Dyslipidemia Flashcards
What are the 4 groups that would benefit from Statin therapy?
-secondary prevention for pt with clinical ASCVD
-LDL= 190mg/dL +
-diabetes + age 40-75
-10 year ASCVD risk 7.5% + AND age 40-75
What is the LDL lowering affects of high intensity statin?
50%+
What is the LDL lowering affects of moderate intensity statin?
30-50%
What is the LDL lowering affects of low intensity statin?
<30%
What is a clinical ASCVD?
-acute coronary syndrome (MI, stable, and unstable angina)
-coronary or other arterial revascularization
-history of ischemic stroke or transient ischemic attack (TIA)
-peripheral artery disease
What are the high-risk conditions?
-age > 65yo
-genetics
-DM
-HTN
-CKD
-smoker
-persistently elevated LDL despite maximally tolerated statin +ezetimibe
-history of congestive heart failure
Which Statin would be best for secondary prevention of ASCVD?
high intensity statin, except if pt > 75 yo (possibly use moderate intensity)
When should lipid panel be monitored after Statin initiation or change?
4-12 weeks
What is goal LDL of very high risk secondary prevention pt?
<55 mg/dL
What is goal LDL of not very high risk secondary prevention pt?
< 70mg/dL
What primary prevention groups would benefit from a high intensity Statin?
-LDL= 190mg/dL +
-DM AND age 40-75yo
-ASCVD risk 20%+ AND age 40-75yo
What are DM specific risk factor enhancers?
-long duration of disease
-albuminuria
-eGFR < 60mL/min
-retinopathy
-neuropathy
-ABI < 0.9
What is the risk of severely elevated triglycerides in pt?
pancreatitis
What is the diagnosis criteria for persistent hypertriglyceridemia?
fasting TG 150mg/dL+ following 4-12 weeks of lifestyle intervention
What disease may cause hypertriglyceridemia?
-poorly controlled DM
-hypothyroidism
What diet/lifestyle choices may cause hypertriglyceridemia?
-excess alcohol
-diet high in saturated fat, sugar, high glycemic foods
-sedentary lifestyle
What drugs may cause hypertriglyceridemia ?
-propofol
-beta blockers
-glucocorticoids
-oral estrogens
-oncology treatment
-atypical antipsychotics
-immunosuppressants
What lifestyle interventions can be implemented for hypertriglyceridemia?
-reduce or eliminate added sugars
-total fat reduction
-weight loss
-decrease alcohol intake
-aerobic activity
-restriction of sugar/refined carbohydrates
What is the MOA of Statins?
HMG Co-A Reductase Inhibitor
What is the first-line treatment for LDL lower for ASCVD risk reduction?
Statin
What Statins are high intensity?
atorvastatin 40-80, rosuvastatin 20-40
What is the major enzyme for Atorvastatin?
CYP3A4
What is the major enzyme for Pravastatin?
no significant CYP metabolism
What is the major enzyme for Rosuvastatin?
CYP2C9
What is the major enzyme for Simvastatin?
CYP3A4
What Statin must be dosed at bedtime?
simvastatin
Which Statin is the most lipophilic?
simvastatin
What are the adverse effects of Statins?
-statin associated muscle symptoms (SAMS): myalgias, myopathies/rhabdomyolyis MOST COMMON CAUSE OF DISCONTINUATION
-newly diagnosed diabetes (more frequent with diabetes risk factors)
-liver transaminase elevation/hepatic failure
-cognitive impairment
What are the drug interactions of Statins?
-gemfibrozil
-bile acid sequestrants
-calcium channel blockers
-cyclosporine/tacrolimus
-amiodarone
What are the monitoring parameters of Statins?
-SAMS, at baseline and then 6-12 week after initiation (each follow-up visit)
-creatinine kinase (CK), possibly at baseline and if muscle symptoms develop
-ALT, AST, if indicated
-TSH, if symptoms develop
How can Statin induced myopathies be managed?
-decrease statin dose
-switch statin
-nondaily statin dosing
-utilize nonstatins
What are modifiable risk factors that increase the risk of statin intolerance?
-hypothyroidism
-drug interactions
-alcohol use
-strenuous exercise
-vitamin D deficiency
-obesity
-DM
What are the contraindications of Statins use?
-active or chronic liver disease
-breastfeeding
-drug interactions
-pregnancy (not complete contraindication, but strongly encouraged to stop statin use)
What is the indication for non-statin therapy?
-insufficient response to statin therapy
-intolerance to statin therapy
-severe hypertriglyceridemia
-ASCVD risk reduction: icosapent ethyl
What is the MOA of Ezetimibe?
inhibits NPC1L1 proteins to reduce cholesterol absorption in small intestine
What is the indication for Ezetimibe therapy?
additive LDL lowering therapy with statin (not to be used alone= no benefit)
What are the adverse effects of Ezetimibe?
typically well tolerated but may experience, diarrhea, hepatitis, pancreatitis
What are the precautions of Ezetimibe?
pregnancy/breastfeeding, moderate/severe hepatic disease
What is the MOA of PCSK9 inhibitor mAb?
binds PCSK9 and increases LDL receptors available to clear circulating LDL
What is the indication of PCSK9 inhibitors mAb?
combination therapy for high risk patients, statin intolerant patients, genetic dyslipidemia
What are the adverse effects of PCSK9 inhibitor mAb?
well tolerated but may experience muscle aches, urticaria, injection site reactions
What is the MOA of Inclisiran?
siRNA that targets PCSK9 messenger RNA to inhibit PCSK9 synthesis (similar to PSCK9 mAb inhibitor)
What are the adverse effects of Inclisiran?
injection site reaction, arthralgias
What is the indication of Bempedoic Acid?
adjunct to max tolerated statin for additional LDL lowering therapy
What are the adverse effects of Bempedoic Acid?
hyperuricemia/gout
What are the contraindications of Bempedoic Acid?
-pregnancy/breastfeeding
-pediatrics/severe renal impairment/dialysis = not studied
What is the MOA of Bile Acid Sequestrants(BAS)?
binds bile acid in Gi tract to prevent its reabsorption to encourage cholesterol to be synthesized to bile acid
What are the indications of Bile Acid Sequestrants?
-add on to statin therapy
-pregnancy
What are the adverse effects of Bile Acid Sequestrants?
constipation, heartburn, nausea, bloating
What are the contraindications of Bile Acid Sequestrants?
TG > 300 mg/dL
What are the adverse effects of Niacin?
-flushing (prostaglandin mediated)
-hyperglycemia
-hyperuricemia/gout
-GI upset
What is first line therapy for hypertriglyceridemia?
fibric acid derivatives
What drugs are fibric acid derivatives?
gemfibozil, fenofibrate, fenofibric acid
What is the effect of fibric acid derivatives on lipid profile?
decrease TG and increase HDL (little impact on LDL)
What are the adverse effects of Fibric Acid derivatives?
-dyspepsia
-N/V
-skin rash
-gallstones
-myopathy (especially in combo with statins)
What are the contraindications of Fibric Acid derivatives?
-moderate-severe renal impairment, eGFR <30 (renal adjustment needed if eGFR 30-59)
-hepatic disease
What is the indication of Omega-3-fatty acids/Icosapent ethyl?
adjunct for TG lowering therapy for pt with very high TG (>500mg/dL)
What are the adverse effects of Omega-3-ftty acids?
-dyspepsia
-nausea
-prolonged bleeding time (use caution in pt on blood thinners)
-AFib
-DHA can raise LDL, but EPA doesn’t (icosapent ethyl is EPA only)
