Statins
What examiners watch for is whether you can pick a statin intensity from an ASCVD risk category rather than chasing an LDL number. Statins (atorvastatin, rosuvastatin, simvastatin, pravastatin) inhibit HMG-CoA reductase, lower LDL, and reduce cardiovascular events across primary and secondary prevention. The four ACC/AHA benefit groups are clinical ASCVD, LDL ≥190, diabetes age 40–75, and ASCVD 10-year risk ≥7.5%. High-intensity statins (atorvastatin 40–80, rosuvastatin 20–40) are first-line for clinical ASCVD and LDL ≥190. Side effects are myalgias (the most common cause of discontinuation), rare rhabdomyolysis, and a small transaminase bump that does not usually require stopping. Avoid simvastatin and lovastatin with strong CYP3A4 inhibitors, including grapefruit juice.
📖 Overview
HMG-CoA reductase inhibitors reduce hepatic cholesterol synthesis. First-line for primary and secondary ASCVD prevention, diabetic patients 40–75 yrs, and LDL ≥190 mg/dL. Atorvastatin and rosuvastatin are high-intensity; simvastatin moderate-intensity. Pleiotropic effects (plaque stabilization, anti-inflammatory) beyond LDL lowering.
⚙️ Mechanism of Action
Competitive inhibition of HMG-CoA reductase → ↓ hepatic cholesterol synthesis → ↑ LDL receptor expression → ↓ serum LDL.
💎 Board Pearls
- 🍊 GRAPEFRUIT INTERACTION (simvastatin and atorvastatin) via CYP3A4 — can triple levels and cause rhabdomyolysis.
- 💪 Myalgia (5–10%) common; rhabdomyolysis rare but serious → check CK if severe symptoms.
- 🧪 Check baseline LFTs; routine monitoring no longer required unless symptomatic.
- 🚨 Pregnancy = CONTRAINDICATED (used to be cat X; now reclassified but still avoid).
- 💊 Statin + fibrate (gemfibrozil > fenofibrate) = ↑ rhabdo risk.
- 💊 Simvastatin + amiodarone / diltiazem / verapamil → max simvastatin dose 10–20 mg.
- 📈 High-intensity statins: atorvastatin 40–80 mg, rosuvastatin 20–40 mg (≥50% LDL reduction).
💊 Drugs in This Class
Practice Questions
Which pair of statins is most significantly affected by grapefruit juice through CYP3A4 inhibition, leading to a substantial rise in serum levels and elevated risk of myopathy or rhabdomyolysis?
Sources
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