Side Effects Of Statin Therapy Research Articles

Differential diagnosis of unconjugated hyperbilirubinemiadetected after coronary artery stenting

Introduction. An increase in bilirubin and liver enzyme activity may be one of the side effects of statin therapy, often occurring in patients after AMI and coronary artery stenting, or in high and very high risk individuals on high and moderate intensity statin therapy. The frequency of occurrence of increased transaminases and bilirubin is according to different authors. Therefore, in terms of differential diagnosis, the cardiologist should consider Gilbert’s syndrome as a possible cause of hyperbilirubinemia. Description of the clinical case. The article considers a clinical case of differential diagnosis of non-conjugated hyperbilirubinemia detected in a patient after coronary artery stenting. The level of hemoglobin, erythrocytes, reticulocytes did not differ from normal values and did not change over time. This made it possible to exclude the hemolytic genesis of hyperbilirubinemia. Genetic testing was used to establish the homozygous form of Gilbert’s syndrome. However, the presence of fibrotic changes in the liver, an increase in not only unconjugated, but also conjugated bilirubin, hypertriglyceridemia, dyslipidemia, and stenosing atherosclerosis of the coronary arteries did not allow us to state that the patient had only Gilbert’s syndrome. Discussion. According to recent studies, this disease is characterized by a benign course and reduces the risk of developing cardiovascular diseases due to the antioxidant effect of bilirubin. In addition to Gilbert’s syndrome, the patient was diagnosed with an erased form of non-alcoholic fatty liver disease associated with metabolic syndrome. Conclusion. The disease was caused by insulin resistance, a high-calorie diet, excess consumption of saturated fats, refined carbohydrates, and a sedentary lifestyle. The drugs of choice in this case are statins, ezetemibe, and ursodeoxycholic acid. Their appointment allows not only to reduce cardiovascular risk, but also to slow down the further progression of liver fibrosis.

The Problem of Drug Interactions Between Rosuvastatin and Ticagrelor in the Aspect of the Risk of Rhabdomyolysis: Discussion of the Problem and Description of the Clinical Case

Background. Combination therapy with two antiplatelet agents (ticagrelor or clopidogrel plus acetylsalicylic acid) and a high dose statin is recommended in accordance with clinical guidelines for patients undergoing acute coronary syndrome and coronary intervention. Combined therapeutic regimens have drug-drug interaction potential. Rhabdomyolysis is a known side effect of statin therapy, and there is evidence that co-therapy with ticagrelor increases the risk of this complication.Case description. A 72-year-old female patient was hospitalized with typical signs of rhabdomyolysis: muscle pain, oliguria, weakness, significant increases in creatine kinase (CK), myoglobin and creatinine. One month before that, she was urgently hospitalized with acute recurrent ST-elevation myocardial infarction and underwent endovascular intervention on a critical stenosis of the left anterior descending artery with stent implantation. After that, rosuvastatin 40 mg per day and ticagrelor 90mg 2 times a day were added to her therapy. During the current hospitalization, rosuvastatin, ACE inhibitors and spirolactone were canceled, infusion therapy was carried out, which led to a rapid regression of symptoms, restoration of adequate diuresis, and normalization of CK, myoglobin and creatinine levels. Conclusions. The combined use of ticagrelor with rosuvastatin (especially at a high dose) increases the risk of rhabdomyolysis in elderly patients. Patients taking ticagrelor may require changes in statin therapy, dose adjustments, and possible drug changes to avoid pharmacological interactions and an increased risk of side effects.

Clinical Features of Familial Hypercholesterolemia in Children and Adults in EAS-FHSC Regional Center for Rare Diseases in Poland.

