1. Background information

a. Definition

• HMG-CoA reductase inhibitors
• First-line lipid-lowering therapy for cardiovascular disease (CVD) prevention
• Examples: atorvastatin, simvastatin, rosuvastatin
• Reduce LDL (“bad”) cholesterol

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b. Mechanism of action

• Inhibit HMG-CoA reductase (rate-limiting step in cholesterol synthesis)
• ↓ hepatic cholesterol → ↑ LDL receptor expression → ↑ LDL clearance
• Additional effects:
  • Plaque stabilisation
  • Anti-inflammatory effects

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c. Indications (NICE NG238 aligned)

• Primary prevention
  • ≥10% 10-year CVD risk (QRISK)
• Secondary prevention
  • Established CVD (MI, stroke, PAD)
• Diabetes (Type 1 & 2)
• Chronic kidney disease
• Familial hypercholesterolaemia

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2. Assessment

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a. Contra-indications

Absolute:

• Active liver disease
• Unexplained persistent ↑ transaminases
• Pregnancy / breastfeeding

Caution:

• Heavy alcohol use
• Hypothyroidism (↑ myopathy risk)
• Renal impairment
• History of statin intolerance

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b. Drug interactions (HIGH-YIELD)

Increase statin levels → ↑ myopathy risk:

• Macrolides (clarithromycin, erythromycin)
• Azole antifungals
• Amiodarone
• Verapamil / diltiazem
• Grapefruit juice

👉 Especially important for simvastatin

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c. Toxicity

1. Muscle toxicity (KEY EXAM TOPIC)

• Myalgia (common)
• Myopathy (↑ CK)
• Rhabdomyolysis (rare, life-threatening)

2. Hepatic

• ↑ ALT/AST (usually mild, reversible)

3. Metabolic

• Slight ↑ risk of type 2 diabetes

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d. ECG features

• ❌ No specific ECG changes

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e. Monitoring (WITH TIMELINES – VERY HIGH YIELD)

Baseline (before starting)

• Lipid profile
• LFTs (ALT)
• HbA1c (if diabetes risk)
• CK (only if muscle symptoms or high risk)

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After initiation / dose change

• LFTs:
  • At 3 months
  • At 12 months
  • Not routinely thereafter unless indicated

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Lipid monitoring

• Repeat at 3 months
  • Aim: ≥40% reduction in non-HDL cholesterol (NICE target)

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CK monitoring

• NOT routine
• Check only if:
  • Muscle symptoms
  • High-risk patient

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Ongoing monitoring

• Lipids:
  • Annually (or as clinically indicated)
• LFTs:
  • Only if clinically indicated

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Clinical monitoring

• Ask about:
  • Muscle pain/weakness
  • Adherence
  • Lifestyle factors

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3. Management (NICE CKS aligned)

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a. Side effects AND what to do

Side effect	Action
Mild muscle pain	Continue + monitor
Severe muscle pain / weakness	Check CK
CK >5× ULN	STOP statin
Suspected rhabdomyolysis	URGENT admission
↑ LFTs (<3× ULN)	Continue + monitor
↑ LFTs (>3× ULN)	STOP statin
GI symptoms	Reassure / adjust dose

👉 If intolerance:

• Try different statin
• Use lower dose or alternate-day dosing

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b. Use in Primary Care

• Main setting of prescribing
• Initiation and titration done in GP
• Common regimen:
  • Atorvastatin 20 mg (primary prevention)
  • Atorvastatin 80 mg (secondary prevention)
• GP responsibilities:
  • Risk assessment (QRISK)
  • Monitoring (lipids, LFTs)
  • Lifestyle counselling

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c. Use in Secondary Care

• Initiation post:
  • Acute coronary syndrome
  • Stroke/TIA
• High-intensity therapy:
  • Atorvastatin 80 mg (unless contraindicated)
• Specialist involvement:
  • Statin intolerance
  • Familial hypercholesterolaemia
  • Complex dyslipidaemia

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🔑 AKT ULTRA-HIGH YIELD SUMMARY

• MOA = ↓ cholesterol synthesis → ↑ LDL clearance
• Indications = primary + secondary CVD prevention
• Target = ≥40% ↓ non-HDL cholesterol
• Check LFTs at baseline, 3 months, 12 months
• Myalgia = common, rhabdomyolysis = rare
• CK only if symptoms
• STOP if CK >5× ULN or ALT >3× ULN
• No ECG changes