Hypercholesterolemia/Dyslipidemia II – Flashcards

Demonstrate working knowledge of how to apply the guidelines regarding the use, monitoring, and selection of optimal drug therapy for the management of a patient with dyslipidemia Demonstrate an understanding of basis for and evidence supporting the contemporary (ACC/AHA 2013) guideline for the risk reduction and prevention of ASCVD

There are 4 main statin benefit groups a) With Clinical ASCVD b) Primary elevations of LDL greater than or equal to 190 mg/dL c) Diabetes aged 40 to 75 with LDL of 70 to 189 mg/dL d) Without clinical ASCVD or diabetes with LDL cholesterol of 70 to 189 mg/dL and a 10 year ASCVD risk of greater than or equal to 7.5%

ACS Hx of MI Stable or Unstable Angina Coronary or other arterial revascularization Stroke TIA Peripheral Artery Disease (PAD)

1) No longer treat to target LDL (or non-HDL) values based on risk for either primary or secondary prevention 2) Employ high to moderate (or low) intensity statins 3) Empoly Pooled Cohort Equation for 10 year estimation of ASCVD risk---Key value is 7.5% 4) Age range for clear indications of moderate to high intensity statins appears to be 40 to 75 yo

1) Primary Prevention: greater than or equal to 21 yo with LDL of greater than 190 mg/dL = no need for 10 year assessment, use high intensity statins unless contraindicated 2) Primary Prevention for diabetes patients 40 to 75 yo = high intensity statins if risk is greater than or equal to 7.5% Discuss: Clinician & Patient engage in discussion considering potential ASCVD risk reduction benefits, adverse effects, drug-drug interactions, patient preferences before treatment recommendations Adverse effects include excess cases of new onset diabetes (0.3 excess cases per 100 treated for 1 year), rare cases of myopathy (0.01 excess cases per 100) and hemorrhagic stroke (0.01 excess cases per 100) Expert Panel emphasizes that the occurrence of a major CVD event (MI or stroke) represents a much greater harm to health status than does an increase in blood glucose leading to diagnosis of diabetes

Individuals with: LDL greater than or equal to 190 mg/dL Triglycerides greater than or equal to 500 mg/dL Non-HDL greater than 220 mg/dL Assessment approach for secondary cause: Fasting lipid panel Drug and disease reviews Family history studies Genetic testing for familial hyperlipidemia (FH)

Support the use of initial fasting lipid panel A second lipid panel 4 to 12 weeks after initiation of statin therapy to determine a patient's adherence Thereafter, assessments should be performed every 3 to 12 months as clinically indicated

1) Moderate intensity statin therapy should be used in individuals in whom high-intensity statin therapy would otherwise be recommended when characteristics predisposing them to statin-associated adverse effects are present Characteristics predisposing individuals to statin adverse effects include, but are not limited to: a) Multiple or serious comorbidities, including impaired renal or hepatic function b) History of previous statin intolerance or muscle disorders c) Unexplained ALT elevations greater than 3 times upper limit of normal d) Patient characteristics or concomitant use of drugs affecting statin metabolism e) Greater than 75 yo Additional Characteristics that may modify the decision to use higher statin intensities: a) History of hemorrhagic stroke b) Asian ancestry = CYP2C19 poor metabolizers = lower dose 2) Creatinine Kinase (CK) should not be routinely measured in individuals receiving statin therapy Baseline creatinine kinase (CK) is reasonable for individuals believed to be at increased risk for adverse muscle events based on a family history of statin intolerance or muscle disease, clinical presentation, or concomitant drug therapy that may increase the risk for myopathy During statin therapy, it is reasonable to measure creatinine kinase in individuals with severe muscle symptoms, including pain, tenderness, stiffness, cramping, weakness, or generalized fatigue 3) Baseline hepatic transaminase levels (ALT) should be performed before initiating statin therapy During statin therapy, it is reasonable to measure hepatic function if symptoms suggesting hepatotoxicity arise (ex: unusual fatigue or weakness, loss of appetite, abdominal pain, dark colored urine, or yellowing of the skin or sclera) 4) Individuals receiving statins should be evaluated for new onset diabetes according to current diabetes screening guidelines Those who develop diabetes during statin therapy should be encouraged to adhere to a heart healthy dietary pattern, engage in physical activity, achieve and maintain a healthy body weight, cease tobacco use, and continue statin therapy to reduce their risk of ASCVD events 5) For any dose of statins, it is reasonable to use caution if greater than 75 yo, or if taking meds that alter drug metabolism, taking multiple drugs, or taking drugs for conditions that require complex medication regimens (ex: drugs for organ transplant or HIV) 6) Reasonable to evaluate and treat muscle symptoms, including pain, tenderness, stiffness, cramping, weakness, or fatigue, in statin-treated patients as follows: a) To avoid unnecessary discontinuation of statins, obtain a history of prior or current muscle symptoms to establish a baseline before initiating statin therapy b) If unexplained severe muscle symptoms or fatigue develop during statin therapy, promptly d/c the statin and address the possibility of rhabdomyolysis by evaluating creatinine kinase, creatinine, and a urinalysis for myoglobinuria If mild to moderate muscle symptoms develop during statin therapy: a) D/C the statin until the symptoms can be evaluated b) Evaluate for conditions that might increase risk for muscle symptoms (ex: hypothyroidism, reduced renal or hepatic function, rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases) c) If muscle symptoms resolve, and if no contraindication exists, restart at original or lower dose of same statin to establsih a causal relationship d) If causal relationship exists, d/c original statin. Once muscle symptoms resolve, use a low dose of a different statin e) Once a low dose of a statin is tolerated, gradually incresae the dose as tolerated f) If, after 2 months without statin treatment, muscle symptoms or elevated CK levesl do not resolve completely, consider other causes g) If persistent muscle symptoms are determined to arise form a condition unrelated to statin therapy, or if predisposing condition has been treated, resume statin therapy at original dose

