The Targeting of Native Proteins to the Endoplasmic Reticulum-Associated Degradation (ERAD) Pathway: An Expanding Repertoire of Regulated Substrates. Given the benefits of statins in ASCVD risk reduction, clinicians should partner with the patient to gain a thorough symptom history and determine if he or she is truly statin intolerant. Ward NC, Watts GF, Eckel RH. Statin intolerance is defined as one or more adverse effects associated with statin therapy which resolves or improves with dose reduction or discontinuation and can be classified as a complete inability to tolerate any dose of a statin or partial intolerance with inability to tolerate the dose necessary to achieve the patient-specific therapeut. Roadblocks Ask the patient to identify barriers or impediments to quitting. Once symptoms have resolved, start a low dose of a different statin. peripheral arterial disease presumed to be of atherosclerotic origin. Or (800) 253-4636 The most common complaints are various muscle symptoms (soreness, aches, weakness, cramps) typically affecting symmetrical, large, and proximal muscle groups usually without creatine kinase (CK) elevation.7 Very rarely, myopathy or rhabdomyolysis may occur at a rate of 1 in 10,000 patients per year, simvastatin being the most commonly implicated statin.8,9, Other adverse signs or symptoms include liver toxicity and dysglycemia.10 The mechanism by which statins cause muscle symptoms is poorly understood but not thought to be always directly attributable to statin use. The ODYSSEY ALTERNATIVE trial19 compared PCSK9 inhibitor therapy (using alirocumab) with ezetimibe in patients with confirmed statin intolerance. The .gov means its official. Boldface typeindicates specific statins and doses that were evaluated in RCTs (1617,1846,4748,49) included in CQ1, CQ2, and the Cholesterol Treatment Trialists 2010 meta-analysis included in CQ3 (20). Epub 2018 Apr 6. The https:// ensures that you are connecting to the Other factors may be considered: LDL-C 160 mg/dL, family history of premature cardiovascular disease, hs-CRP 2.0 The risk of very serious side effects is extremely low. Effect of statins on skeletal muscle function. D. In individuals intolerant of the recommended intensity of statin therapy, use the maximally-tolerated intensity of statin. Can J Physiol Pharmacol. Solved Statin intolerance is a problem that prevents or - Chegg While the risk estimate is applied to individuals, it is based on group averages. As the name suggests, statin intolerance occurs when a patient is unable to continue to use a statin, either because of the development of a side effect or because of evidence on a blood test that certain markers of liver function or muscle function (creatine kinase) are sufficiently abnormal to cause concern. For those in whom a risk assessment is uncertain, consider factors such as primary LDL-C 160 mg/dL or other evidence of genetic hyperlipidemias, family history of premature ASCVD with onset <55 years of age in a first-degree male relative or <65 years of age in a first-degree female relative, hs-CRP >2 mg/L, CAC score 300 Agatston units, or 75th percentile for age, sex, and ethnicity (for additional information, see http://www.mesa-nhlbi.org/CACReference.aspx), ABI <0.9, or lifetime risk of ASCVD. Although similar rates of myalgia were reported initially in both atorvastatin and placebo groups (hazard ratio [HR] 1.34; 95% CI 1.051.71; P = .02), after full completion of the washout and double-crossover protocol, significantly more patients experienced muscle-related symptoms when taking atorvastatin than when taking placebo (HR 1.96; 95% CI 1.442.66; P < .001). An important issue in the management of patients with statin intolerance/statin-associated muscle symptoms is the need to avoid statin discontinuation. How much have muscle symptoms impacted everyday activities? For those with unknown baseline LDL-C, an LDL-C <100 mg/dL was observed in RCTs of high-intensity statin therapy. Statin-associated muscle symptoms: impact on statin therapyEuropean Atherosclerosis Society consensus panel statement on assessment, aetiology and management. In a nonfasting individual, a non-HDLC >220 mg/dL may indicate genetic hypercholesterolemia that requires further evaluation or a secondary etiology. Primary prevention - Diabetes 40-75 years of age and LDL-C 70-189 mg/dL, b. Prevalence of Statin Intolerance: a meta-analysis. - ResearchGate Stroes ES, Thompson PD, Corsini A, et al. Use this apps Evaluate tab for help. 1. Along with hypertension, diabetes, and smoking, hyperlipidemia has consistently been shown to be one of the most significant and modifiable risk factors of coronary artery disease development and progression.2. cannot work, sleep, perform household chores, or climb stairs). injury; COR, Class of Recommendation; HDL-C, high-density lipoprotein cholesterol; hs-CRP, high-sensitivity C-reactive protein; LDL-C, low-density The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Statin therapy is not routinely recommended