Background: Familial hypercholesterolemia (FH) is a genetic autosomal co-dominant metabolic disorder leading to elevated circulating concentrations of low-density lipoprotein cholesterol (LDL-C). Early development of atherosclerotic cardiovascular disease (ASCVD) is common in affected patients. We aimed to evaluate the characteristics and differences in the diagnosis and therapy of FH children and adults. Methods: All consecutive patients who were diagnosed with FH, both phenotypically and with genetic tests, were included in this analysis. All patients are a part of the European Atherosclerosis Society FH-Study Collaboration (FHSC) regional center for rare diseases at the Polish Mother’s Memorial Hospital Research Institute (PMMHRI) in Lodz, Poland. Results: Of 103 patients with FH, there were 16 children (15.5%) at mean age of 9 ± 3 years and 87 adults aged 41 ± 16; 59% were female. Children presented higher mean levels of total cholesterol, LDL-C, and high-density lipoprotein cholesterol (HDL-C) measured at the baseline visit (TC 313 vs. 259 mg/dL (8.0 vs. 6.6 mmol/L), p = 0.04; LDL 247 vs. 192 mg/dL (6.3 vs. 4.9 mmol/L), p = 0.02, HDL 53 vs. 48 mg/dL (1.3 vs. 1.2 mmol/L), p = 0.009). Overall, 70% of adult patients and 56% of children were prescribed statins (rosuvastatin or atorvastatin) on admission. Combination therapy (dual or triple) was administered for 24% of adult patients. Furthermore, 13.6% of adult patients and 19% of children reported side effects of statin therapy; most of them complained of muscle pain. Only 50% of adult patients on combination therapy achieved their treatment goals. None of children achieved the treatment goal. Conclusions: Despite a younger age of FH diagnosis, children presented with higher mean levels of LDL-C than adults. There are still urgent unmet needs concerning effective lipid-lowering therapy in FH patients, especially the need for greater use of combination therapy, which may allow LDL-C targets to be met in most of the patients.

The Association between Apolipoprotein E Polymorphism and Response to Statins in Group of Hyperlipidemic Patients.

APOE has an important role in lipids metabolism, and in the variability in low density lipoprotein (LDL) response to statins treatment between individuals. In this study, we aim to investigate the association between APOE polymorphism and response to statins in Jordanian hyperlipidemic patients at the diabetic clinic of Jordan University Hospital. One hundred and fifty two Jordanian Hyperlipidemic patients (52 males and 100 females) aged between 35-75 years were enrolled in this study. This study was approved by the Institutional Review Board (IRB) of Jordan University Hospital. The genotypes of the patients were identified by polymerase chain reaction followed by restriction fragment length polymorphism assay method (PCRRFLP). The study showed that there is an association between APOE polymorphism and response to statin therapy. Patients who were APOE ε4 carriers had lower response to statins compared to ε3 and ε2 carriers (p=0.002). In addition, we found that there was no significant association between APOE polymorphism and LDL baseline (p=0.214). No significant differences were found in APOE genotypes distribution between males and females (p=0.06). No significant association was found between age and APOE genotypes (p=0.347). A genotype screening test for dyslipidemic Jordanian patients is recommended to choose the appropriate treatment decisions, dosage, and to recognize the potential side effects of statin therapy.

Treatment with Statins in Elderly Patients.

Elderly patients are a special category of patients, due to the physiological changes induced by age, the great number of comorbidities and drug treatment and last, but not least, to the cognitive dysfunction frequently encountered in this population. Cardiovascular disease is the most important cause of morbidity and mortality in elderly individuals worldwide. The rate of cardiovascular events increases after 65 years in men and after 75 years in women. Myocardial infarction and stroke are the leading disorders caused by atherosclerosis, that lead to death or functional incapacity. Elderly people have a greater risk to develop atherosclerotic cardiovascular disease. The incidence and prevalence of atherosclerosis increase with age and the number of cardiovascular events is higher in elderly patients. The most efficient treatment against atherosclerosis is the treatment with statins, that has been shown to decrease the risk both of stroke and coronary artery disease in all age groups. The advantages of the treatment become evident after at least one year of treatment. Primary prevention is the most important way of preventing cardiovascular disease in elderly individuals, by promoting a healthy lifestyle and reducing the risk factors. Secondary prevention after a stroke or myocardial infarction includes mandatory a statin, to diminish the risk of a recurrent cardiovascular event. The possible side effects of statin therapy are diabetes mellitus, myopathy, and rhabdomyolysis, hepatotoxicity. The side effects of the treatment are more likely to occur in elderly patients, due to their multiple associated comorbidities and drugs that may interact with statins. In elderly people, the benefits and disadvantages of the treatment with statins should be put in balance, especially in those receiving high doses of statins.

