Guideline sources The following summarized guidelines for the evaluation and management of dyslipidemia are prepared by our editorial team based on guidelines from the American Diabetes Association (ADA 2023), the Canadian Pediatric Cardiology Association (CPCA/CCS 2022), the Heart Failure Society of America (HFSA/AHA/ACC 2022), the Canadian Cardiovascular Society (CCS 2021; 2018; 2016), the European Society of Cardiology (ESC 2021), the Endocrine Society (ES 2020), the European Society of Cardiology (ESC/EAS 2020), the United States Department of Defense (DoD/VA 2020), the American College of Preventive Medicine (ACPM/ADA/PCNA/ABC/ASPC/AAPA/AGS/AHA/ACC/APhA 2019), the U.S. Preventive Services Task Force (USPSTF 2016), and the Society of Cardiovascular Computed Tomography (SCCT 2013). 1 2 3 4 5 6 7 8 9 10 12 13 14 15 15 16 17 18 Definition Dyslipidemia is a disorder of lipid metabolism characterized by elevated LDL cholesterol, decreased HDL cholesterol and/or increased triglycerides, which contributes to the development of atherosclerosis. 15 Epidemiology https://web.pathway.md/diseases/receTcWVpm18Q5oo1 1/19 6/29/23, 10:23 PM Dyslipidemia Pathway p gy Primary dyslipidemia is due to genetic abnormalities, whereas secondary dyslipidemia is multifactorial, and is associated with obesity, physical inactivity, high-carbohydrate and high-fat diets, smoking, alcohol use, uncontrolled diabetes mellitus, hypothyroidism, renal failure, cholestatic liver disease, nephrotic syndrome, and various drugs (corticosteroids, progestogens, androgenic steroids, thiazide diuretics, beta blockers, oral estrogens, retinoic acid derivatives). 15 Pathophysiology In the United States, an estimated 53% of adults have at least one lipid abnormality: 27% have elevated LDL cholesterol, 23% have decreased HDL cholesterol, and 30% have increased triglycerides. 16 Disease course Lipid abnormalities contribute to the formation of atherosclerotic plaque, leading to an increased risk of CVD, stroke, and peripheral arterial disease. 17 Prognosis and risk of recurrence Treatment with statins is associated with a relative reduction in the risk of major adverse vascular events of 22% in men and 16% in women for every 1.0 mmol/L (38.6 mg/dL) reduction in LDL cholesterol. 18 Calculator DLCN criteria for familial hyperc Guidelines 1. Screening and diagnosis Indications for screening, adults: As per CCS 2021 guidelines: Obtain non-HDL cholesterol or ApoB over LDL cholesterol as the preferred lipid parameter for screening in any patient with triglycerides > 1.5 mmol/L. A Measure lipoprotein(a) level once in a person's lifetime as a part of the initial lipid screening. A As per PCNA/ASPC/APhA/AGS/ADA/ACPM/ABC/AAPA/ACC/AHA 2019 guidelines: Measure a fasting or a nonfasting plasma lipid profile to estimate CVD risk and document baseline LDL cholesterol in adult patients 20 years old not being on lipid-lowering therapy. B Consider measuring fasting lipid profile in adult patients 20 years old with a family history of premature atherosclerotic vascular disease or genetic hyperlipidemia, in order to aid in https://web.pathway.md/diseases/receTcWVpm18Q5oo1 2/19 6/29/23, 10:23 PM Dyslipidemia Pathway the understanding and identification of familial lipid disorders. C As per CCS 2016 guidelines: Screen for dyslipidemia with nonfasting lipid and lipoprotein testing in adult patients undergoing cardiovascular risk assessment. A Complete a cardiovascular risk assessment every 5 years in patients 40-75 years old using the modified Framingham Risk Score or Cardiovascular Life Expectancy Model. A Indications for screening (pediatrics): insufficient evidence to assess the risks and benefits of screening for lipid disorders in pediatric and adolescent individuals (< 20 years old). I 2. Classification and risk stratification Risk assessment: as per ESC 2020 guidelines, obtain total risk estimation using a risk estimation system such as SCORE in asymptomatic patients > 40 years old without evidence of CVD, diabetes mellitus, CKD or hypercholesterolemia, or with LDL cholesterol level of > 190 mg/dL (> 4.9 mmoI/L). B Show 4 more 3. Diagnostic investigations Lipid profile, tests: As per EAS/ESC 2020 guidelines, obtain LDL cholesterol as the primary lipid analysis method for screening, diagnosis, and management. B Show 4 more As per PCNA/ASPC/APhA/AGS/ADA/ACPM/ABC/AAPA/ACC/AHA 2019 guidelines: Measure either a fasting or a nonfasting plasma lipid profile in 20 years old patients and not on lipid-lowering therapy to estimate ASCVD risk and to document baseline LDL cholesterol. B Consider measuring direct LDL cholesterol or modified LDL cholesterol estimate to improve accuracy over the Friedewald formula, in adult patients with a LDL cholesterol level < 70 mg/dL (< 1.8 mmol/L). C As per CCS 2016 guidelines, consider