420.3 🩺 內科專科考前版

420.3.0.1 📌 䞀頁重點

  • 22E updates:
    • Inclisiran (Leqvio) approved 2021 — Q6 mo siRNA against PCSK9
    • Bempedoic acid (Nexletol/Nilemdo) + CLEAR Outcomes (2023) — CV reduction in statin-intolerant
    • Olpasiran anti-Lp(a) siRNA phase 3 (Lp(a) elevation independent ASCVD)
    • Pelacarsen anti-Lp(a) ASO phase 3
    • Evinacumab (Evkeeza) anti-ANGPTL3 for HoFH (FDA 2021)
    • Resmetirom (THRβ agonist) for NASH (FDA 2024) — affects lipid + steatohepatitis
    • AHA/ACC/Multisociety 2023 guideline update: PREVENT calculator (replacing Pooled Cohort Equation)
    • ESC 2019 + 2024: LDL < 55 for very high risk
  • Taiwan: 健保 statin (multiple) 充分; 健保 ezetimibe; 健保 PCSK9 inhibitor 條件 (FH or refractory); 健保 fenofibrate; 健保 omega-3; inclisiran + bempedoic acid + evinacumab 自費 倚 / 條件; CTAOH/TES + Lipid Society Taiwan 指匕

420.3.0.2 🌟 Pearls (15)

420.3.0.2.1 Pharmacology
  1. Statin pleiotropic effects: anti-inflammatory, plaque stabilization beyond LDL lowering
  2. CYP3A4 metabolizers (atorvastatin, simvastatin, lovastatin): grapefruit, macrolide, azole interactions
  3. Rosuvastatin + pravastatin less CYP3A4 — safer with interactions
  4. Statin + gemfibrozil myopathy contraindication; statin + fenofibrate generally OK
  5. Bempedoic acid only liver: no muscle SE; ideal for statin intolerant
  6. PCSK9 inhibitor outcomes (FOURIER, ODYSSEY): MACE reduction beyond LDL effect
420.3.0.2.2 Trials
  1. REDUCE-IT (icosapent ethyl 4 g/d): MACE reduction in TG 135-499 with statin; mechanism unclear
  2. STRENGTH (mixed omega-3): negative — important to specify icosapent ethyl
  3. JUPITER (rosuvastatin in low-LDL high-CRP): primary prevention benefit
  4. TIMI 22 PROVE-IT: high-intensity > standard for ACS
420.3.0.2.3 Practical
  1. Statin myalgia: try alternative statin, lower dose, q-other-day; if persistent + CK normal, consider non-statin
  2. Lp(a) once-in-lifetime measurement: > 50 mg/dL or > 125 nmol/L = elevated
  3. Familial chylomicronemia (FCS): severe TG > 1000; volanesorsen + extreme low-fat
  4. Hypertriglyceridemic pancreatitis acute treatment: insulin (DM) ± plasmapheresis
  5. Pregnancy + dyslipidemia: stop statin; bile acid sequestrant + lifestyle; possibly fish oil

420.3.0.3 📍 Taiwan + 健保

420.3.0.3.1 Drugs
  • 健保 statin (atorvastatin, rosuvastatin, simvastatin, pravastatin, fluvastatin, pitavastatin) — 充分
  • 健保 ezetimibe + Atozet (statin + ezetimibe combo)
  • 健保 PCSK9 inhibitor (alirocumab, evolocumab) 條件 (HeFH/HoFH or 䞍耐 / refractory)
  • 健保 fenofibrate + gemfibrozil (條件)
  • 健保 icosapent ethyl (Vascepa) 條件 (限制)
  • 健保 omega-3 mixed
  • 健保 niacin (rare use)
  • 健保 bile acid sequestrant (cholestyramine, colestipol, colesevelam)
  • Inclisiran (Leqvio) 自費 倚 / 條件 expanding
  • Bempedoic acid 自費 倚
  • Evinacumab 自費 (HoFH; rare)
  • Lomitapide 自費 (HoFH)
  • Mipomersen withdrawn
420.3.0.3.2 Workup
  • 健保 lipid panel (fasting)
  • 健保 ApoB (條件)
  • 健保 Lp(a) (條件)
  • 健保 genetic testing for FH (條件; 限制)
  • 健保 LDL apheresis 條件 (severe HoFH; medical center)
420.3.0.3.3 孞會 + 指匕
  • TES + Taiwan Lipid Society + DAROC
  • ACC/AHA Guideline 2018 + Multisociety 2023
  • ESC/EAS Guideline 2019 + 2024
  • IAS, NLA Recommendations
  • DAROC for diabetes-related dyslipidemia

