Makindo Medical Notes

💊 Introduction

Statins (HMG-CoA reductase inhibitors) are first-line lipid-lowering drugs for both primary and secondary prevention of cardiovascular disease. They reduce LDL cholesterol and improve outcomes in coronary artery disease, stroke, and peripheral vascular disease. NICE recommends offering statins (e.g., atorvastatin 20 mg) to adults with a ≥10% 10-year CVD risk (QRISK2/QRISK3).

⚙️ Mechanism of Action

• Competitively inhibit HMG-CoA reductase, blocking hepatic cholesterol synthesis.
• Upregulate LDL receptors on hepatocytes → enhanced clearance of LDL-C.
• Also modestly ↓ triglycerides and ↑ HDL-C.
• Extra effects: plaque stabilization, anti-inflammatory activity, and improved endothelial function.

📌 Indications

• Primary prevention: High CVD risk (≥10% 10-year risk), diabetes, CKD.
• Secondary prevention: Established CVD (MI, stroke, PAD).
• Familial hypercholesterolaemia: As part of lipid-lowering strategy.
• Diabetes: Recommended from age 40 or earlier with additional risks.

💊 Common Statins & Doses

• Atorvastatin: 10–80 mg OD (often 20 mg for primary prevention, 80 mg post-ACS).
• Simvastatin: 10–40 mg OD (less commonly used now due to interactions).
• Rosuvastatin: 5–40 mg OD.
• Pravastatin / Fluvastatin: Less potent, used where interactions are a concern.

🕐 Take in the evening (except atorvastatin/rosuvastatin, long half-life so timing less important).

⚠️ Side Effects

• Muscle-related:
  • Myalgia (normal CK)
  • Myopathy (CK >10× ULN)
  • Rhabdomyolysis (rare but severe; CK >40× ULN, myoglobinuria, risk of AKI)
• Liver: Mild ALT/AST rises; rarely hepatitis.
• Metabolic: Slight ↑ risk of type 2 diabetes in predisposed patients.
• Other: GI upset, headache, rare reversible memory disturbance.

🔗 Key Drug Interactions

• ↑ Risk of toxicity with CYP3A4 inhibitors: macrolides (clarithromycin), azoles, protease inhibitors, grapefruit juice.
• Fibrates + niacin ↑ myopathy risk.
• Safer choices in polypharmacy: pravastatin, rosuvastatin.

🧪 Monitoring

• Check baseline LFTs, lipid profile, CK if muscle history.
• Repeat lipids at 3 months (expect ≥40% LDL-C reduction with atorvastatin 20 mg).
• LFTs only repeated if symptoms or clinically indicated.
• Stop statin if CK >5× ULN or ALT >3× ULN persistently.

🚫 Contraindications

• Active liver disease or unexplained persistent ALT rise.
• Pregnancy & breastfeeding (teratogenic).
• Relative: heavy alcohol use, severe renal/hepatic impairment, frailty.

📊 Evidence & Benefits

• Large RCTs (e.g., 4S, HPS, JUPITER) show ~25–30% reduction in major CV events.
• Greatest benefit seen in secondary prevention (post-MI, stroke).
• Risk reduction is proportional to LDL-C lowering.

✅ Summary

Statins are the cornerstone of lipid management and CVD prevention. They are effective, safe, and widely used. Main risks are muscle-related and liver enzyme elevation, but benefits far outweigh risks. Regular monitoring, patient education (report unexplained muscle pain/weakness), and careful consideration of drug interactions ensure safe prescribing.