using non-HDL cholesterol levels as an alternative to LDL cholesterol for the evaluation of cardiovascular risk in adult patients. B Lipid profile, fasting state: As per PCNA/ASPC/APhA/AGS/ADA/ACPM/ABC/AAPA/ACC/AHA 2019 guidelines, consider obtaining a repeat lipid profile in the fasting state in patients with an initial nonfasting lipid profile showing triglyceride levels 400 mg/dL ( 4.5 mmol/L). B As per CCS 2016 guidelines, consider measuring lipid and lipoprotein levels in the fasting state in patients with a history of triglyceride levels > 400 mg/dL (> 4.5 mmol/L). C Apolipoprotein B: As per ESC 2020 guidelines, obtain ApoB for risk assessment particularly in patients with: high triglycerides levels very low LDL cholesterol levels https://web.pathway.md/diseases/receTcWVpm18Q5oo1 3/19 6/29/23, 10:23 PM Dyslipidemia Pathway metabolic syndrome obesity. B Show 2 more As per CCS 2016 guidelines, consider using ApoB levels as an alternative to LDL cholesterol for the evaluation of cardiovascular risk in adult patients. B Lipoprotein, a: As per EAS/ESC 2020 guidelines: Consider obtaining lipoprotein(a) at least once in each adult person's lifetime to identify patients with very high inherited lipoprotein(a) levels > 180 mg/dL (> 430 mmol/L) having a lifetime risk of ASCVD equivalent to the risk associated with heterozygous familial hypercholesterolemia. C Consider obtaining lipoprotein(a) in selected patients with a family history of premature CVD, and for reclassification in patients at borderline between moderate and high risk. C As per CCS 2016 guidelines, consider using lipoprotein A levels to refine risk assessment in patients with an intermediate Framingham Risk Score, or a family history of premature coronary artery disease. C Screening for hypothyroidism: evaluate for and rule out hypothyroidism as the cause of hyperlipidemia before initiating lipid-lowering therapy in patients with hyperlipidemia. A Screening for anabolic steroid use: obtain clinical or biochemical evaluation for anabolic steroid abuse in patients with low high-density lipoprotein (< 30 mg/dL; 0.8 mmol/L), especially in the absence of hypertriglyceridemia. E Coronary computed tomography: As per CCS 2021 guidelines, consider obtaining CAC screening using CT in asymptomatic adults 40 years of age and at intermediate risk (Framingham Risk Score 10-20%), if treatment decisions are uncertain. B Show 2 more As per ESC 2020 guidelines, consider obtaining coronary CT for the assessment of CAC score as a risk modifier in the cardiovascular risk assessment in asymptomatic patients at low or moderate risk. C As per SCCT 2013 guidelines, avoid obtaining CAC scoring for screening purposes in low- risk asymptomatic individuals, except in those with a family history of premature coronary artery disease. D Arterial ultrasound: consider obtaining arterial ultrasound to assess arterial (carotid and/or femoral) plaque burden as a risk modifier in patients at low or moderate risk. C 4. Medical management Treatment targets: As per ESC 2020 guidelines, consider targeting LDL cholesterol level of < 116 mg/dL (< 3.0 mmol/L) in low risk patients. B Show 3 more As per CCS 2016 guidelines, use a treat-to-target approach to mitigate the risk of CVD. B https://web.pathway.md/diseases/receTcWVpm18Q5oo1 4/19 6/29/23, 10:23 PM Dyslipidemia Pathway Show 2 more Statins: As per CCS 2021 guidelines, initiate high-intensity statin therapy in addition to appropriate health behavior modifications for secondary prevention in patients with CVD. Administer the maximally tolerated statin dose in patients not tolerating a high-intensity statins. A As per ESC 2020 guidelines, initiate a high-intensity statin up to the highest tolerated dose to reach the goals set for the specific level of risk. A As per AHA 2019 guidelines, consider using CAC score in the decision to withhold, postpone or initiate statin therapy in intermediate risk or selected borderline risk adult patients, if the decision about statin use remains uncertain. C Show 4 more As per CCS 2016 guidelines, initiate statin therapy in patients with the following high risk conditions to decrease the risk of CVD events and mortality: clinical atherosclerosis AAA most cases of diabetes mellitus CKD (> 50 years old patients) LDL cholesterol 190 mg/dL ( 5.0 mmol/L). A Show 4 more Ezetimibe: As per CCS 2021 guidelines, intensify lipid-lowering therapy with ezetimibe and/or PCSK9 inhibitor therapy for secondary prevention in all patients with CVD, if LDL cholesterol remains 1.8 mmol/L (or non-HDL cholesterol 2.4 mmol/L or ApoB 0.7 g/L) while receiving the maximally tolerated statin dose. A Landmark trials: IMPROVE-IT In patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg/dL, simvastatin- ezetimibe was superior to simvastatin monotherapy once daily