1) Baseline hepatic transaminases, fasting blood glucose or hemoglobin A1c, and uric acid should be obtained before initiating niacin, and again during up-titration to a maintenance dose and every 6 months thereafter 2) Niacin should not be used if: a) Hepatic transaminase elevations are higher than 2 to 3 times of upper limit of normal b) Persistent severe cutaneous symptoms, persistent hyperglycemia, acute gout or unexplained abdominal pain or GI symptoms occur c) New onset of atrial fibrillation or weight loss occurs Start Niacin at low dose and titrate to higher dose over a period of weeks as tolerated Take niacin with food or premedicate with aspirin 325 mg 30 minutes before niacin to alleviate flushing symptoms If extended release preparation is used, increase the dose of extended release niacin from 500 mg to max of 2000 mg/day over 4 to 8 weeks If immediate release niacin is chosen, start a dose of 100 mg three times dailiy and up titrate to 3000 mg/day, divided into 2 or 3 doses

1) Safety of Bile Acid Sequestrants Should not be used in individuals with baseline triglyceride levels of greater than or equal to 300 mg/dL or type III hyperlipoproteinemia because severe triglyceride elevations may occur 2) Safety of Cholesterol-Absorption Inhibitors It is reasonable to obtain baseline hepatic transaminases before initiating ezetimibe

1) Gemfibrozil should not be initiated in patients on statin therapy because of an increased risk for muscle symptoms and rhabdomyolysis 2) Fenofibrate may be considered concomitantly with low or moderate-intensity statin only if the benefits from ASCVD risk reduction or triglyceride lowering when triglycerides are greater than 500 mg/dL, are judged to outweigh the potential risk for adverse effects 3) Renal status should be evaluated before fenofibrate initiation, within 3 months after initiation, and every 6 months thereafter. Assess renal safety with both a serum creatinine level and eGFR based on creatinine a) If moderate or severe renal impairment, defined as eGFR less than 30 mL/min per 1.73 m^2 is present, fenofibrate should not be used b) If eGFR between 30 and 59 mL/min per 1.73 m^2, the dose of fenofibrate should not exceed 54 mg/day c) If, during follow up, the eGFR decreases persistently to less than or equal to 30 mL/min per 1.73 m^2, fenofibrate should be discontinued

AIM-HIGH and HPS2-THRIVE demonstrated the futility of adding niacin in individuals with low HDL, high triglycerides, and high risk patients, respectively ACCORD (with fenofibrate) demonstrated the futility of adding fenofibrate in persons with diabetes. However, subgroup analysis suggested that fenofibrate may reduce ASCVD events in patients with diabetes, high triglycerides, and low HDL, this is hypothesis generating and needs further testing in comparison to the evidence-based use of a high intensity statin

Familial Hypercholesterolemia with LDL of greater than or equal to 190 mg/dL = in many cases, individuals with familial hypercholesterolemia are unable to achieve an LDL goal of less than 100 mg/dL Patients or groups at higher baseline absolute risk, therefore, will derive greater absolute benefit from initiation of statin therapy over a period of 5 to 10 years Moderate intensity statin therapy should be initiated or continued for adults 40 to 75 yo with diabetes----if has ASCVD risk of greater than or equal to 7.5% = high intensity statin Adults 40 to 75 yo with LDL from 70 to 189 mg/dL, without ASCVD or diabetes and an estimated 10 year ASCVD risk of greater than or equal to 7.5% should be treated with moderate to high intensity statin therapy High intensity statin therapy should be initiated for continued first line therapy in women and men less than or equal to 75 yo who have clinical ASCVD, unless contraindicated In individuals with clinical ASCVD and greater than 75 yo: a) Evaluate the potential for ASCVD risk reduction benefits and risk for adverse effects, drug-drug interactions b) Consider patient preferences when initiating a statin c) Continue statin therapy in those who are tolerating it 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, a moderate intensity statin should be used as the second option if tolerated

Heart healthy lifestyle habits are the foundation of ASCVD prevention Treating to a lipid target is no longer target High intensity statin is your target in 4 benefit groups unless it is not appropriate to do so These guidelines are not a replacement for clinical judgement, they are meant to guide and inform decision making Discussion with patient and consideration of patient's preference are important aspect of statin pharmacotherapy

1) According to ACC/AHA 2013 Guidelines, how would you approach prevention of ASCVD for AM? c) Start rosuvastatin 20 mg daily = high intensity statin 2) Four weeks into statin therapy, AM presents with moderate muscle pain, which of the following represents the most defensible course of action c) D/C statin and obtain CK levels

According to ACC/AHA 2013 Guidelines, which of the following is the most defensible statement to treat PM's dyslipidemia? b) PM has LDL of greater than 190 mg/dL, ASCVD risk of greater than 7.5%, high intensity statin is warranted