Muscle problems and other adverse symptoms associated with statin use are frequent reasons for non-adherence and discontinuation of statin therapy, which results in inadequate control of hyperlipidemia and increased cardiovascular risk. However, most patients who experience adverse symptoms during statin use are able to tolerate at least some degree of statin therapy. Given the profound cardiovascular benefits derived from statins, an adequate practical approach to statin intolerance is, therefore, of great clinical importance. Statin intolerance can be defined as the occurrence of myalgia or other adverse symptoms that are attributed to statin therapy and that lead to its discontinuation. In reality, these symptoms are actually unrelated to statin use in many patients, especially in those with atypical presentations following long periods of treatment. Thus, the first step in approaching patients with adverse symptoms during the course of statin therapy is identification of those patients for whom true statin intolerance is unlikely, since most of these patients would probably be capable of tolerating adequate statin therapy. In patients with statin intolerance, an altered dosing regimen of very low doses of statins should be attempted and, if tolerated, should gradually be increased to achieve the highest tolerable doses. In addition, other lipid-lowering drugs may be needed, either in combination with statins, or alone, if statins are not tolerated at all. Stringent control of other risk factors can aid in reducing cardiovascular risk if attaining lipid treatment goals proves difficult.

• Keywords
• Low-dose statin therapy, Muscle side effects, Myalgia, Statin, Statin intolerance,
• MeSH
• Hyperlipidemias drug therapy   MeSH
• Cardiovascular Diseases drug therapy   MeSH
• Humans MeSH
• Myalgia chemically induced   MeSH
• Risk Factors MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage   adverse effects   therapeutic use   MeSH
• Drug Tolerance MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Hydroxymethylglutaryl-CoA Reductase Inhibitors MeSH

PURPOSE OF REVIEW: In our pilot study, we aimed to determine how many patients with the statin intolerance history referred to the specialized center for the diagnostics and treatment of lipoprotein metabolism disorders really suffer from a complete statin intolerance. The purpose of the study was to prove that complete statin intolerance is overestimated and overdiagnosed, and with the detailed knowledge of the issue and patient approach, it is possible to find an appropriate statin treatment for the most of patients. RECENT FINDINGS: With the increasing number of statin users worldwide, the issue of statin intolerance has been a frequently discussed topic in recent years. There are many factors that play a role in the manifestation of statin intolerance (predisposing factors as age, sex, and some diseases), genetic factors leading to a different metabolism, drug-drug interactions, psychological reasons, and the negative influence of the mass media. However, it is estimated that true complete statin intolerance, defined by an intolerance of at least three statins at their usual lowest daily doses, occurs in approximately 3-6% of all statin users. In our pilot study, we conducted a retrospective analysis of 300 patients who were referred to the Center of Preventive Cardiology with a history of statin intolerance. During the follow-up treatment, 222 patients (74%) were able to use some statin (rosu-, atorva-, simva-, fluvastatin), and in 21% of the cases (63 patient), the target values according their CV risk level were even achieved. Only 78 patients (26%) were confirmed as being complete statin intolerant following a thorough therapeutic effort. The most tolerated statin was rosuvastatin.

• Keywords
• Complete statin intolerance, Partial statin intolerance, Statin associated muscle symptoms,
• MeSH
• Cardiovascular Diseases prevention & control   MeSH
• Middle Aged MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Pilot Projects MeSH
• Primary Prevention MeSH
• Retrospective Studies MeSH
• Rosuvastatin Calcium adverse effects   MeSH
• Secondary Prevention MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Rosuvastatin Calcium MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors MeSH

BACKGROUND: Statin monotherapy for dyslipidemia only rarely achieves recommended target values of plasma lipids. Statin plus ezetimibe is a feasible treatment option. The aim of the present study was to test efficacy and safety of statin plus ezetimibe combination in the treatment of severe dyslipidemia in patients coming to an ordinary lipid and diabetology department. METHODS AND RESULTS: A retrospective evaluation of 3 months treatment in 82 dyslipidemia patients (25 male, 57 female) with unsatisfactory statin monotherapy results (average equivalent of 30 mg atorvastatin) was performed. Ezetimibe 10 mg per day was added to preceding treatment. The group included 26 diabetics type 2. The addition of ezetimibe resulted in statistically significant decrease of plasma total cholesterol (TC) (-21%), LDL-C (-28%), triacylglyceroles (TAG) (-26%) and HDL-C (-6%). The recommended values of LDL-C were achieved in 42% of patients. In the diabetic subgroup a significant decrease of TC (24%), LDL-C (33%) and TAG (18%) was observed. There was no significant decrease of HDL-C. The recommended value of LDL-C was achieved in 48% of diabetics. There were no unfavourable side effects. CONCLUSIONS: The addition of ezetimib in a dose of 10 mg in hyperlipidaemia patients who had not achieved the recommended target values of LDL-C resulted in a subsequent significant decrease of both TC and LDL-C. It also enabled to increase the number of patients achieving the recommended target plasma lipid values. The treatment was safe and was not associated with adverse effects.

