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Lipid Lowering Therapy and Cardiovascular Risk Reduction

NICE guideline [NG238] Cardiovascular disease: risk assessment and reduction, including lipid modification. Published: Dec 2023. This article does NOT include information regarding familial hypercholesteremia.

Background Information

Dyslipidaemia: imbalance of serum lipids (including high total cholesterol, high LDL cholesterol, high triglycerides, and/or low HDL cholesterol) 

 

Primary prevention of CVD: targets patients with NO history of CVD but are at risk of a first cardiovascular event  

Secondary prevention of CVD: targets patients with established CVD to decrease the risk of a recurrent cardiovascular event

Common high-intensity statins:

  • Atorvastatin 20mg to 80mg
  • Rosuvastatin 10mg to 40mg
  • Simvastatin 80mg
 

Intensity of a statin is based on the % reduction in LDL cholesterol it can produce.

Statin intensity  % reduction in LDL Drug and dose
High intensity           >40%  Atorvastatin 20, 40, 80mg 
Rosuvastatin 10, 20, 40mg
Simvastatin 80mg 
Medium intensity         30-40% Atorvastatin 10mg 
Rosuvastatin 5mg 
Simvastatin 20, 40mg
Fluvastatin 80mg 
Low intensity           <30%  Simvastatin 10mg
Fluvastatin 20, 40mg 
Pravastatin 10, 20, 40mg

Guidelines

QRISK3 tool is recommended to estimate the 10-year CVD risk. 

 

QRISK3 tool is only recommended in:

  • Patients WTIHOUT established CVD
  • 25-84 y/o

Click to view factors that can underestimate CVD risk.

 

NICE recommends NOT to use a risk assessment tool in:

  • T1DM
  • eGFR <60 mL/min and/or albuminuria 
  • Familial hypercholesterolaemia 
 

Recommendations on risk reduction in these patients do NOT dependent on 10-year CVD risk.

  • Healthy eating 
  • Cardioprotective diet 
    • Total fat intake </=30% of total energy intake
    • Saturated fat intake </=7% of total energy intake 
    • ↓ Saturated fat intake 
    • Replace saturated fats with mono-unsaturated and polyunsaturated fats 
  • Encourage physical activity 
  • Weight management 
  • Smoking cessation 
  • Advise on alcohol consumption

To best estimate CVD risk, measure total blood cholesterol and HDL cholesterol

Exclude common secondary causes of dyslipidaemia:

  • Excess alcohol intake
  • Uncontrolled diabetes
  • Hypothyroidism 
  • Liver disease
  • Nephrotic syndrome 
 

Refer the following for specialist assessment:

  • Total cholesterol >9.0 mmol/L, or
  • Non-HDL cholesterol >7.5
  • +/- 1st degree FHx of premature coronary artery disease

Before starting statin therapy:

  • Optimise lifestyle changes and offer to re-assess CVD risk after lifestyle changes 
  • Treat comorbidities and secondary causes of dyslipidaemia 
 

Indications for statin therapy for primary prevention of CVD:

  • QRISK3 score >/=10% 
  • Ineffective / inappropriate lifestyle changes 
 

1st line lipid lowering therapy: atorvastatin 20mg PO OD

Lipid target for primary prevention: >40% reduction in non-HDL cholesterol

This is regardless for T1DM and T2DM

  • 1st line lipid lowering therapy: atorvastatin 80mg PO OD in ALL patients 
  • If maximum tolerated dose and intensity of statin is ineffective → consider adding ezetimibe 


Lipid target for secondary prevention:

  • LDL cholesterol </=2.0 mmol/L, or
  • Non-HDL cholesterol </=2.6 mmol/L

Important adverse effects:
  • Small risk of muscle pain, tenderness, weakness 
  • Extremely low risk of rhabdomyolysis 
  • Arthralgia 
  • GI up set 


Use with caution in:

  • Patients at increased risk of muscle toxicity


Possible drug interactions:

  • Grapefruit juice and some supplements may interfere with statins
  • Always consult someone when starting other drugs or thinking about taking supplements 


Contraindications:

  • Pregnancy (stop statin 3 months before attempting to conceive) 
  • Breastfeeding (do not restart until breastfeeding is finished)
 

Baseline tests 
  • Full lipid profile
  • LFTs
  • Renal function 
  • Diabetes status
  • TSH level (if there is suggestive features of thyroid condition) 

2-3 months after starting or changing 
  • Full lipid profile
  • LFTs

At 12 months 
  • Full lipid profile
  • LFTs 
 

Then → annual full lipid profile (but not LFTs, unless clinically indicated) 
 

Do NOT routinely measure CK levels. Measure if a person on statin develops unexplained muscle pain / tenderness / weakness

  • If CK level <5 times upper limit → unlikely due to statin + investigate for other possible causes
  • If CK level >5 times upper limit → repeat after 7 days
    • If still >5 times→ discontinue statin  
    • If elevated but <5 times → lower dose

 

Lipid profile and LFTs timings summarised:

  • Lipid profile: baseline (0 months), 2-3 months after, 12 months after, then anually 
  • LFTs: baseline (0 months), 2-3 months after, no more repeat (unless clinically indicated)

Statin indicated for primary prevention of CVD in ANY of the following:
  • >40 y/o 
  • Diabetes for >10 years
  • Established nephropathy
  • Presence of other CVD risk factors 


Regardless of primary or secondary prevention: start with atorvastatin 20mg

  • Targets are the same
    • Primary prevention: ≥40% reduction in non-HDL cholesterol
    • Secondary prevention: LDL cholesterol ≤2.0 OR non-HDL cholesterol ≤2.6
 

Regardless of primary or secondary prevention: start with atorvastatin 20mg

Targets are the same
  • Primary prevention: ≥40% reduction in non-HDL cholesterol
  • Secondary prevention: LDL cholesterol ≤2.0 OR non-HDL cholesterol ≤2.6 

If target not met + eGFR >/=30 mL/min/1.73m2 → increase dose

Add on therapy to statins (prescribed by specialists) 

  • 1st line → ezetimibe (for both primary/secondary prevention) 
  • 2nd line → consider alirocumab / bempedoic acid, evolocumab, inclisiran
NICE have seperate  guidance on the use of these additional lipid-lowering treatments along with very specific and detailed criteria. 

 

If statin therapy is inappropriate → Ezetimibe monotherapy can be used

References

Author: Stella Panou 
Reviewer: TBC 
Last Edited: 11/01/25