for individuals with NYHA class II-IV heart failure or who are receiving maintenance (III A), CK should not be routinely measured in individuals receiving statin therapy. Federal government websites often end in .gov or .mil. Jacobson TA, Cheeley MK, Jones PH, et al. Increase statin intensity, or if on maximally-tolerated statin intensity, consider addition of nonstatin therapy in selected high-risk The division of lifetime risk by these 5 strata leads to thresholds in the data with large apparent changes in lifetime risk estimates. Italic type indicates statins and doses that are approved by the FDA but have not been tested in the RCTs reviewed. All rights reserved. Continue with current statin prescription. Saved Stories. b. Efficacy and tolerability of evolocumab vs ezetimibe in patients with muscle-related statin intolerance: the GAUSS-3 randomized clinical trial. official website and that any information you provide is encrypted Intermittent rather than daily dosing can also be considered for patients with statin-associated muscle symptoms and for patients who have a history of severe myotoxicities and marked creatine kinase elevation. Statin intolerance exists as a spectrum of muscle related symptoms, which may or may not be related to statin therapy directly, and a significant nocebo effect (perceived symptoms). This substantial difference in lifetime risk is due to the fact that they are in different stratum. Has the patient had muscle pain while taking a previous statin? f. Regularly monitor adherence to lifestyle and drug therapy every 3-12 mo once adherence has been established. Persian Cats: What to Know - WebMD Prescribe a calorie-restricted diet for obese or overweight individuals who would benefit from weight loss, based on the patient's preferences and health status, and preferably refer to a nutrition professional for counseling. Characteristics predisposing individuals to statin adverse effects include, but are not limited to: Additional characteristics that may modify the decision to use higher statin intensities may include, but are not limited to: It is reasonable to evaluate and treat muscle symptoms, including pain, tenderness, stiffness, cramping, weakness, or fatigue, in statin-treated patients according to the following management algorithm: (IIa B). Standard CK ranges may vary by lab. Do not routinely monitor ALT or CK unless symptomatic, c. Screen and treat type 2 diabetes according to current practice guidelines. The 10-year calculated ASCVD risk is a quantitative estimation of absolute risk based upon data from representative population samples. (For purposes of this app, prescribing information was last accessed on 2/4/2015 through pharmaceutical company websites. Click here for 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk, Click here for 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Click here for 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults, Click here for 2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk, Click here for 2008 AHRQ Guideline on Treating Tobacco Use and Dependence, Click here for ACC Dyslipidemia Clinical Community, Click here for ACC Cardiometabolic Clinical Community, Click here for Blood Cholesterol Guideline, Please go to cardiosmart.org to find more information about how to prevent, treat, and manage cardiovascular disease. Many patients . Use the following points to discuss patients preferences and ability to comply with treatment. Factors that increase risk for statin symptoms, Possible predispositions to muscle symptoms. Multiple or serious comorbidities, including impaired renal or hepatic function. of age in a first-degree male relative or <65 years of age in a first-degree female relative; hs-CRP 2 mg/L; CAC score 300 Agatston units or 75 th percentile for age, sex, and ethnicity; ABI <0.9; or Management of Statin Intolerance in 2018: Still More Questions Than (I A), In individuals with clinical ASCVD in whom high-intensity statin therapy would otherwise be used, when high-intensity statin therapy is contraindicated or when characteristics predisposing to statin-associated adverse effects are present, moderate-intensity statin should be used as the second option if tolerated. These are one of the safest hypolipidemic drugs but many patients are bound to discontinue statins due to their side effects. and transmitted securely. Discontinuation of statins leads to dylipidemia and its grave consequences. Long, J., What to Do When the Patient Cannot Tolerate Statins: Alternative Therapies Proceedings of the American College of Cardiology Scientific Sessions 2013. J of Clinical Lipidology. Statin-induced myalgia [8] is a major cause of statin intolerance [9][10][11] [12] [13] and is common; it is reported in 27% of subjects treated with statins. J Pharm Bioallied Sci. Copyright 2023 The Cleveland Clinic Foundation. Rule out secondary causes of hyperlipidemia, c. Achieve at least a 50% reduction in LDL-C, d. LDL-C lowering nonstatin therapy may be considered