Anti-Lipemics II — Clinical Reasoning (25 High-Yield Questions)

LIP-001 • Question 1

A 52-year-old with LDL 210 mg/dL (no ASCVD yet) asks why the first-line therapy is a high-intensity statin. Which change best explains the LDL-lowering effect that drives outcome benefit?

Decreased chylomicron production from the intestine Increased hepatic LDL receptor expression and LDL clearance Inhibition of PCSK9 release from platelets Increased HDL synthesis in the liver Direct dissolution of atherosclerotic plaque

LIP-002 • Question 2

A patient on atorvastatin develops myalgias after starting clarithromycin. The mechanism for this adverse effect is best explained by:

Induction of CYP3A4 causing subtherapeutic statin levels Inhibition of CYP3A4 increasing statin exposure Inhibition of renal tubular secretion of statins Activation of PPAR-α increasing statin metabolism Chelation of statin in the gut

LIP-003 • Question 3

A 38-year-old with familial hypercholesterolemia is on maximally tolerated statin + ezetimibe but LDL remains 160 mg/dL. Which add-on most directly increases LDL receptor recycling?

Fenofibrate Alirocumab Niacin Colesevelam Icosapent ethyl

LIP-004 • Question 4

A 64-year-old with TG 980 mg/dL presents with epigastric pain and lipase elevation. After acute management, which long-term lipid strategy is the priority to prevent recurrence?

High-intensity statin alone Ezetimibe monotherapy Fibrate therapy and strict lifestyle (plus consider omega-3) to reduce TG PCSK9 inhibitor therapy Bile acid sequestrant therapy

LIP-005 • Question 5

A patient with LDL 165 mg/dL and TG 380 mg/dL asks what to treat first. The best next step is:

Fibrate first, then consider statin later Omega-3 first, then consider statin later Treat LDL first with statin-based therapy, then reassess TG Niacin first to raise HDL Bile acid resin first because it lowers TG

LIP-006 • Question 6

A patient wants to stop their statin because “HDL is what matters.” Which statement best reflects outcome evidence?

Raising HDL pharmacologically consistently reduces ASCVD events Lowering LDL reduces ASCVD events; HDL is a marker but not a reliable drug target Only triglyceride lowering improves outcomes LDL reduction helps only in diabetics Statins work mainly by raising HDL

LIP-007 • Question 7

Which lipid drug is least appropriate if triglycerides are 420 mg/dL due to its tendency to increase triglycerides?

Ezetimibe Bile acid sequestrant (e.g., colesevelam) Statin Fenofibrate Icosapent ethyl

LIP-008 • Question 8

A patient on niacin complains of intense flushing. Which pre-treatment can reduce this symptom and why?

Acetaminophen; blocks leukotrienes Aspirin; blocks prostaglandin-mediated vasodilation Diphenhydramine; blocks histamine release Prednisone; blocks NF-κB Metoprolol; blocks reflex tachycardia

LIP-009 • Question 9

A patient with LDL 145 mg/dL cannot tolerate any statin due to recurrent objective CK elevations. Which option is most reasonable next to lower LDL modestly with minimal systemic exposure?

Colesevelam Verapamil Furosemide Metformin Clonidine

LIP-010 • Question 10

Ezetimibe lowers LDL by blocking cholesterol uptake at the intestinal brush border via inhibition of:

HMG-CoA reductase NPC1L1 transporter PCSK9 enzyme PPAR-α receptor CETP transporter

LIP-011 • Question 11

Which scenario most strongly supports adding a PCSK9 inhibitor after statin therapy?

LDL 120 mg/dL after moderate-intensity statin in a low-risk patient LDL remains above goal despite high-intensity statin + ezetimibe in very-high-risk ASCVD HDL is low despite statin Triglycerides are 280 mg/dL Isolated low HDL with normal LDL

LIP-012 • Question 12

A patient with severe CKD asks if fenofibrate is safe. The major concern is:

Severe bradycardia Worsening creatinine/renal effects and dosing limitations Profound hypokalemia Angioedema Thyroid storm

LIP-013 • Question 13

A patient on high-intensity statin still has TG 220 mg/dL and established ASCVD. Which omega-3 product has evidence for ASCVD risk reduction in this setting?

