Lipid Lowering Drugs

Overview – Lipid Lowering Drugs

Lipid lowering drugs are a cornerstone in the management of hypercholesterolaemia and hyperlipidaemia, both of which are significant risk factors for atherosclerosis and cardiovascular disease. These medications work through various mechanisms to reduce low-density lipoprotein (LDL), triglycerides, and sometimes increase high-density lipoprotein (HDL). They are often initiated alongside or following lifestyle changes when patients are at elevated cardiovascular risk.

Definition

Lipid lowering drugs are a group of medications used to reduce serum lipid levels, particularly LDL cholesterol and triglycerides. They help prevent atherosclerotic cardiovascular diseases, including myocardial infarction and stroke.

Indications

• Primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD)
• Familial hypercholesterolaemia
• Hypertriglyceridaemia
• Mixed dyslipidaemia
• Acute coronary syndrome (as part of secondary prevention)

Classes of Lipid Lowering Drugs

1. Statins – HMG-CoA Reductase Inhibitors

Classical Agents:

• Simvastatin
• Fluvastatin
• Pravastatin
• Lovastatin

Note: These are fungal derivatives (Aspergillus), which can trigger immune-related adverse effects.

Mechanism of Action:

• Inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis (converts HMG-CoA → mevalonate)
• ↓ Endogenous cholesterol synthesis
• ↑ LDL-receptor expression in hepatocytes → ↑ LDL clearance from plasma
• Additional anti-inflammatory effects on arterial walls may reduce atherosclerotic risk

Side Effects:

• Myositis → ↑ Creatine Kinase
• Can progress to rhabdomyolysis
• Immune-related adverse effects due to fungal origin

2. Ion Exchange Resins – Bile Acid-Binding Resins

Classical Agents:

• Colestyramine
• Colestipol

Mechanism of Action:

• Bind bile acids and dietary cholesterol in the gut → prevent reabsorption
• Stimulate hepatic LDL receptor upregulation to compensate for bile loss → ↑ LDL clearance
• ↓ Total blood cholesterol

Side Effects:

• Malabsorption of fat-soluble vitamins (A, D, E, K) and folate
• Constipation – often requires concurrent laxatives

3. Ezetimibe

Mechanism of Action:

• Blocks cholesterol absorption at the brush border of the small intestine (specifically the duodenum)

Side Effects:

• Diarrhoea
• Abdominal pain
• Headache
• Avoid in lactating women (passes into breast milk)

Treating Hyperlipidaemia

4. Fibrates

Classical Agents:

• Clofibrate
• Gemfibrozil
• Fenofibrate
• Bezafibrate
• Ciprofibrate

Mechanism of Action:

• Activate PPAR-α →
  • ↑ transcription of lipoprotein lipase
  • ↑ conversion of VLDL to LDL
  • ↓ VLDL production
  • ↑ hepatic LDL uptake

Net effect: Marked ↓ in VLDL/triglycerides, modest ↓ LDL, and mild ↑ HDL

Side Effects:

• Myositis
• ↑ bile production → may cause gallstones
• Rare: Renal failure

5. Nicotinic Acid (Niacin) – Last-Resort Therapy

Mechanism of Action:

• ↓ Hepatic production of VLDL
• ↓ Conversion of VLDL to LDL

Side Effects:

• Requires very high doses, often poorly tolerated
• Causes flushing and palpitations → mitigated with co-administered aspirin
• Can impair liver function
• Alters glucose tolerance
• May trigger gout

Summary – Lipid Lowering Drugs

Lipid lowering drugs play a critical role in reducing cardiovascular risk through their effects on cholesterol and triglyceride levels. Statins remain first-line for most patients, while bile acid resins, ezetimibe, fibrates, and niacin provide additional or alternative mechanisms depending on lipid profile and tolerability. For a broader context, see our Pharmacology & Toxicology Overview page.