The STatin Adverse Treatment Experience Survey: Experience of patients reporting side effects of statin therapy

It is important to understand patients' experiences of statin-associated adverse effects to potentially identify those at risk for stopping treatment. The goal of the STatin Adverse Treatment Experience survey was to describe patients' experiences after reporting ≥1 recent statin-associated adverse event and identify opportunities to improve adherence and outcomes. The survey was developed in 3 stages: qualitative item development, pilot evaluation of initial item performance, and quantitative evaluation using a large commercial sample. Respondents with self-reported high cholesterol who had taken a statin in the past 2years and experienced ≥1 statin-associated symptom in the past 6months were included (N=1500). Mean age was 58years, 40.3% were men, and 43.2% had tried ≥2 statins. Many had clinical comorbidities associated with increased risk for cardiovascular disease (atherosclerotic cardiovascular disease, 22.5%; diabetes, 25.8%; hypertension, 56.0%). The most important patient-reported reasons for continuing current statin therapy (n=1168; 77.9%) were avoiding a heart attack or stroke, lowering cholesterol, and doctor recommendation. Being bothered by and not being able to tolerate side effects were the main reasons respondents discontinued statins (n=332; 22.1%). Respondents who discontinued statins reported significantly higher mean Symptom Severity (10.6 vs 8.7, P<.001) and Impact Severity scores (11.8 vs 9.8, P<.001) compared with those who continued. The STatin Adverse Treatment Experience survey highlights the importance of patients' adverse experiences with statins and how symptom and impact scores affect decisions to continue or discontinue therapy. These data provide a foundation to increase providers' awareness of statin tolerability from the patient's perspective and encourage benefit-risk discussions.

Vitamin D Serum Levels in Patients with Statin-Induced Musculoskeletal Pain.

Introduction Statin-associated muscle symptoms are common side effects of statin therapy. These symptoms include myopathy, myalgia, and rhabdomyolysis. Vitamin D has been associated with musculoskeletal health; thus, its deficiency may produce detrimental effects in this tissue. Indeed, one symptom of vitamin D deficiency is myalgia, and the normalization of low vitamin D levels can relieve it. Patients and Methods This cross-sectional study examined 1210 statin-treated patients to assess vitamin D status. These patients were divided into two groups: 287 with statin-associated muscle symptoms (SAMS) and 923 control patients without SAMS. Results We have found a significant association between deficient and insufficient vitamin D status and statin-associated muscle symptoms (SAMS). Vitamin D deficiency (<30 nmol/L) presents 77% (95% C.I. 71.6% to 81.7%) sensitivity and 63.4% (95% C.I. 60.2% to 66.5%) specificity in diagnosing SAMS. Odds ratio analysis showed that this association is moderate-strong both for deficient and for insufficient status. Conclusion We found a correlation between vitamin D deficiency and SAMS. Therefore, vitamin D levels may be useful for the diagnosis and management of SAMS.

Statin-related myotoxicity

Statin therapy has a very important role in decreasing cardiovascular risk, and treatment non-compliance may therefore be a concern in high cardiovascular risk patients. Myotoxicity is a frequent side effect of statin therapy and one of the main causes of statin discontinuation, which limits effective treatment of patients at risk of or with cardiovascular disease. Because of the high proportion of patients on statin treatment and the frequency of statin-related myotoxicity, this is a subject of concern in clinical practice. However, statin-related myotoxicity is probably underestimated because there is not a gold standard definition, and its diagnosis is challenging. Moreover, information about pathophysiology and optimal therapeutic options is scarce. Therefore, this paper reviews the knowledge about the definition, pathophysiology and predisposing conditions, diagnosis and management of statin-related myotoxicity, and provides a practical scheme for its management in clinical practice.

