Chapter 11 · Module 5

Fibrates, Niacin, Bile Acid Sequestrants, and Omega-3 Fatty Acids

Visual summary — mechanisms, clinical roles, and what to use versus what to avoid

Drug Class Comparison — The Four Classes at a Glance

Feature	Fibrates	Niacin	Bile Acid Sequestrants	IPE Ethyl Ester
Mechanism	PPAR-alpha activation	Inhibits adipose lipolysis; reduces VLDL synthesis	Binds bile acids; interrupts enterohepatic recirculation	Reduces VLDL-TG; anti-inflammatory; plaque effects
Primary lipid effect	TG ↓ 20–50%; HDL ↑ 10–20%	HDL ↑ 15–35% (best of any drug); TG ↓ 20–40%; LDL ↓ 15–25%	LDL ↓ 15–25%; may raise TG	TG ↓ 20–30%; LDL neutral
CV outcomes	Negative on background statin	Negative on background statin	Pre-statin era evidence only	Proven (REDUCE-IT, 4 g/day)
Current role	Severe TG ≥500 mg/dL (pancreatitis)	Essentially none	Pregnancy; statin intolerance; pediatric FH	ASCVD/diabetes + TG 135–499 on statin
Key caution	Gemfibrozil raises statin levels; use fenofibrate	Flushing; diabetes; hepatotoxicity; gout	Drug absorption interactions; avoid TG >300	Atrial fibrillation risk; no OTC fish oil substitute

Clinical Role Summary — What to Use and What to Avoid

Use these agents

Defined Evidence-Based Roles

Icosapentaenoic acid ethyl ester 4 g/day: established atherosclerotic cardiovascular disease or diabetes with triglycerides 135–499 mg/dL on statin (Class IIa)
Fenofibrate: severe triglycerides ≥500 mg/dL for pancreatitis prevention
Colesevelam: pregnancy, statin-intolerant patients, pediatric familial hypercholesterolemia
Bempedoic acid: statin-intolerant patients needing oral low-density lipoprotein lowering (proven cardiovascular outcomes)

Avoid these agents

Agents to Avoid or Discontinue

Niacin: no cardiovascular benefit on statin, significant harms — discontinue in most patients
Gemfibrozil with statins: high rhabdomyolysis risk — always use fenofibrate instead
DHA-containing omega-3 products: not proven for cardiovascular benefit; do not substitute for prescription icosapentaenoic acid ethyl ester
Bile acid sequestrants when triglycerides >300 mg/dL: risk of worsening hypertriglyceridemia

Key Clinical Rules

Niacin

The best high-density lipoprotein-raising drug on paper, but abandoned in clinical practice. Two large outcomes trials on background statin showed no cardiovascular benefit and significant harm. Raising high-density lipoprotein cholesterol pharmacologically is not a therapeutic target.

Bile Acid Sequestrant Drug Interaction

All other oral medications must be taken at least 1 hour before or 4 to 6 hours after a bile acid sequestrant dose. Non-specific binding in the gut reduces absorption of warfarin, levothyroxine, digoxin, statins, and many other drugs.

Omega-3 Fatty Acids — Prescription Only for CV Benefit

Only icosapentaenoic acid ethyl ester at 4 grams per day has proven cardiovascular benefit. DHA-containing products (including all OTC fish oil supplements) have not demonstrated cardiovascular event reduction and should not be prescribed as substitutes.