Statins & lipid drugs

Pick the right intensity, know the myopathy, when to add ezetimibe or PCSK9.

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◆Statin intensity (ACC/AHA)

•High-intensity (LDL ↓ ≥ 50%): atorvastatin 40–80, rosuvastatin 20–40
•Moderate-intensity (LDL ↓ 30–49%): atorvastatin 10–20, rosuvastatin 5–10, simvastatin 20–40, pravastatin 40–80
•Low-intensity: rarely indicated; only for intolerance

•Clinical ASCVD (prior MI, stroke, PAD): HIGH intensity (or moderate if >75)
•LDL ≥ 190: high intensity
•Diabetes age 40–75: moderate (high if other ASCVD risk factors)
•Primary prevention 40–75 + 10-yr ASCVD ≥ 7.5%: discuss; ≥20% start moderate-high intensity

•Myalgia (5–10%) — usually benign, check CK if severe
•Rhabdomyolysis (rare, <0.1%) — CK >10× ULN, dark urine, weakness; stop drug
•Statin-induced autoimmune myopathy (anti-HMGCR antibodies) — persistent weakness despite stopping
•Hepatic dysfunction — minor LFT bumps common; only stop if >3× ULN
•New-onset DM (slight ↑ risk; benefits outweigh in most)
•Drug interactions: simvastatin + amiodarone, fibrates, macrolides, fluconazole, cyclosporine → ↑ myopathy risk

•Add EZETIMIBE first (cheap, oral, additional ~20% LDL drop, modest CV benefit)
•Then PCSK9 inhibitors (evolocumab, alirocumab) — injectable, very expensive, big LDL drops, CV mortality benefit
•Bempedoic acid — alternative if statin intolerant, ↓ LDL ~15–20%, modest CV benefit
•Inclisiran — siRNA against PCSK9, q6mo injection

•Fibrates (fenofibrate, gemfibrozil): ↓ TG; use for TG >500 to prevent pancreatitis
•Niacin: rarely used; flushing, hyperglycemia, gout
•Omega-3 (icosapent ethyl): ↓ TG; CV benefit at high doses (REDUCE-IT)
•Bile acid sequestrants (cholestyramine): rarely first-line; GI side effects, drug binding interactions

◆Simvastatin max dose 20 mg with amiodarone (or 10 mg with verapamil/diltiazem) — myopathy risk
◆Pregnancy: STOP statins (category X officially, but emerging data less concerning)
◆ALT 3× ULN or unexplained myalgia → hold statin, work up
◆Niacin + simvastatin: no incremental benefit in CV outcomes (AIM-HIGH), more harm
◆Statin + grapefruit juice → ↑ levels (simvastatin, atorvastatin; pravastatin/rosuvastatin OK)

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