Lowering cholesterol in chronic kidney disease: is it safe and effective?

The value of cholesterol lowering in preventing cardiovascular disease has now been established in patients with chronic kidney disease (CKD), who are intrinsically at high cardiovascular risk. While data from completed studies has clearly demonstrated substantive benefit of statins in early CKD, the effects in end-stage CKD remain controversial. Recent studies have also suggested that the effects of different statins on the kidney may be heterogeneous, and the safety of high-dose statins in this population remains uncertain. Communications from regulators such as the US Food and Drug Administration concerning potential side effects of statin therapy (particularly memory loss and the risk of diabetes) have created debate in the medical literature and unrest in the public mind about the value of long-term statin therapy for vulnerable patient populations. The evaluation of risks and benefits for this class of agents is critically dependent on baseline risk. This article will review current evidence for the benefits and risks of statin therapy for kidney and cardiovascular disease progression in the CKD population.

Lovastatin-Mediated Changes in Human Tendon Cells.

Statins are among the most widely prescribed drugs worldwide. Numerous studies have shown their beneficial effects in prevention of cardiovascular disease through cholesterol‐lowering and anti‐atherosclerotic properties. Although some statin patients may experience muscle‐related symptoms, severe side effects of statin therapy are rare, primarily due to extensive first‐pass metabolism in the liver. Skeletal muscles appear to be the main site of side effects; however, recently some statin‐related adverse effects have been described in tendon. The mechanism behind these side effects remains unknown. This is the first study that explores tendon‐specific effects of statins in human primary tenocytes. The cells were cultured with different concentrations of lovastatin for up to 1 week. No changes in cell viability or morphology were observed in tenocytes incubated with therapeutic doses. Short‐term exposure to lovastatin concentrations outside the therapeutic range had no effect on tenocyte viability; however, cell migration was reduced. Simvastatin and atorvastatin, two other drug family members, also reduced the migratory properties of the cells. Prolonged exposure to high concentrations of lovastatin induced changes in cytoskeleton leading to cell rounding and decreased levels of mRNA for matrix proteins, but increased BMP‐2 expression. Gap junctional communication was impaired but due to cell shape change and separation rather than direct gap junction inhibition. These effects were accompanied by inhibition of prenylation of Rap1a small GTPase. Collectively, we showed that statins in a dose‐dependent manner decrease migration of human tendon cells, alter their expression profile and impair the functional network, but do not inhibit gap junction function. J. Cell. Physiol. 230: 2543–2551, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

An insight into statin use and its association with muscular side effects in clinical practice.

Muscular complaints are known side-effects of statin therapy, ranging from myalgia to clinically important myositis and rhabdomyolysis. We investigated the statin use and association with the presence and characteristics of muscular complaints. We conducted a prospective observational study in internal medicine departments. Patients with statin therapy before hospitalization were interviewed for muscular complaints. When muscular complaints were reported, information on type and severity of muscular symptoms, location and time to onset was collected. We identified 85 patients with statin treatment at hospital admission out of 521 included. Nine (10.59%) patients reported muscular complaints associated with statin therapy. A cluster of symptoms (cramps, stiffness, decreased muscle power) was reported, affecting both upper and lower limbs. The severity of pain was in most of the cases moderate or severe. All patients reported that pain was intermittent. Five reported that pain was generalized. Symptoms appeared in the first month of treatment or three months after the drug initiation. Creatine kinase was raised in one patient. In two cases drug interactions were probably responsible for muscular complaints. In the studied set of patients muscular symptoms were a rather frequent effect of statin therapy. As this side-effect could be troublesome for patients and could lead to more severe outcomes, their timely detection and management is important.