with respect to death from cardiovascular causes, major coronary event, or nonfatal stroke, Kaplan-Meier event rate at 7 years. Cannon CP et al. N Engl J Med. 2015 Jun 18. As per ESC 2020 guidelines: Add ezetimibe to statins if the goals are not achieved with the maximum tolerated dose of statins. B Consider initiating ezetimibe if statins are not tolerated at any dosage, even after rechallenge. C PCSK9 inhibitors: As per CCS 2021 guidelines: https://web.pathway.md/diseases/receTcWVpm18Q5oo1 5/19 6/29/23, 10:23 PM Dyslipidemia Pathway Intensify lipid-lowering therapy with a PCSK9 inhibitor (evolocumab or alirocumab) with or without the additional use of ezetimibe for secondary prevention in patients with CVD shown to derive the largest benefit from PCSK9 inhibitor therapy, if LDL cholesterol remains 1.8 mmol/L (or non-HDL cholesterol 2.4 mmol/L or ApoB 0.7 g/L) while receiving the maximally tolerated statin dose. B Intensify lipid-lowering therapy with a PCSK9 inhibitor and/or ezetimibe for secondary prevention in all patients with CVD, if LDL cholesterol remains 1.8 mmol/L (or non-HDL cholesterol 2.4 mmol/L or ApoB 0.7 g/L) while receiving the maximally tolerated statin dose. Initiate PCSK9 inhibitor therapy if ezetimibe is used initially and LDL cholesterol remains 1.8 mmol/L (or non-HDL cholesterol 2.4 mmol/L or ApoB 0.7 g/L). A Updated evidence: FOURIER-OLE In patients with a history of established ASCVD and a fasting low-density lipoprotein cholesterol level 70 mg/dL while on statin, evolocumab was superior to placebo in parent study with respect to the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. Michelle L O'Donoghue et al. Circulation. 2022 Oct 11. As per ESC 2020 guidelines, consider adding PCSK9 inhibitor for primary prevention in very high risk patients if the LDL cholesterol goal is not achieved with a maximum tolerated dose of a statin and ezetimibe. C Show 2 more Landmark trials: FOURIER In patients with ASCVD and LDL cholesterol 70 mg/dL (1.8 mmol/L) who were receiving statin therapy, evolocumab was superior to placebo with respect to major cardiovascular events. Sabatine MS et al. N Engl J Med. 2017 May 4. Icosapent ethyl: As per CCS 2021 guidelines, initiate icosapent ethyl to decrease the risk of cardiovascular events in patients with ASCVD or with diabetes and 1 cardiovascular risk factors having an elevated fasting triglyceride level of 1.5-5.6 mmol/L despite treatment with maximally tolerated statin therapy. A As per VA 2020 guidelines: Consider offering icosapent ethyl for secondary prevention to reduce cardiovascular morbidity and mortality in patients on statin therapy with persistently elevated fasting triglycerides > 150 mg/dL. C Insufficient evidence to recommend for or against icosapent ethyl for primary prevention in patients on statin therapy with persistently elevated fasting triglycerides. I Fibrates: https://web.pathway.md/diseases/receTcWVpm18Q5oo1 6/19 6/29/23, 10:23 PM Dyslipidemia Pathway As per VA 2020 guidelines, avoid adding fibrates to statins for primary or secondary prevention. D As per CCS 2016 guidelines, avoid using fibrates to prevent cardiovascular events in patients achieved LDL cholesterol targets on statin therapy. D Bile acid sequestrants: As per ESC 2020 guidelines, consider adding a bile acid sequestrant if the goal is not achieved with statins. C As per CCS 2016 guidelines, consider initiating bile acid sequestrants to lower LDL cholesterol in high-risk patients with LDL cholesterol levels remaining above target despite statin treatment with or without ezetimibe therapy. C Niacin: As per VA 2020 guidelines, avoid using niacin (supplements or prescriptions) for primary or secondary prevention. D As per CCS 2016 guidelines, avoid using niacin to prevent CVD in patients achieved LDL cholesterol targets with statin therapy. D Bempedoic acid: insufficient evidence to recommend for or against using bempedoic acid with or without statins for either primary or secondary prevention. I Updated evidence: CLEAR Outcomes In patients who were unable or unwilling to take statins owing to unacceptable adverse effects and had or were at high risk for CVD, bempedoic acid was superior to placebo with respect to major adverse cardiovascular events. Steven E Nissen et al. N Engl J Med. 2023 Apr 13. 