Lipid Lowering Medications

Pathogenesis of plaque growth and ASCVD risk

LDL enter arterial wall → Oxidized by free radial → MC engulf oxLDL → Foam cell

How does high Tg and chylomicron cause cellular necrosis and inflammation

Tg hydrolyzed by lipase → High FFA; chylomicron causes hyperviscosity → Pancreatic ischemia → cell death and inflammation

Intestinal target lipid lowering agents

Exetimibe, bile acid sequestrants

Liver targeted lipid lowering agents

Statins, PCSK9 inhibitors

Bloodstream targeted lipid lowering agents

Fibrates, niacin, omega 3 FFA

Statin mechanism of action

Inhibit HMG-CoA reductase → Lower cholesterol synthesis → Increased LDL clearance from blood

Statins ranked by intensity

Rosuvastatin (>=50% LDL reduce) > Atorvastatin (30-49% reduction) > simvastatin (<30% reduction)

SE of statin

Rhabdomyolysis, transaminitis, GI upset

Statin drug interactions

Macrolide, azole, grapefruit juice (increased myopathy risk)

What is ezetimibe

Inhibit NPC1L1 transporter → Block absorption of cholesterol → Upregulate LDLr → LDL reduction 15-20%

Ezetimibe use and side effect

Used with statin if LDL goal is not met or if statin cannot be used; SE = mild GI symptom and rare transaminitis

What are PCSK9 inhibitors

Increased LDL recycling into liver → 50-60% LDL reduction

What are fibrates

PPAR alpha receptor agonist → Increase LPL activity → Increased clearance of Tg rich particles, used in severe hyperTg to prevent acute pancreatitis

What is the caution of using fibrates

Fibrates + statin increase myopathy risk → Gemfibrozil > fenofibrate has higher risk

What are bile acid sequestrants

Bind bile acid in gut to inhibit enterohepatic circulation; used in pregnant women; SE = constipation, bloating, reduced drug absorption

What are niacin

Lower VLDL production; limited use; SE = flushing (common), hyperglycemia

What are omega 3 fatty acids

Reduced fatty acid synthesis → lower Tg; used in Pt with very high Tg

LDL >=190 mg/dl what drug should be given

Moderate intensity statin (atorvastatin)

LDL 100-190 mg/dl + Thai CV risk score >10% what drug should be given

Low to moderate intensity statin (simvastatin)

LDL 100-190 mg/dl + Thai CV risk score <10% what drug should be given

None; life style modification

Goal LDL in normal Pt

100 mg/dl

Goal LDL in Pt with 2+ risk factor (DM, overweight, smoking, HTN, family history of ACS, CKD, albuminuria)

70 mg/dl

Goal LDL in Pt with previous ACS

55 mg/dl

Tg >500 mg/dl what drug should be given

Fibrates

Pt that fibrates are not successful/cannot be given what drug should be given

EPA/DHA or pure EPA (omega 3 fatty acids)

Pt on moderate intensity statin develops diffuse muscle aches, what is your approach, what labs are useful, what alternative therapy should you use

Approach: Assess severity

Lab: Creatinine kinase → If very high should stop statin

Alternative therapy: Ezetimibe or PCSK9 inhibitors instead of statin to lower LDL

Pt with Tg 650 mg/dl and prior episode of acute pancreatitis, what medication is first line, what is its MOA, what are the side effects you are concerned about

Fibrates are first line; MOA: Activate PPAR-a to increase LPL activity and increase breakdown of Tg rich lipoprotein (lower VLDL and Tg); SE = GI symptoms

A patient with established ASCVD is already on a maximally tolerated high-intensity statin. LDL-C remains at 130 mg/dL. What else should you add and why, what might limit the first choice option

Use exetimibe or PCSK9 inhibitor to help lower LDL even more; use ezetimibe first since PCSK9 inhibitors are more expensive