Homoeopathy in the management of Dyslipidemia: A short review

The importance of high serum total cholesterol and high level of low-density lipoprotein cholesterol, as a risk factor for coronary artery diseases is well established. Statin is the first-line of treatment for dyslipidemia and there are known side effects of statin therapy. This study reviews the existing information available in Homoeopathy (research and traditional knowledge) for managing dyslipidemia. No rigid inclusion has been kept due to scarcity of evidence-based literature. Preclinical and clinical studies (case records to controlled trials) are included. A comprehensive search from major biomedical databases including National Medical Library (PubMed), AYUSH PORTAL, EMBASE, and the Cochrane Library was conducted using the search term “dyslipidemia,” “atherosclerosis,” “arteriosclerosis,” “atheroma” along with “Homoeopathy.” In addition, efforts were made to search authoritative texts of authors, such homoeopathic Materia Medica, repertory, etc. Relevant research was categorized by study type and appraised according to study type and design. Four preclinical, three observational studies, and two case records were identified. From literary search, medicines commonly used in Materia Medica and drugs of Indian origin were noted. There are positive leads in managing patients suffering from dyslipidemia. However, more well-designed studies are warranted to generate effectiveness/efficacy of Homoeopathy.

MYOPATHY AS A SIDE EFFECT OF STATIN THERAPY: MECHANISMS OF DEVELOPMENT AND PROSPECTS FOR TREATMENT

Statins are lipid-lowering drugs with proven efficacy that reduce cardiovascular risk and are well tolerated by most patients. Myopathy as a side effect of statin therapy is one of the most common reasons for their withdrawal. Its severity can range from asymptomatic increase of serum CPK to life-threatening rhabdomyolysis. Therefore it is necessary to remember about the possibility of its occurrence. The exact molecular mechanisms of muscle damage by statins are still unknown. Various hypotheses are suggested in this respect: fatty acid oxidation disorders, mitochondrial dysfunction, increased protein degradation in myocytes due to changes in atrogin-1 and ubiquitin activity, activation of autoimmune processes, intracellular depletion of essential metabolites, destabilization of cell membranes, impaired expression of genes involved in apoptosis and protein degradation. The theory that the reduction of intramuscular CoQ10 level is the cause of myopathy prevails. Additional intake of CoQ10 seems promising, but is not evidence-based.

Lipidsenkende Therapie bei geriatrischen Patienten

Cardiovascular disease is also the most frequent cause of mortality in the elderly population. Invasive diagnostic and therapeutic interventions are performed at an increasing rate in older patients in order to maintain functional capacities and, thus, an adequate quality of life. Thus, strategies to prevent cardiovascular events (e.g., lipid lowering therapy) are also of great importance in elderly. With respect to the side effects of statin therapy, the risk of drug interaction has to be considered, as well as myopathy. Discrepant study results exist about the influence of statins on cognitive function. Retrospective analyses indicate that statin therapy might be related to an increased risk for type.2 diabetes in certain risk groups. The indication for statin therapy should, therefore, consider the risk profile and especially the individual situation of the older patient.

Statin-Associated Polymyositis Following Omeprazole Treatment

Statins are an extensively used class of drugs, and myopathy is an uncommon, but well-described side effect of statin therapy. Inflammatory myopathies, including polymyositis, dermatomyositis, and necrotizing autoimmune myopathy, are even more rare, but debilitating, side effects of statin therapy that are characterized by the persistence of symptoms even after discontinuation of the drug. It is important to differentiate statin-associated inflammatory myopathies from other self-limited myopathies, as the disease often requires multiple immunosuppressive therapies. Drug interactions increase the risk of statin-associated toxic myopathy, but no risk factors for statin-associated inflammatory myopathies have been established. Here we describe the case of a man, age 59 years, who had been treated with a combination of atorvastatin and gemfibrozil for approximately 5 years and developed polymyositis after treatment with omeprazole for 7 months. Symptoms did not resolve after discontinuation of the atorvastatin, gemfibrozil, and omeprazole. The patient was treated with prednisone and methotrexate followed by intravenous immunoglobulin, which resulted in normalization of creatinine kinase levels and resolution of symptoms after 14 weeks. It is unclear if polymyositis was triggered by interaction of the statin with omeprazole and/or gemfibrozil, or if it developed secondary to long-term use of atorvastatin only.