Low-dose OTC fish oil Icosapent ethyl (EPA-only) DHA-only supplement Vitamin E Krill oil

LIP-014 • Question 14

A patient develops gallstones after starting a triglyceride-lowering medication. Which drug class is most associated with this adverse effect and why?

Statins; increase bile secretion Fibrates; increase cholesterol excretion into bile Ezetimibe; causes bile sludge PCSK9 inhibitors; crystallize bile acids Niacin; increases bilirubin conjugation

LIP-015 • Question 15

Which lipid parameter is most directly lowered by fibrates via PPAR-α activation and increased lipoprotein lipase activity?

LDL Triglycerides Lipoprotein(a) ApoB Total cholesterol only

LIP-016 • Question 16

A patient with LDL 190 mg/dL is planning pregnancy. Which statement is most appropriate?

Continue statin—benefits outweigh risks Stop statin; consider bile acid sequestrant if needed Switch to ezetimibe—safe in pregnancy Switch to PCSK9 inhibitor—safe in pregnancy Switch to niacin—safe in pregnancy

LIP-017 • Question 17

A patient with fatigue and right upper quadrant discomfort on statin therapy: which lab test best evaluates a known statin adverse effect?

Serum amylase AST/ALT TSH Troponin BNP

LIP-018 • Question 18

Which statement best explains why higher-intensity statins produce greater ASCVD benefit?

They raise HDL more They lower LDL more, and LDL lowering is causally linked to event reduction They prevent platelet activation directly They prevent atrial fibrillation They only work in smokers

LIP-019 • Question 19

A patient with diabetes is concerned about 'new-onset diabetes risk' from statins. Best counseling:

Statins frequently cause severe hypoglycemia Statins slightly increase diabetes risk, but ASCVD benefit usually outweighs this risk Statins should never be used in diabetes Only ezetimibe is safe in diabetes PCSK9 inhibitors worsen glucose more than statins

LIP-020 • Question 20

A patient with TG 650 mg/dL and heavy alcohol use asks what change matters most. Best recommendation:

Increase saturated fat intake Stop alcohol and reduce simple carbs/added sugars Start bile acid sequestrant Start niacin only Avoid exercise

LIP-021 • Question 21

A patient on gemfibrozil is started on a statin for LDL control. Why is this combination used cautiously?

It causes severe cough It increases risk of myopathy/rhabdomyolysis, especially with gemfibrozil It causes severe hypokalemia It causes torsades de pointes It is always safe

LIP-022 • Question 22

A patient’s lipid panel shows: LDL 80, HDL 38, TG 190. They ask for a drug “to raise HDL.” Best next step:

Niacin to raise HDL as primary goal No drug solely to raise HDL; treat based on ASCVD risk and LDL/TG priorities, emphasize lifestyle PCSK9 inhibitor to raise HDL Bile acid sequestrant to raise HDL Fibrate to raise HDL

LIP-023 • Question 23

A patient with very-high-risk ASCVD is on maximal statin + ezetimibe. LDL is still 85 mg/dL. Which therapy provides large additional LDL reduction via monoclonal antibody mechanism?

Evolocumab Gemfibrozil Niacin Colesevelam Icosapent ethyl

LIP-024 • Question 24

Which statement best fits modern atherosclerosis biology?

Plaques are sterile fat only; inflammation is irrelevant LDL retention triggers immune activation; inflammation drives plaque progression and rupture risk Only infections cause plaques HDL causes plaque rupture Triglycerides directly calcify arteries

LIP-025 • Question 25

A patient with triglycerides 410 mg/dL and constipation wants an LDL-lowering drug that works in the gut. Which option is most likely to worsen both issues?

Ezetimibe Bile acid sequestrant (colesevelam/cholestyramine) PCSK9 inhibitor Atorvastatin Icosapent ethyl