the most frequent statin-related side effects. It should be recommended control environmental factors such as intense exercise and alcohol intake as well as abdominal obesity and renal function of the patient treated with statins.

Miopatía asociada al uso de estatinas en la práctica clínica. Resultados del estudio DAMA

Background and objectiveMuscle symptoms, with or without elevation of creatin kinase are one of the main adverse effects of statin therapy, a fact that sometimes limits their use. The aim of this study was to evaluate the clinical characteristics of patients treated with statins who have complained muscle symptoms and to identify possible predictive factors. Patients and methodsA cross-sectional one-visit, non-interventional, national multicenter study including patients of both sexes over 18 years of age referred for past or present muscle symptoms associated with statin therapy was conducted. 3,845 patients were recruited from a one-day record from 2,001 physicians. ResultsMyalgia was present in 78.2% of patients included in the study, myositis in 19.3%, and rhabdomyolysis in 2.5%. Patients reported muscle pain in 77.5% of statin-treated individuals, general weakness 42.7%, and cramps 28.1%. Kidney failure, intense physical exercise, alcohol consumption (>30g/d in men and 20g/d in women) and abdominal obesity were the clinical situations associated with statin myopathy. ConclusionsMyalgia followed by myositis are the most frequent statin-related side effects. It should be recommended control environmental factors such as intense exercise and alcohol intake as well as abdominal obesity and renal function of the patient treated with statins.

Statin treatment is associated with insulin sensitivity decrease in type 1 diabetes mellitus: A prospective, observational 56-month follow-up study

Statins are effective in the primary and secondary prevention of cardiovascular events in individuals with and without diabetes. Emerging evidence, however, suggests that statins might reduce insulin sensitivity and secretion in healthy population and in type 2 diabetes. We aimed to investigate the effect of statin therapy introduction on insulin sensitivity in patients with type 1 diabetes mellitus (T1DM). This prospective observational 56-month long study included 832 randomly selected T1DM patients aged 25 to 61years. Uncontrolled dyslipidemia and clinician-perceived need for treatment, rather than randomization, were basis for individuals being started on either atorvastatin or simvastatin (10-40mg); N=345, 41.47%. Patients on statin treatment were compared with those unexposed to statin. Insulin sensitivity was assessed using equation derived from euglycemic-hyperinsulinemic clamp studies-estimated glucose disposal rate. Patients who started statin therapy (N=345, 59.42% atorvastatin and 40.58% simvastatin) experienced a greater decrease in insulin sensitivity (19.27% vs 12.82% P<.001) and metabolic control deterioration compared with statin-free group. The risk of decrease in insulin sensitivity attributable to statin use was 36.7% (hazard ratio 1.36; 95% confidence interval 1.31-1.43) after adjustment for age, gender, disease duration, smoking status, and the concomitant antihypertensive therapy. Although there is still a lack of a clear molecular explanation on the adverse effects of statin therapy on insulin sensitivity, we showed that it deteriorates insulin sensitivity in T1DM. The cardiovascular benefits of statin treatment might outweigh the risk of developing insulin resistance, but, the possible metabolic control worsening merits to be considered.

Dolichol: A Component of the Cellular Antioxidant Machinery.

Dolichol, an end product of the mevalonate pathway, has been proposed as a biomarker of aging, but its biological role, not to mention its catabolism, has not been fully understood. UV-B radiation was used to induce oxidative stress in isolated rat hepatocytes by the collagenase method. Effects on dolichol, phospholipid-bound polyunsaturated fatty acids (PL-PUFA) and known lipid soluble antioxidants [coenzyme Q (CoQ) and α-tocopherol] were studied. The increase in oxidative stress was detected by a probe sensitive to reactive oxygen species (ROS). Peroxidation of lipids was assessed by measuring the release of thiobarbituric acid reactive substances (TBARS). Dolichol, CoQ, and α-tocopherol were assessed by high-pressure liquid chromatography (HPLC), PL-PUFA by gas-liquid chromatography (GC). UV-B radiation caused an immediate increase in ROS as well as lipid peroxidation and a simultaneous decrease in the levels of dolichol and lipid soluble antioxidants. Decrease in dolichol paralleled changes in CoQ levels and was smaller to that in α-tocopherol. The addition of mevinolin, a competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoAR), magnified the loss of dolichol and was associated with an increase in TBARS production. Changes in PL-PUFA were minor. These findings highlight that oxidative stress has very early and similar effects on dolichol and lipid soluble antioxidants. Lower levels of dolichol are associated with enhanced peroxidation of lipids, which suggest that dolichol may have a protective role in the antioxidant machinery of cell membranes and perhaps be a key to understanding some adverse effects of statin therapy.