to further reduce LDL-C, 3. Careers. Some estimate that up to 20% of patients are unable to tolerate statin therapy owing to muscle symptoms.4. NLA scientific statement on statin intolerance: a new definition and key considerations for ASCVD risk reduction in the statin intolerant patient. Statin intolerance refers to a spectrum of adverse symptoms and signs experienced by patients associated with statin therapy. Mayo Clinic defines standard CK levels as: Severe CK elevation, with possible indication for rhabdomyolysis, may be considered to be > 5x ULN. Statin intolerance: Now a solved problem - ResearchGate 2019 Sep;49(9):1081-1091. doi: 10.1111/imj.14429. The 2022 NLA scientific statement on statin intolerance provides an updated definition of statin intolerance which now classifies intolerance as either partial or complete, taking into consideration the ability to achieve therapeutic targets on maximally tolerated statin dosing. mg/L, CAC score 300 Agaston units, ABI <0.9 or lifetime ASCVD risk, 5. Liver dysfunction, a rare finding in patients taking high-intensity statins, appears to be a laboratory side effect but is not clinically significant.14 Liver failure is even more rare.15 There is a slight increase in diabetes in patients taking statin therapy, but this should be weighed against far greater risk reductions in major cardiovascular events. (ACC AF guideline refernece), http://www.medsafe.govt.nz/profs/PUArticles/March2014StatinsAndCYPInteractions.htm, http://www.fda.gov/Drugs/DrugSafety/ucm293877.htm, **http://www.pharmacologyweekly.com/articles/statin-administration-evening-night-bedtime, II Studies show that the most hydrophilic statins were least likely to cause myalgia, whereas the most lipophilic ones were most likely to be associated with muscular adverse effects (4).http://care.diabetesjournals.org/content/36/Supplement_2/S325.full. The 10-year risk estimate for "optimal risk factors" is represented by the following specific risk factor numbers for an individual of the same age, sex and race: Total cholesterol of 170 mg/dL, HDL-cholesterol of 50 mg/dL, untreated systolic blood pressure of 110 mm Hg, no diabetes history, and not a current smoker. The absolute reduction in ASCVD events from moderate- or high-intensity statin therapy can be approximated by multiplying the estimated 10-year ASCVD risk by the anticipated relative risk reduction from the intensity of statin initiated (~30% for moderate-intensity statin or ~45% for high-intensity statin therapy). The GAUSS-3 trial18 used a double-crossover design with atorvastatin and placebo in 491 patients who were self-reported to be intolerant to 2 or more statins. Follow-Up Follow steps to treat and manage possible statin-related muscle symptoms. age, family history of statin intolerance, renal function, liver disease). Biochim Biophys Acta Mol Cell Biol Lipids. Tolerability of red yeast rice (2,400 mg twice daily) versus pravastatin (20 mg twice daily) in patients with previous statin intolerance. Primary LDL-C 160 mg/dL or other evidence of genetic hyperlipidemias, High sensitivity C-reactive protein 2 mg/L, Coronary artery calcium score 300 Agatston units or 75th percentile for age, sex, and ethnicity. Statin Intolerance: What did you do? Statin Intolerance Clinical Guide 2018 - PMC - National Center for National Library of Medicine (I A), Advise adults with a BMI 40 kg/m2 or BMI 35 kg/m2 with obesity-related co-morbid conditions who are motivated to lose weight and who have not responded to behavioral treatment with or without pharmacotherapy with sufficient weight loss to achieve targeted health outcome goals that bariatric surgery may be an appropriate option to improve health and offer referral to an experienced bariatric surgeon for consultation and evaluation. (I A), Prescribe on site, high-intensity (i.e., >14 sessions in 6 months) comprehensive weight loss interventions provided in individual or group sessions by a trained interventionist. Evaluate possible intolerance to patient's current statin prescription. Statin intolerance: now a solved problem - PubMed If mild to moderate muscle symptoms develop during statin therapy: Discontinue the statin until the symptoms can be evaluated. Elnaem MH, Mohamed MHN, Huri HZ, Azarisman SM, Elkalmi RM. Tobacco users who have failed in previous quit attempts should be told that most people make repeated quit attempts before they are successful. Statin intolerance: new data and further options for treatment Options include step-by-step reduction of the statin dose (dechallenge), switching to a different statin, or using intermittent dosages (alternate-day therapy). (I A), High-intensity statin therapy is reasonable for adults 40 to 75 years of age with diabetes mellitus with a 7.5% estimated 10-year ASCVD risk unless contraindicated. Biochim Biophys Acta Mol Cell Biol Lipids. Use of this website is subject to the website terms of use and privacy policy. "Mild to Moderate Muscular Symptoms with High-Dosage Statin Therapy in Hyperlipidemic Patients The PRIMO Study." Statins, one of the most extensively studied drugs on the planet, taken by tens of millions of Americans alone, have long had a perplexing side effect. *Fasting lipid panel preferred. These medications have also been linked to a lower risk of heart disease and stroke. Clinician-Patient discussion determined preference for trying different statin. Hence, there should be enough strategies for statin intolerant patients, so that they can be saved from these consequences. 