• MeSH
• Anticholesteremic Agents administration & dosage   MeSH
• Atorvastatin MeSH
• Azetidines administration & dosage   MeSH
• Adult MeSH
• Ezetimibe MeSH
• Hyperlipidemias blood   drug therapy   MeSH
• Drug Therapy, Combination MeSH
• Heptanoic Acids administration & dosage   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lipids blood   MeSH
• Pyrroles administration & dosage   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Simvastatin administration & dosage   MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anticholesteremic Agents MeSH
• Atorvastatin MeSH
• Azetidines MeSH
• Ezetimibe MeSH
• Heptanoic Acids MeSH
• Lipids MeSH
• Pyrroles MeSH
• Simvastatin MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors MeSH

Statins are the most common drugs administered for patients with cardiovascular disease. However, due to statin-associated muscle symptoms, adherence to statin therapy is challenging in clinical practice. Certain nutraceuticals, such as red yeast rice, bergamot, berberine, artichoke, soluble fiber, and plant sterols and stanols alone or in combination with each other, as well as with ezetimibe, might be considered as an alternative or add-on therapy to statins, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. These nutraceuticals could exert significant lipid-lowering activity and might present multiple non-lipid-lowering actions, including improvement of endothelial dysfunction and arterial stiffness, as well as anti-inflammatory and antioxidative properties. The aim of this expert opinion paper is to provide the first attempt at recommendation on the management of statin intolerance through the use of nutraceuticals with particular attention on those with effective low-density lipoprotein cholesterol reduction.

• Keywords
• cardiovascular risk, dyslipidemia, nutraceuticals, position paper, statin intolerance,
• MeSH
• Dyslipidemias diet therapy   drug therapy   MeSH
• Clinical Studies as Topic MeSH
• Humans MeSH
• Dietary Supplements * MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Hydroxymethylglutaryl-CoA Reductase Inhibitors MeSH

INTRODUCTION: Statin intolerance (SI) occurs in patients with dyslipidemia treated with statins. Statin-associated symptoms have been reported, but the overall patient experience is poorly understood. No instruments are available to collect this patient experience. Our aim is to develop a patient survey to define SI from the patient's perspective, inform clinical practice, and identify potential patient characteristics and barriers associated with discontinuing treatment when statin-related difficulties are encountered. METHODS: We conducted qualitative concept elicitation interviews with 65 patients across 12 European study sites. A semi-structured qualitative interview guide was developed based on literature review and clinician interviews. Concept elicitation interviews with patients were used to describe the patient experience and develop the conceptual framework for the survey. RESULTS: Symptoms experienced by patients included muscle and non-muscle-related pain and discomfort; other muscle-related symptoms; gastrointestinal, cardiovascular, cold-like, fatigue-related, and sensory and systems symptoms; mood changes; and cognitive and memory problems. Impacts included limitations on general physical functioning; physical activities; social functioning; emotional impacts; sleep disturbances; decreased productivity; and increased healthcare use. Conceptual framework elements to support survey goals include demographic and clinical characteristics, health information and beliefs, statin side-effect history, symptom severity, and impact severity. CONCLUSIONS: Symptoms and impacts described by patients showed a wider range of symptoms and impacts than usually discussed clinically. The patient survey is designed to capture information from patients who experience difficulties with statin therapy and may be useful in identifying patients who are at higher risk for giving up or discontinuing their treatment. FUNDING: Amgen Inc.

• Keywords
• Cardiology, Dyslipidemia, Lipid-lowering therapy, Patient experience, Qualitative research, Statin, Survey,
• MeSH
• Anticholesteremic Agents adverse effects   therapeutic use   MeSH
• Pain chemically induced   MeSH
• Adult MeSH
• Dyslipidemias drug therapy   epidemiology   MeSH
• Qualitative Research MeSH
• Middle Aged MeSH
• Humans MeSH
• Surveys and Questionnaires MeSH
• Aged MeSH
• Patient Satisfaction statistics & numerical data   MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects   therapeutic use   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe epidemiology   MeSH
• Names of Substances
• Anticholesteremic Agents MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors MeSH