5. Nonpharmacologic interventions Dietary modifications: As per VA 2020 guidelines, advise following a dietitian-led Mediterranean diet for primary and secondary prevention of CVD. B As per CCS 2016 guidelines, advise all patients to follow healthy eating and adopt the Mediterranean dietary pattern in order to reduce cardiovascular risk. A Show 2 more Physical activity: As per VA 2020 guidelines, advise practicing regular aerobic physical activity of any intensity and duration for primary and secondary prevention of CVD. B As per CCS 2016 guidelines, advise engaging in at least 150 minutes of moderate- to vigorous-intensity aerobic physical activity per week, in bouts of 10 minutes or more, in order to reduce the risk of CVD in adult patients. A Smoking cessation: advise abstaining from smoking in order to reduce the risk of CVD. A https://web.pathway.md/diseases/receTcWVpm18Q5oo1 7/19 6/29/23, 10:23 PM Dyslipidemia Pathway Omega-3 fatty acid supplements: As per CCS 2021 guidelines, do not use OTC omega-3 PUFA supplements to reduce CVD risk. D As per VA 2020 guidelines, avoid using omega-3 fatty acids dietary supplements to reduce CVD risk for primary or secondary prevention. D Other supplements: As per VA 2020 guidelines, insufficient evidence to recommend for or against the use of fiber, garlic, ginger, green tea, and red yeast rice supplements to reduce cardiovascular risks. I As per CCS 2016 guidelines, avoid prescribing vitamins, minerals, or supplements to prevent statin-associated myalgias. D 6. Specific circumstances Female patients: As per CCS 2021 guidelines, obtain screening with a complete lipid panel in the late postpartum period in female patients with a pregnancy complication such as the following as they have a higher risk of premature CVD and stroke with onset 10-15 years after index delivery: hypertensive disorders of pregnancy gestational diabetes preterm birth stillbirth low birth weight infant placental abruption. B Show 2 more As per ES 2020 guidelines, initiate statin therapy rather than hormone therapy for the treatment of dyslipidemia in postmenopausal patients. B Show 2 more As per ESC 2020 guidelines, do not use statins in premenopausal patients with diabetes mellitus planning pregnancy or not using adequate contraception. D As per AHA 2019 guidelines, take into account conditions specific to female patients, such as premature menopause and history of pregnancy-associated disorders such as hypertension, preeclampsia, gestational diabetes mellitus, small-for-gestational-age infants, and preterm deliveries, when discussing lifestyle intervention and the potential for benefit of statin therapy. B Show 2 more Elderly patients: As per ESC 2020 guidelines, initiate statin therapy for primary prevention, according to the level of risk, in older patients > 65 and 75 years old. A Show 3 more As per AHA 2019 guidelines, consider initiating a moderate-intensity statin in 75 years old patients with a LDL cholesterol level of 70-189 mg/dL. C https://web.pathway.md/diseases/receTcWVpm18Q5oo1 8/19 6/29/23, 10:23 PM Dyslipidemia Pathway Show 2 more Pediatric patients, screening: As per CPCA/CCS 2022 guidelines, obtain universal lipid screening (fasting or nonfasting, non-HDL cholesterol or LDL cholesterol) within the first decade of life (after 2 years old), coupled with cascade screening for identified cases of probable/definite familial hypercholesterolemia or other monogenic lipid disorders. Consider obtaining selective screening at any time in pediatric patients with identified cardiovascular risk factors or risk conditions or a positive family history of premature CVD or dyslipidemia. E As per PCNA/ASPC/APhA/AGS/ADA/ACPM/ABC/AAPA/ACC/AHA 2019 guidelines, consider obtaining fasting lipid profile or nonfasting non-HDL cholesterol once between the ages of 9 and 11 years, and again between the ages of 17 and 21 years, to detect moderate-to-severe lipid abnormalities in pediatric and adolescent patients without cardiovascular risk factors or family history of early CVD. C Show 3 more As per USPSTF 2016 guidelines, insufficient evidence to assess the risks and benefits of screening for lipid disorders in pediatric and adolescent individuals (< 20 years old). I Pediatric patients (clinical assessment): elicit a thorough history and perform a physical examination, with additional investigations obtained as needed, to exclude secondary causes of pediatric dyslipidemia. E Pediatric patients, genetic testing: As per CPCA/CCS 2022 guidelines, consider obtaining genetic testing, when accessible, to achieve definitive diagnoses of familial hypercholesterolemia or other genetic dyslipidemias. Consider establishing clinical diagnosis independent of genetic testing using available non- genetic criteria. E As per EAS/ESC 2020 guidelines, obtain testing for familial hypercholesterolemia in pediatric patients from the age of 5, or earlier if homozygous familial hypercholesterolemia is suspected. B Pediatric patients, lifestyle modifications: As per CPCA/CCS 2022 guidelines, offer lifestyle and dietary management as the first-line treatment strategy in nearly all patients with pediatric dyslipidemia. Continue lifestyle and dietary management if lipid-lowering medications are started. E As per EAS/ESC 2020 guidelines, educate pediatric patients with familial