8600 Rockville Pike A. Heart-healthy lifestyle habits should be encouraged for all individuals. Statin intolerance is widely reported in clinical practice, often leading to its discontinuation. Baseline investigations for liver function and muscle toxicity should be done before initiating statin therapy. Statin Intolerance: What Are the Symptoms? - Healthline Evidence from 1 RCT only: down-titration if unable to tolerate atorvastatin 80 mg in the IDEAL (Incremental Decrease through Aggressive Lipid Lowering) study (47). adherence to lifestyle and drug therapy with lipid and safety assessments. Statin intolerance: Now a solved problem; Author . My Research and Language Selection Sign into My Research Create My Research Account English; Help and support. Evaluate the potential for ASCVD risk reduction benefits, adverse effects, drug-drug interactions, and consider patient preferences. Proceed with one of the following as appropriate: A. In a patient suspected of having statin intolerance, statin therapy should be discontinued and symptoms monitored over two weeks to see if they resolve. Statin intolerance: Now a solved problem - DOAJ Follow steps to treat and manage possible statin-related muscle symptoms. These are one of the safest. All Rights Reserved. If patient was already taken off original statin, follow up to see if symptoms have resolved. Statin intolerance: now a solved problem. - Abstract - Europe PMC All rights reserved. Changing from a lipophilic to a hydrophilic statin is a reasonable first-line alternative drug strategy for patients experiencing myalgia. A review of the manufacturer's prescribing information may be useful before initiating any cholesterol-lowering drug. ACCs Statin Intolerance App uses clinical guidelines and best practices to help clinical professionals. potential drug interactions and dose adjustment according to patho . Problems With Persistence. Nonmuscle-related side effects have also been attributed to statin therapy, several of which have been studied. lifetime risk of ASCVD. Statin Toxicity. Wei MY, Ito MK, Cohen JD, Brinton EA, Jacobson TA. Whereas previous trials have suggested an almost indistinguishable side-effect profile between low-dose statin therapy and placebo, more recently designed rechallenge crossover studies such as the Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects 3 (GAUSS-3)18 and the ODYSSEY ALTERNATIVE19 trials have been able to establish statin intolerance as a real and verifiable phenomenon. 3 Statins are the most widely prescribed and evidence-based lipid-lowering drug in the world for lowering LDL-c and reducing cardiovascular morbidity and mortality, both in primary and seconda. One is good,. Statin intolerance: now a solved problem - citationimpact.com Next Follow-Up: Patient was taken off the original statin, Next Follow-Up: Patient was rechallenged with the original statin, Next Follow-Up:Considering starting patient on alternative statin, Next Follow-Up: Muscle symptoms returned on alternative statin, http://www.pharmacologyweekly.com/articles/statin-administration-evening-night-bedtime, http://care.diabetesjournals.org/content/36/Supplement_2/S325.full, Click here for Definitions of Statin Intensity, https://itunes.apple.com/us/app/acc-guideline-clinical-app/id931723742?mt=8, https://play.google.com/store/apps/details?id=com.bbi.accorg.cardiosource.american_college_of_cardiology&hl=en, https://itunes.apple.com/us/app/ascvd-risk-estimator/id808875968?mt=8, https://play.google.com/store/apps/details?id=org.acc.cvrisk&hl=en, http://tools.cardiosource.org/ASCVD-Risk-Estimator/. While the frequency of symptoms was higher on atorvastatin, less than half of patients reported symptoms while taking atorvastatin but not while taking placebo, further substantiating that the nocebo effect contributes significantly to reported statin intolerance.13. NLA scientific statement on statin intolerance: a new definition and key considerations for ASCVD risk reduction in the statin intolerant patient. Potential adverse effects, and druginteractions. Support Center Find answers to questions about products, access, use, setup, and administration. In summary, the updated NLA scientific statement provides a novel definition of the syndrome, separating intolerance into partial or complete as defined by ability to achieve therapeutic targets with maximally tolerated dosing. To determine whether to initiate a statin, engage in a clinician-patient discussion of the potential for ASCVD risk reduction, adverse