Simvastatin Effects on Skeletal Muscle: Relation to Decreased Mitochondrial Function and Glucose Intolerance

Glucose tolerance and skeletal muscle coenzyme Q(10) (Q(10)) content, mitochondrial density, and mitochondrial oxidative phosphorylation (OXPHOS) capacity were measured in simvastatin-treated patients (n = 10) and in well-matched control subjects (n = 9). A prevalent side effect of statin therapy is muscle pain, and yet the basic mechanism behind it remains unknown. We hypothesize that a statin-induced reduction in muscle Q(10) may attenuate mitochondrial OXPHOS capacity, which may be an underlying mechanism. Plasma glucose and insulin concentrations were measured during an oral glucose tolerance test. Mitochondrial OXPHOS capacity was measured in permeabilized muscle fibers by high-resolution respirometry in a cross-sectional design. Mitochondrial content (estimated by citrate synthase [CS] activity, cardiolipin content, and voltage-dependent anion channel [VDAC] content) as well as Q(10) content was determined. Simvastatin-treated patients had an impaired glucose tolerance and displayed a decreased insulin sensitivity index. Regarding mitochondrial studies, Q(10) content was reduced (p = 0.05), whereas mitochondrial content was similar between the groups. OXPHOS capacity was comparable between groups when complex I- and complex II-linked substrates were used alone, but when complex I + II-linked substrates were used (eliciting convergent electron input into the Q intersection [maximal ex vivo OXPHOS capacity]), a decreased (p < 0.01) capacity was observed in the patients compared with the control subjects. These simvastatin-treated patients were glucose intolerant. A decreased Q(10) content was accompanied by a decreased maximal OXPHOS capacity in the simvastatin-treated patients. It is plausible that this finding partly explains the muscle pain and exercise intolerance that many patients experience with their statin treatment.

Survey of Statin Use in a Nursing Home Population

Background: The clinical benefits in regards to various indications of statin therapy for secondary prevention have been widespread. However, the effects and benefits of such therapies in the elderly nursing home population are not well studied. Current data supporting use of statins includes elders with mean age of 66 years; 60-71 years; 75 years, and a maximum age 82 years. Objective/Aim: To review the use of statins in a nursing home population by evaluating patient factors such as: age, diagnosis, type and dosing of statin used, monitoring parameters, renal function and drug interactions. (Observed differences in prescribing patterns were also reviewed). Quality Improvement Methods: The survey used involved quantitative and qualitative retrospective chart review to obtain: Patient name, age, gender, and location. Other data collected included the type of statin therapy used, dose, any renal adjustment, and documentation of muscle soreness. Any pertinent labs were checked for appropriate monitoring of lipid panel, liver function, creatinine kinase level and kidney function. The concomitant use of medications, which are considered high risk when used with statins, was also assessed. Results: Out of the 183 nursing home residents reviewed, 32 were receiving regular statin therapy. The major indication for statin use was hyperlipidemia (68.8%), followed by coronary artery disease (46.9%) diabetic coronary artery disease (12.5%), and cerebral vascular disease (18.8%). Regular lipid monitoring was performed in 62.5 percent of the reviewed residents, while the remaining 37.5 percent were not adequately monitored, there was not even a single lipid panel included in their chart. LFTs were performed in majority of the patients (84.3%). Most evident was the lack of creatinine kinase level monitoring, with only one resident out of the 32 reviewed having creatinine kinase level checked. Also, there was no documentation to support that the most common side effect of statin therapy, muscle pain, was even assessed. Conclusions: Monitoring efficacy of drug exposure is a basic principle of best practices in geriatric pharmacotherapy, but is an ongoing concern in the nursing home population. Analysis includes statin use in palliative cohorts, inappropriate dosing, and discussion of appropriateness of statin use in the nursing home population. Author Disclosures: All authors have stated there are no disclosures to be made that are pertinent to this abstract.