Statin intolerance - an attempt at a unified definition. Position paper from an International Lipid Expert Panel.

Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well tolerated and effectively prevent cardiovascular events. Most adverse effects associated with statin therapy are muscle-related. The recent statement of the European Atherosclerosis Society (EAS) has focused on statin associated muscle symptoms (SAMS), and avoided the use of the term ‘statin intolerance’. Although muscle syndromes are the most common adverse effects observed after statin therapy, excluding other side effects might underestimate the number of patients with statin intolerance, which might be observed in 10–15% of patients. In clinical practice, statin intolerance limits effective treatment of patients at risk of, or with, cardiovascular disease. Knowledge of the most common adverse effects of statin therapy that might cause statin intolerance and the clear definition of this phenomenon is crucial to effectively treat patients with lipid disorders. Therefore, the aim of this position paper was to suggest a unified definition of statin intolerance, and to complement the recent EAS statement on SAMS, where the pathophysiology, diagnosis and the management were comprehensively presented.

Viewpoint: Personalizing Statin Therapy

Cardiovascular disease (CVD), associated with vascular atherosclerosis, is the major cause of death in Western societies. Current risk estimation tools, such as Framingham Risk Score (FRS), based on evaluation of multiple standard risk factors, are limited in assessment of individual risk. The majority (about 70%) of the general population is classified as low FRS where the individual risk for CVD is often underestimated but, on the other hand, cholesterol lowering with statin is often excessively administered. Adverse effects of statin therapy, such as muscle pain, affect a large proportion of the treated patients and have a significant influence on their quality of life.Coronary artery calcification (CAC), as assessed by computed tomography, carotid artery intima-media thickness (CIMT), and especially presence of plaques as assessed by B-mode ultrasound are directly correlated with increased risk for cardiovascular events and provide accurate and relevant information for individual risk assessment. Absence of vascular pathology as assessed by these imaging methods has a very high negative predictive value and therefore could be used as a method to reduce significantly the number of subjects who, in our opinion, would not benefit from statins and only suffer from their side-effects.In summary, we suggest that in very-low-risk subjects, with the exception of subjects with low FRS with a family history of coronary artery disease (CAD) at young age, if vascular imaging shows no CAC or normal CIMT without plaques, statin treatment need not be administered.

Do the Frequencies of Adverse Events Increase, Decrease, or Stay the Same with Long-Term Use of Statins?

Statins are widely used for their cholesterol-lowering properties and proven reduction of cardiovascular disease risk. Many patients take statins as long-term treatment for a variety of conditions without a clear-cut understanding of how treatment duration affects the frequency of adverse effects. We aimed to evaluate whether the frequencies of documented adverse events increase, decrease, or remain unchanged with long-term statin use. We reviewed the established literature to define the currently known adverse effects of statin therapy, including myopathy, central nervous system effects, and the appearance of diabetes, and the frequency of these events with long-term medication use. The frequency of adverse effects associated with long-term statin therapy appears to be low. Many patients who develop side effects from statin therapy do so relatively soon after initiation of therapy, so the frequency of side effects from statin therapy when expressed as a percentage of current users decreases over time. Nevertheless, patients may develop side effects such as muscle pain and weakness years after starting statin therapy; however, the absolute number of patients affected by statin myopathy increases with treatment duration. Also, clinical trials of statin therapy rarely exceed 5years, so it is impossible to determine with certainty the frequency of long-term side effects with these drugs.

HMG-CoA Reductase Inhibitors and Coenzyme Q10

The most concerning adverse reaction with HMG-CoA reductase inhibitors (statins) is myotoxicity. Statins inhibit the production of mevalonate, a precursor of both cholesterol and coenzyme Q10, a compound believed to be crucial for mitochondrial function and the provision of energy for cellular processes. There is speculation that a reduction in coenzyme Q10 concentrations may promote the myopathies that have been associated with statin treatment as a result of mitochondrial damage. Although studies have repeatedly demonstrated a reduction in circulating coenzyme Q10 concentrations with statin therapy, it is unclear as to whether tissue levels of coenzyme Q10 are significantly affected. Coenzyme Q10 supplementation has been shown to reverse statin-induced decreases in circulating coenzyme Q10 concentrations, although the effect of supplementation on tissue coenzyme Q10 concentrations and any resulting clinical benefit has not been adequately assessed. Although there is not much of a safety concern with coenzyme Q10 supplementation, there is also not enough evidence to support its routine use for preventing the adverse effects of statin therapy, and it is therefore not recommended for this purpose at this time.