hypercholesterolemia to adopt a proper diet. B As per PCNA/ASPC/APhA/AGS/ADA/ACPM/ABC/AAPA/ACC/AHA 2019 guidelines: Counsel on lifestyle modifications for lowering LDL cholesterol in pediatric and adolescent patients with lipid abnormalities. B Advise intensifying lifestyle modifications, including moderate caloric restriction and regular aerobic physical activity, in pediatric and adolescent patients with lipid disorders related to obesity. A Pediatric patients, statin therapy: As per CPCA/CCS 2022 guidelines: Decide on the need for pharmacotherapy based on the average of results from at least 2 fasting lipid profiles obtained at least 2 weeks but no more than 3 months apart. E https://web.pathway.md/diseases/receTcWVpm18Q5oo1 9/19 6/29/23, 10:23 PM Dyslipidemia Pathway Consider initiating statin therapy beginning at age 8-12 years when LDL cholesterol remains above specific treatment thresholds despite lifestyle management. E As per EAS/ESC 2020 guidelines, initiate statin therapy in pediatric patients with familial hypercholesterolemia from 8-10 years of age. B As per PCNA/ASPC/APhA/AGS/ADA/ACPM/ABC/AAPA/ACC/AHA 2019 guidelines, consider initiating statin therapy in > 10 years old pediatric and adolescent patients with LDL cholesterol level persistently 190 mg/dL ( 4.9 mmol/L) or 160 mg/dL ( 4.1 mmol/L) with a clinical presentation consistent with familial hypercholesterolemia not responding adequately to 3-6 months of lifestyle therapy. C Pediatric patients (management of hypertriglyceridemia): consider initiating pharmacotherapy in addition to strict dietary management, including omega-3 fatty acids or fibrates, and offering evaluation and management by a lipid specialist in patients with persistent hypertriglyceridemia (2.3-5.5 mmol/L) despite lifestyle interventions or severe (> 5.5 mmol/L) hypertriglyceridemia at diagnosis. E Pediatric patients, treatment targets: As per CPCA/CCS 2022 guidelines, incorporate routine safety monitoring (for hepatic toxicity and myopathy) and LDL cholesterol treatment targets with statin therapy: low-risk conditions: LDL cholesterol < 2.6 mmol/L high-risk conditions: LDL cholesterol < 3.4 mmol/L or 50% reduction. E As per EAS/ESC 2020 guidelines, target LDL cholesterol level of < 135 mg/dL (< 3.5 mmol/L) in > 10 years old pediatric patients with familial hypercholesterolemia. B Pediatric patients (indications for referral): consider referring patients to a pediatric lipid specialist to facilitate lifestyle or pharmacotherapy management or if there is marked dyslipidemia at diagnosis (LDL cholesterol 4.1 mmol/L or triglyceride levels 5.5 mmol/L) or dyslipidemia in the setting of risk factors or at-risk conditions. E Patients with obesity: assess components of the metabolic syndrome and body fat distribution to accurately determine the level of CVD risk in patients with obesity. E Show 4 more Patients with severe hypercholesterolemia: initiate maximally tolerated statin therapy in 20- 75 years old patients with LDL cholesterol level of 190 mg/dL ( 4.9 mmol/L). B Show 5 more Patients with hypertriglyceridemia: As per ES 2020 guidelines, initiate pharmacologic treatment as adjunct to dietary modifications and exercise to prevent pancreatitis in adult patients with fasting triglyceride levels > 500 mg/dL (5.6 mmol/L). B Show 4 more As per ESC 2020 guidelines, initiate statins as first-line therapy to reduce cardiovascular risk in high risk patients with hypertriglyceridemia (triglyceride levels > 200 mg/dL or > 2.3 mmol/L). B Show 3 more As per AHA 2019 guidelines, address and treat lifestyle factors (such as obesity and metabolic syndrome), secondary factors (such as diabetes mellitus, chronic liver or kidney https://web.pathway.md/diseases/receTcWVpm18Q5oo1 10/19 6/29/23, 10:23 PM Dyslipidemia Pathway disease and/or nephrotic syndrome, hypothyroidism), and medications that increase triglycerides in 20 years old adult patients with moderate hypertriglyceridemia (fasting or nonfasting triglycerides 175-499 mg/dL or 2.0-5.6 mmol/L). B Show 3 more Patients with familial hypercholesterolemia, screening: As per EAS/ESC 2020 guidelines, obtain family screening for familial hypercholesterolemia once the index case is diagnosed. B As per CCS 2018 guidelines: Implement cascade screening (lipid profile) protocols at the local, provincial and national level and offer in first-degree relatives of patients with familial hypercholesterolemia. B Consider obtaining universal cholesterol level screening for the detection of familial hypercholesterolemia in children with reverse cascade screening of parents when warranted. C Patients with familial hypercholesterolemia, diagnosis: As per EAS/ESC 2020 guidelines, suspect the diagnosis of familial hypercholesterolemia in patients with: premature coronary artery disease (males < 55 