Although statin therapy has proven to be the cornerstone for prevention and treatment of cardiovascular disease (CVD), there are many patients for whom long-term therapy remains suboptimal. The aims of this article are to review the current complex issues associated with statin use and to explore when novel treatment approaches should be considered. Statin discontinuation as well as adherence to statin therapy remain two of the greatest challenges for lipidologists. Evidence suggests that between 40 and 75% of patients discontinue their statin therapy within one year after initiation. Furthermore, whilst the reasons for persistence with statin therapy are complex, evidence shows that low-adherence to statins negatively impacts clinical outcomes and residual CV risk remains a major concern. Non-adherence or lack of persistence with long-term statin therapy in real-life may be the main cause of inadequate low density lipoprotein cholesterol lowering with statins. There is a large need for the improvement of the use of statins, which have good safety profiles and are inexpensive. On the other hand, in a non-cost-constrained environment, proprotein convertase subtilisin/kexin type 9 inhibitors should arguably be used more often in those patients in whom treatment with statins remains unsatisfactory.

• Keywords
• Cardiovascular risk, Discontinuation, HDL-C, Non-adherence, PCSK9, Statin, Statin-associated muscle symptoms,
• MeSH
• Medication Adherence * MeSH
• Cholesterol, HDL antagonists & inhibitors   blood   MeSH
• Hypercholesterolemia blood   drug therapy   MeSH
• Cardiovascular Diseases blood   drug therapy   MeSH
• Humans MeSH
• Myalgia chemically induced   MeSH
• PCSK9 Inhibitors MeSH
• Sleep Wake Disorders chemically induced   MeSH
• Randomized Controlled Trials as Topic methods   MeSH
• Risk Factors MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects   therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Cholesterol, HDL MeSH
• PCSK9 Inhibitors MeSH
• PCSK9 protein, human MeSH Browser
• Hydroxymethylglutaryl-CoA Reductase Inhibitors MeSH

OBJECTIVES: Statins significantly reduce CV morbidity and mortality. Unfortunately, one of the side effects of statins is myopathy, for which statins cannot be administered in sufficient doses or administered at all. The aim of this study was to demonstrate the effect of coenzyme Q10 in patients with statin myopathy. DESIGN/SETTING: Twenty eight patients aged 60.6±10.7 years were monitored (18 women and 10 men) and treated with different types and doses of statin. Muscle weakness and pain was monitored using a scale of one to ten, on which patients expressed the degree of their inconvenience. Examination of muscle problems was performed prior to administration of CQ10 and after 3 and 6 months of dosing. Statistical analysis was performed using Friedman test, Annova and Students t-test. RESULTS: Pain decreased on average by 53.8% (p<0.0001), muscle weakness by 44.4% (p<0.0001). The CQ10 levels were increased by more than 194% (from 0,903 μg/ml to 2.66 μg/ml; p<0.0001). CONCLUSION: After a six-month administration of coenzyme Q10, muscle pain and sensitivity statistically significantly decreased.

• MeSH
• Cardiovascular Diseases drug therapy   MeSH
• Drug Therapy, Combination MeSH
• Middle Aged MeSH
• Humans MeSH
• Musculoskeletal Pain chemically induced   drug therapy   MeSH
• Aged MeSH
• Patient Satisfaction MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage   adverse effects   MeSH
• Muscle Weakness chemically induced   drug therapy   MeSH
• Ubiquinone administration & dosage   analogs & derivatives   MeSH
• Vitamins administration & dosage   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• coenzyme Q10 MeSH Browser
• Hydroxymethylglutaryl-CoA Reductase Inhibitors MeSH
• Ubiquinone MeSH
• Vitamins MeSH

AIM: Genetic variants affecting statin uptake, metabolism or predisposing to muscular diseases may confer susceptibility to statin-induced myopathy. Besides the SLCO1B1 rs4149056 genotype, common genetic variants do not seem to determine statin-associated myopathy. Here we aimed to address the potential role of rare variants. METHODS: We performed whole exome sequencing in 88 individuals suffering from statin-associated myopathy and assessed the burden of rare variants using candidate-gene and exome-wide association analysis. RESULTS: In the novel candidate gene CLCN1, we identified a heterozygote truncating mutation p.R894* in four patients. In addition, we detected predictably pathogenic case-specific variants in MYOT, CYP3A5, SH3TC2, FBXO32 and RBM20. CONCLUSION: These findings support the role of rare variants and nominate loci for follow-up studies.

