Antilipemics
Antilipemics are drugs that reduce atherogenic lipoproteins — primarily LDL cholesterol — in order to reduce atherosclerotic cardiovascular disease (ASCVD).
This module focuses on:
• Drug mechanisms • LDL reduction potency • Outcome data • Adverse effects • Clinical selection strategies
In cardiovascular pharmacology, lipid drugs are long-term mortality drugs.
They do not relieve symptoms. They prevent events.
Drug Classes Overview
| Class | Primary Mechanism | LDL Reduction | Mortality Benefit |
|---|---|---|---|
| Statins | HMG-CoA reductase inhibition → ↑ LDL receptors | ↓↓ (30–60%) | Strong |
| Ezetimibe | ↓ Intestinal cholesterol absorption | ↓ (~15–20%) | Moderate (add-on) |
| PCSK9 Inhibitors | Prevent LDL receptor degradation | ↓↓↓ (50–60%) | Strong (high-risk pts) |
| Bempedoic Acid | ATP citrate lyase inhibition | ↓ (~15–20%) | Emerging |
| Fibrates | PPAR-α activation → ↓ TG | Minimal LDL effect | Limited |
| Omega-3 / Icosapent | ↓ VLDL production | TG lowering | Select benefit |
1. Statins – Foundation Therapy
Statins are first-line therapy for ASCVD prevention.
Mechanism: • Inhibit HMG-CoA reductase • Decrease hepatic cholesterol synthesis • Upregulate LDL receptors • Increase LDL clearance
Clinical effects: • ↓ MI • ↓ Stroke • ↓ Cardiovascular mortality
2. Cholesterol Absorption Inhibition
Ezetimibe
Mechanism: • Blocks NPC1L1 transporter in intestine • Reduces dietary and biliary cholesterol absorption
Used: • Add-on to statin • Statin intolerance
3. PCSK9 Inhibitors
Mechanism: • Monoclonal antibodies that prevent LDL receptor degradation • Dramatically increase LDL clearance
Used: • Secondary prevention • Familial hypercholesterolemia • Very high-risk patients
4. ATP Citrate Lyase Inhibition
Bempedoic Acid
Mechanism: • Inhibits cholesterol synthesis upstream of HMG-CoA reductase • Liver-selective activation
Used: • Statin intolerance • Add-on therapy
5. Triglyceride-Focused Therapy
Fibrates
Mechanism: • Activate PPAR-α • Increase lipoprotein lipase activity • Reduce triglycerides
Omega-3 Fatty Acids / Icosapent Ethyl
Mechanism: • Reduce hepatic VLDL production
Used: • Severe hypertriglyceridemia • Select ASCVD risk reduction
Clinical Strategy
Lipid therapy is risk-based.
Primary Prevention: • Statin intensity based on ASCVD risk
Secondary Prevention: • High-intensity statin • Add ezetimibe if LDL above goal • Consider PCSK9 for very high risk
This module teaches you to:
✔ Choose statin intensity ✔ Manage statin intolerance ✔ Add second-line therapy appropriately ✔ Understand LDL percent reductions ✔ Recognize major adverse effects
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