years old; females < 60 years old) severely elevated LDL cholesterol in adults (> 190 mg/dL or > 5 mmol/L) and in pediatrics (> 150 mg/dL or > 4 mmol/L) relatives having premature fatal or non-fatal CVD relatives having tendon xanthomas. B Show 2 more As per CCS 2018 guidelines: Define familial hypercholesterolemia using the Dutch Lipid Clinic Network Criteria, Simon Broome Registry or Familial Hypercholesterolemia Canada definition. A Offer genetic testing, when available, to complement a diagnosis of familial hypercholesterolemia and enable cascade screening. A Patients with familial hypercholesterolemia (CVD risk stratification): do not use current risk calculators (Framingham Risk Score, Pooled Cohort Equation, European SCORE) to determine cardiovascular risk in patients with familial hypercholesterolemia. D Show 2 more Patients with familial hypercholesterolemia, management: As per CCS 2021 guidelines: Initiate PCSK9 inhibitor (alirocumab or evolocumab) to lower LDL cholesterol level in patients with heterozygous familial hypercholesterolemia without clinical ASCVD, if LDL cholesterol remains above the target (LDL cholesterol 2.5 mmol/L or < 50% reduction from baseline or ApoB 0.85 mg/dL or non-HDL cholesterol 3.2 mmol/L) despite maximally tolerated statin therapy with or without ezetimibe therapy. A Initiate PCSK9 inhibitor (alirocumab or evolocumab) in patients with heterozygous familial hypercholesterolemia and ASCVD, if LDL cholesterol remains above the threshold 1.8 mmol/L (or ApoB 0.7 mg/dL or non-HDL cholesterol 2.4 mmol/L) despite maximally tolerated statin therapy with or without ezetimibe. A https://web.pathway.md/diseases/receTcWVpm18Q5oo1 11/19 6/29/23, 10:23 PM Dyslipidemia Pathway Updated evidence: FOURIER-OLE In patients with a history of established ASCVD and a fasting low-density lipoprotein cholesterol level 70 mg/dL while on statin, evolocumab was superior to placebo in parent study with respect to the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. Michelle L O'Donoghue et al. Circulation. 2022 Oct 11. As per EAS/ESC 2020 guidelines, treat patients with familial hypercholesterolemia and ASCVD or another major risk factor as very high risk patients, and patients without ASCVD or other risk factors as high risk patients. B Show 3 more As per PCNA/ASPC/APhA/AGS/ADA/ACPM/ABC/AAPA/ACC/AHA 2019 guidelines: Consider adding a PCSK9 inhibitor in 30-75 years old patients with heterozygous familial hypercholesterolemia and LDL cholesterol level of 100 mg/dL ( 2.6 mmol/L) with maximally tolerated statin and ezetimibe therapy. C Insufficient evidence to support addition of a PCSK9 inhibitor in patients with familial hypercholesterolemia without evidence of clinical ASCVD receiving maximally tolerated statin and ezetimibe therapy. I As per CCS 2018 guidelines, consider advising a healthy lifestyle in patients with familial hypercholesterolemia. C Show 8 more As per CCS 2016 guidelines, consider initiating lomitapide and mipomersen exclusively in patients with homozygous familial hypercholesterolemia. C Patients with familial hypercholesterolemia (homozygous FH): refer patients with homozygous familial hypercholesterolemia to a specialized lipid clinic. Obtain complete evaluation for genetic analysis, presence of ASCVD and initiate aggressive lipid-lowering therapies including consideration for extracorporeal LDL cholesterol removal, lomitapide and PCSK9 inhibitors. B Patients with ASCVD, general indications: As per EAS/ESC 2020 guidelines, consider targeting LDL cholesterol level of < 40 mg/dL (< 1.0 mmol/L) in patients with ASCVD experiencing a second vascular event within 2 years (not necessarily of the same type as the first event) while taking maximally tolerated statin- based therapy. C As per PCNA/ASPC/APhA/AGS/ADA/ACPM/ABC/AAPA/ACC/AHA 2019 guidelines, initiate or continue high-intensity statin therapy with the aim of achieving a 50% reduction in LDL cholesterol levels in 75 years old patients with clinical ASCVD. A Show 8 more Patients with ASCVD: as per ACS 2020 guidelines, initiate or continue high-dose statins as early as possible in all patients with acute coronary syndrome without any contraindication or definite history of intolerance, regardless of initial LDL cholesterol levels. A Show 6 more https://web.pathway.md/diseases/receTcWVpm18Q5oo1 12/19 6/29/23, 10:23 PM Dyslipidemia Pathway Patients with ASCVD (ischemic stroke): initiate intensive LDL cholesterol-lowering therapy in patients with a history of ischemic stroke or TIA, particularly recurrent ischemic stroke, as they are at very high risk of ASCVD. A Patients with ASCVD (PAD): initiate lipid-lowering therapy in patients with peripheral arterial disease, including a maximum tolerated dose of statins, plus ezetimibe or a combination with PCSK9, if needed, to