• Keywords
• CLCN1, atorvastatin, gene, myopathy, rosuvastatin, simvastatin, statin,
• MeSH
• Genome-Wide Association Study MeSH
• Chloride Channels genetics   MeSH
• Adult MeSH
• Exome genetics   MeSH
• Genetic Variation MeSH
• Genotype MeSH
• Middle Aged MeSH
• Humans MeSH
• Muscular Diseases chemically induced   epidemiology   genetics   MeSH
• Liver-Specific Organic Anion Transporter 1 genetics   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects   MeSH
• Rare Diseases genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Chloride Channels MeSH
• CLC-1 channel MeSH Browser
• Liver-Specific Organic Anion Transporter 1 MeSH
• SLCO1B1 protein, human MeSH Browser
• Hydroxymethylglutaryl-CoA Reductase Inhibitors MeSH

This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) in order to calculate the effect size of statin therapy in changing plasma cortisol concentrations. Following a systematic search in Medline, SCOPUS, Web of Science and Google Scholar databases (by up to March 01, 2015), 7 eligible RCTs were selected. Random-effects meta-analysis suggested a significant increase in plasma cortisol concentrations following statin therapy (WMD: 6.34%, 95% CI: 1.80, 10.87, p=0.006). Subgroup analysis confirmed the significance of the effect with lipophilic statins comprising atorvastatin, simvastatin, and lovastatin (WMD: 7.00%, 95% CI: 2.21, 11.79, p=0.004) but not with hydrophilic statins (rosuvastatin and pravastatin) (WMD: 0.60%, 95% CI: -13.46, 14.66, p=0.933). In the meta-regression analysis, changes in plasma cortisol concentrations following statin therapy were found to be independent of treatment duration. Results of this meta-analysis of RCTs suggest a significant elevation in plasma cortisol levels following statin therapy.

• Keywords
• Cortisol level, Meta-analysis, Randomized controlled trial, Statin,
• MeSH
• Hydrocortisone blood   MeSH
• Humans MeSH
• Randomized Controlled Trials as Topic MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology   therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Review MeSH
• Systematic Review MeSH
• Names of Substances
• Hydrocortisone MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors MeSH

BACKGROUND AND PURPOSE: Statins reduce stroke risk when initiated months after transient ischemic attack (TIA)/stroke and reduce early vascular events in acute coronary syndromes, possibly via pleiotropic plaque stabilization. Few data exist on acute statin use in TIA. We aimed to determine whether statin pretreatment at TIA onset modified early stroke risk in carotid stenosis. METHODS: We analyzed data from 2770 patients with TIA from 11 centers, 387 with ipsilateral carotid stenosis. ABCD2 score, abnormal diffusion weighted imaging, medication pretreatment, and early stroke were recorded. RESULTS: In patients with carotid stenosis, 7-day stroke risk was 8.3% (95% confidence interval [CI], 5.7-11.1) compared with 2.7% (CI, 2.0%-3.4%) without stenosis (P<0.0001; 90-day risks 17.8% and 5.7% [P<0.0001]). Among carotid stenosis patients, nonprocedural 7-day stroke risk was 3.8% (CI, 1.2%-9.7%) with statin treatment at TIA onset, compared with 13.2% (CI, 8.5%-19.8%) in those not statin pretreated (P=0.01; 90-day risks 8.9% versus 20.8% [P=0.01]). Statin pretreatment was associated with reduced stroke risk in patients with carotid stenosis (odds ratio for 90-day stroke, 0.37; CI, 0.17-0.82) but not nonstenosis patients (odds ratio, 1.3; CI, 0.8-2.24; P for interaction, 0.008). On multivariable logistic regression, the association remained after adjustment for ABCD2 score, smoking, antiplatelet treatment, recent TIA, and diffusion weighted imaging hyperintensity (adjusted P for interaction, 0.054). CONCLUSIONS: In acute symptomatic carotid stenosis, statin pretreatment was associated with reduced stroke risk, consistent with findings from randomized trials in acute coronary syndromes. These data support the hypothesis that statins started acutely after TIA symptom onset may also be beneficial to prevent early stroke. Randomized trials addressing this question are required.

• Keywords
• carotid stenosis, ischemic attack, transient, statin,
• MeSH
• Time Factors MeSH
• Stroke diagnostic imaging   physiopathology   prevention & control   MeSH
• Diffusion Magnetic Resonance Imaging methods   MeSH
• Brain Ischemia diagnostic imaging   drug therapy   physiopathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Radiography MeSH
• Risk Factors MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage   MeSH
• Carotid Stenosis diagnostic imaging   drug therapy   physiopathology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• Hydroxymethylglutaryl-CoA Reductase Inhibitors MeSH