High Degree of Adherence to Statin Therapy Among the Elderly Despite High Frequency of Side Effects

The aims of the present study were to investigate adherence and side effects of statin therapy in elderly patients (≥75 years) after primary statin prescription, to identify possible differences related to whether statin treatment was initiated in primary care or in hospital, and to investigate whether there was any correlation between side effects of statin therapy and statin dose or renal impairment. In two primary health care populations, all patients ≥75 years of age recently initiated on statin therapy were identified through the patient data records (n = 90) and asked to complete a questionnaire. Of 68 subjects responding to the questionnaire, 87% reported adherence to the statin therapy and 29% reported side effects. No statistically significant difference was seen for adherence or frequency of side effects depending on whether therapy was initiated in primary care or in hospital. In conclusion, elderly patients appear to exhibit a high degree of adherence to statin treatment despite a high incidence of side effects.

Squalene Synthase Inhibitor Lapaquistat Acetate

Elevated serum cholesterol level is an important risk factor for cardiovascular disease,1 and cholesterol lowering by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins has been shown to reduce cardiovascular events.2 The reduction in cardiovascular risks with statin therapy, whether for primary or secondary prevention, correlates almost linearly with the reduction in serum cholesterol levels.3 Indeed, for every 30 mg/dL decrease in low-density lipoprotein-cholesterol (LDL-C), there is a concomitant 30% decrease in cardiovascular events.2 For patients presenting with acute coronary syndrome,4 or in patients with stable coronary artery disease,5 intensive lipid-lowering therapy provides even greater clinical benefits, implying that the lower the LDL-C, the better the outcome is, especially for high-risk patients. Because most of the US adult population with coronary heart disease has serum LDL-C levels between 135 and 145 mg/dL,6 to achieve an Adult Treatment Panel III/National Cholesterol Education Panel guideline for LDL-C target goal of <100 mg/dL with an optional goal of <70 mg/dL, most high-risk patients with coronary heart disease will likely require at least a 40% to 50% reduction in LDL-C.2 Article see p 1974 Depending on the dose used, most statins can reduce serum cholesterol by 30% to 58%.7 This is compared with bile acid sequestrants or intestinal cholesterol absorption inhibitors, which tend to lower serum cholesterol by only 15% to 18%. Thus, it is not surprising that statins have emerged as the principal cholesterol-lowering therapy for patients at risk for cardiovascular disease. However, most statins, with the exception of the more potent statins, such as atorvastatin and rosuvastatin, will require near-maximum dosages to achieve a 40% to 50% LDL-C reduction. This is because the majority of statins' LDL-C–lowering efficacy occurs at the starting dose with only a modest 4% to 6% further LDL-C reduction with …

Treating statin-intolerant patients

Statins are effective in reducing cardiovascular events and are safe for almost all patients. Nevertheless, intolerance to statins is frequently faced in clinical practice. This is mostly due to muscular symptoms (myalgia with or without increase of plasma creatinine kinase) and/or elevation of hepatic aminotransferases, which overall constitutes approximately two-thirds of reported adverse events during statin therapy. These side effects raise concerns in patients as well as in doctors and are likely to reduce patients’ adherence and, as a consequence, the cardiovascular benefit. Therefore, it is mandatory that clinicians improve their knowledge on the clinical aspects of muscular and hepatic side effects of statin therapy as well as their ability to manage patients with statin intolerance. Besides briefly examining the clinical aspects and the mechanisms that are proposed to be responsible for the most common statin-associated side effects, the main purpose of this article is to review the available approaches to manage statin-intolerant patients. The first step is to determine whether the adverse events are indeed related to statin therapy. If so, lowering the dosage or changing statin, alternate dosing options, or the use of nonstatin compounds may be practical strategies. The cholesterol-lowering potency as well as the usefulness of these different approaches in treating statin-intolerant patients will be examined based on currently available data. However, the cardiovascular benefit of these strategies has not been well established, so their use has to be guided by a careful clinical assessment of each patient.