reduce the risk of ASCVD events. A Patients with aortic valvular disease: do not initiate lipid-lowering therapy in patients with aortic valvular stenosis without coronary artery disease to slow progression of aortic valve stenosis in the absence of other indications for its use. D Patients with heart failure: As per ACC 2022 guidelines, initiate statins to prevent symptomatic HF and adverse cardiovascular events in patients with a recent or remote history of myocardial infarction or acute coronary syndrome. A As per ESC 2021 guidelines, initiate statins in patients at high risk of CVD or with CVD to prevent or delay the onset of HF and to prevent HF hospitalizations. A As per ESC 2020 guidelines, do not initiate lipid-lowering therapy in patients with HF in the absence of other indications for its use. D As per AHA 2019 guidelines, consider initiating moderate-intensity statin therapy to reduce the occurrence of ASCVD events in patients with HFrEF attributable to ischemic heart disease having a reasonable life expectancy of 3-5 years and not being already on a statin because of ASCVD. C Patients with diabetes mellitus: As per ADA 2023 guidelines, advise lifestyle modifications focusing on weight loss (if indicated), following a Mediterranean style or DASH eating pattern, reducing consumption of saturated fat and trans fat, increasing dietary omega-3 fatty acids, viscous fiber, and plant stanols/sterols intake, and increasing physical activity to improve the lipid profile and reduce the risk of developing ASCVD in patients with diabetes. A Show 15 more As per ES 2020 guidelines, initiate statin therapy in addition to lifestyle modification to reduce cardiovascular risks in adult patients with T2DM and other cardiovascular risk factors. A Show 8 more As per ESC 2020 guidelines, target LDL cholesterol reduction of 50% from baseline and the following LDL cholesterol levels in patients with with T2DM: < 55 mg/dL (< 1.4 mmol/L) in very high risk patients < 70 mg/dL (< 1.8 mmol/L) in high risk patients. A Show 4 more As per AHA 2019 guidelines, initiate moderate-intensity statin therapy in 40-75 years old patients with diabetes mellitus, regardless of estimated 10-year ASCVD risk. A Show 6 more Patients with chronic kidney disease, management: As per EAS/ESC 2020 guidelines, view patients with KDOQI stage 3-5 CKD as high or very high risk patients for ASCVD. A https://web.pathway.md/diseases/receTcWVpm18Q5oo1 13/19 6/29/23, 10:23 PM Dyslipidemia Pathway Show 2 more As per PCNA/ASPC/APhA/AGS/ADA/ACPM/ABC/AAPA/ACC/AHA 2019 guidelines, consider initiating a moderate-intensity statin or moderate-intensity statins combined with ezetimibe in 40-75 years old patients with LDL cholesterol 70-189 mg/dL, a 10-year ASCVD risk of 7.5% and CKD not treated with dialysis or kidney transplantation. C Landmark trials: SHARP In patients with advanced CKD, simvastatin plus ezetimibe was superior to placebo with respect to major atherosclerotic events. Baigent C et al. Lancet. 2011 Jun 25. As per CCS 2016 guidelines, offer statins or a statin/ezetimibe combination to reduce CVD events in 50 years old patients with CKD not treated with dialysis or a kidney transplant. A Landmark trials: SHARP In patients with advanced CKD, simvastatin plus ezetimibe was superior to placebo with respect to major atherosclerotic events. Baigent C et al. Lancet. 2011 Jun 25. Patients on hemodialysis: As per ESC 2020 guidelines, consider continuing statins, ezetimibe or a statin/ezetimibe combination in patients already using these medications at the time of dialysis initiation, particularly in patients with ASCVD. C As per AHA 2019 guidelines: Consider continuing statin therapy in adult patients with CKD initiating dialysis and already receiving statin therapy. C Avoid initiating statin therapy in adult patients with advanced kidney disease requiring dialysis treatment. D Landmark trials: AURORA In patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis, rosuvastatin was not superior to placebo with respect to death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke (events per 100 patient-years). Fellstrom BC et al. N Engl J Med. 2009 Apr 2. As per CCS 2016 guidelines: Consider continuing lipid-lowering therapy in adult patients with dialysis-dependent CKD already receiving it at the time of dialysis initiation. C https://web.pathway.md/diseases/receTcWVpm18Q5oo1 14/19 6/29/23, 10:23 PM Dyslipidemia Pathway Consider avoiding lipid-lowering therapy in adult patients with dialysis-dependent CKD. D Landmark trials: AURORA In patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis, rosuvastatin was not superior to placebo with respect to death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke (events per 100 patient-years). Fellstrom BC et al. N Engl J Med. 2009 Apr 2. Patients