420.3.0.4 🎓 內專必懂 (15)

  1. Lipoprotein metabolism comprehensive + apoproteins
  2. Statin classes + intensity + indications
  3. Statin SE + interactions (CYP3A4 caveat)
  4. Ezetimibe combination + IMPROVE-IT
  5. PCSK9 inhibitor outcomes (FOURIER, ODYSSEY)
  6. Inclisiran siRNA paradigm (22E)
  7. Bempedoic acid (CLEAR Outcomes) for statin intolerant
  8. Icosapent ethyl (REDUCE-IT) for TG + CV (vs STRENGTH negative for mixed omega-3)
  9. Familial hypercholesterolemia (HeFH/HoFH) workup + treatment
  10. Lp(a) measurement + olpasiran
  11. HoFH apheresis + evinacumab/lomitapide
  12. Type III dysbetalipoproteinemia (ApoE2/E2)
  13. LPL deficiency + volanesorsen
  14. Hypertriglyceridemic pancreatitis acute management
  15. 22E new: inclisiran, bempedoic acid, evinacumab, olpasiran, resmetirom NASH

420.3.0.5 ⚙ AHA/ACC/Multisociety 2023 Quick (內專)

Risk Stratification:
- ASCVD: established disease (secondary prevention)
- Very high risk: ASCVD + multiple high-risk conditions
- LDL ≥ 190: regardless of age (FH consider)
- DM age 40-75: risk-stratified
- 10-yr ASCVD ≥ 7.5%: statin candidate
- PREVENT calculator (2023): replaces Pooled Cohort Equation

Treatment Algorithm:
1. Lifestyle (always)
2. Statin (intensity by risk):
   - Very high risk: high-intensity, goal LDL < 55-70
   - High risk: high-intensity, < 70
   - Moderate risk: moderate-intensity, < 100
3. Add ezetimibe if not at goal
4. Add PCSK9 inhibitor if still not at goal (esp. ASCVD secondary prevention)
5. Add inclisiran (Q6 mo SC) for adherence-favorable PCSK9 alternative
6. Bempedoic acid for statin intolerant
7. Lp(a) elevated → aggressive risk modification + consider clinical trial / olpasiran

420.3.0.6 ⚙ Statin Intolerance Algorithm

Step 1 — Confirm "intolerance":
- Symptoms: muscle pain (myalgia, myopathy)
- CK elevation (rule out rhabdo)
- LFT elevation
- Serial trials with adequate washout

Step 2 — Rule out other causes:
- Hypothyroidism (TSH)
- Vit D deficiency (replace)
- Q10 deficiency (controversial; supplement trial)
- Drug interaction (grapefruit, macrolide, fibrate)

Step 3 — Try alternatives:
- Switch statin (e.g., simvastatin → rosuvastatin or pravastatin)
- Lower dose
- Every-other-day dosing
- Combine with ezetimibe to reduce statin needed

Step 4 — Non-statin options:
- Ezetimibe (full dose)
- PCSK9 inhibitor
- Bempedoic acid (CLEAR Outcomes)
- Inclisiran
- Combination

Step 5 — Severe muscle issue:
- Rhabdomyolysis → stop statin immediately
- Genetic testing (SLCO1B1 polymorphism — simvastatin myopathy risk)

420.3.0.7 ⚙ Hypertriglyceridemic Pancreatitis Acute Treatment

Step 1 — Recognition:
- TG > 1000 + acute pancreatitis (TG accounts for ~ 5-10% pancreatitis)
- Serum often lipemic appearance
- Lipase elevation

Step 2 — Acute Treatment:
- NPO + IV fluids
- Pain control
- Insulin (if DM): activates LPL, lowers TG
- IV regular insulin 0.1-0.3 U/kg/hr + D5 to maintain glucose
- Heparin (controversial; activates endothelial LPL)
- **Plasmapheresis** for severe / persistent / multi-organ

Step 3 — Sub-acute (after stabilization):
- Extreme low-fat diet (< 15% calories)
- Fenofibrate 145 mg/d
- Omega-3 (high-dose)
- Avoid alcohol
- Treat secondary cause (DM, hypothyroid)

Step 4 — Long-term:
- Genetic testing if recurrent or familial pattern (LPL, ApoC-II, ApoA-V, GPIHBP1 mutations)
- Volanesorsen (anti-ApoC-III) for severe LPL deficiency / FCS
- Lifestyle + adherence

⚠ AI 草皿。