with inflammatory diseases and HIV: initiate moderate-intensity statin therapy or high-intensity statin therapy in 40-75 years old patients with LDL cholesterol levels 70-189 mg/dL, a 10-year ASCVD risk 7.5% and chronic inflammatory disorders or human immunodeficiency virus. B Show 2 more Patients with solid organ transplants: consider initiating statins as first-line therapy in patients with solid organ transplants. Initiate statins at low doses with carefully titrating upwards and with caution regarding potential drug-drug interactions, particularly for patients receiving ciclosporin. C Show 2 more Patients with endocrine disorders (evaluation): obtain a lipid panel for the assessment of triglyceride levels and for calculating LDL cholesterol in adult patients with endocrine disorders. B Show 3 more Patients with endocrine disorders (thyroid disease): avoid treating hyperlipidemia until the patient becomes euthyroid in order to more accurately assess the lipid profile in patients with overt hypothyroidism. D Show 2 more Patients with endocrine disorders (Cushing's syndrome): obtain cardiovascular risk assessment and initiate treatment in adult patients with cured Cushing's syndrome as in the general population. E Show 3 more Patients with endocrine disorders (adult growth hormone deficiency): assess lipid profile at diagnosis to screen for dyslipidemia in adult patients with GH deficiency. B Show 2 more Patients with endocrine disorders (acromegaly): consider obtaining usual lipid profile before and after treatment of GH excess in adult patients with acromegaly. C Patients with endocrine disorders (PCOS): Obtain a fasting lipid panel at diagnosis to assess cardiovascular risk in patients with PCOS. B Avoid using lipid-lowering therapies for the treatment of hyperandrogenism or infertility in patients with PCOS. D https://web.pathway.md/diseases/receTcWVpm18Q5oo1 15/19 6/29/23, 10:23 PM Dyslipidemia Pathway Patients with endocrine disorders (testosterone deficiency): consider initiating testosterone therapy as symptomatically indicated and not as an approach to improve dyslipidemia or CVD risk in patients with low testosterone levels. C 7. Patient education Shared decision-making: As per AHA 2019 guidelines, promote shared decision-making when initiating lipid-lowering therapy, and discuss the potential benefits and adverse effects of treatments, as well as the potential for drug-drug interactions. B Show 2 more As per CCS 2016 guidelines, share the results of cardiovascular risk assessment with the patient to support shared decision-making and improve the likelihood of reaching lipid targets. A 8. Follow-up and surveillance Monitoring for adherence to treatment: As per VA 2020 guidelines, consider offering intensified patient care (such as phone calls, emails, patient education, drug regimen simplification) to improve adherence to lipid-lowering medications. C As per AHA 2019 guidelines, assess adherence to changes in lifestyle and effects of LDL cholesterol-lowering medication by measurement of fasting lipids and appropriate safety indicators 4-12 weeks after statin initiation or dose adjustment and every 3-12 months thereafter based on need to assess adherence or safety. A Monitoring for adverse effects of statins: As per AHA 2019 guidelines, conduct a clinician-patient risk discussion before initiation of statin therapy to review net clinical benefit, weighing the potential for ASCVD risk reduction against the potential for statin-associated side effects, statin-drug interactions, and safety, while emphasizing that side effects can be addressed successfully. A Show 8 more As per CCS 2016 guidelines, evaluate all purported statin-associated symptoms systematically incorporating observation during cessation and reinitiation of statins (same or different statin, same or decreased potency, same or decreased frequency of dosing) to identify a tolerated, statin-based therapy for chronic use. B Clinical findings Symptoms Past medical history Ankle swelling Cushing's syndrome Chest pain Diabetes mellitus Difficulty breathing Genetic abnormality https://web.pathway.md/diseases/receTcWVpm18Q5oo1 16/19 6/29/23, 10:23 PM Dyslipidemia Pathway Fainting Human immunodeficiency virus infection Fatigue Hypercholesterolemia Heartburn Hypothyroidism Leg pain IBD Nausea Metabolic disorders Palpitations Obesity Sweats PCOS Swelling Social history Family history Alcohol consumption Genetic predispositions Lab findings serum LDL serum cholesterol serum triglycerides Studies 2023 RACING In adult patients with diabetes mellitus and ASCVD, moderate-intensity statin plus ezetimibe combination therapy was not superior to high-intensity statin monotherapy with respect to the composite of cardiovascular death, major cardiovascular events, or nonfatal stroke at 3 years.