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  4. Lipid Lowering Therapy and Cardiovascular Risk Reduction

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

CVD Risk Assessment Guidelines

The QRISK3 risk calculator is recommended to estimate the patient's 10-year CVD risk

 

It would not be too surprising if an exam question asks 'which of the following is a component of the QRISK3 risk calculator?' So, do visit the site to check what information is needed to calculate the 10-year CVD risk.

However, one can just use the online calculator in clinical practice...

 

QRISK3 risk calculator should only be used if:

  • Patient has NO established CVD (coronary artery disease or stroke / TIA), and
  • 25-84 y/o, and
  • NOT taking a statin

Click to view factors that can underestimate CVD risk.

 

A risk assessment tool (including QRISK3 risk calculator) should not be used in the following patients:

  • T1DM - see section below for statin indications
  • CKD - all patients should be on a lipid-lowering therapy for primary prevention (if not secondary prevention) (irrespective of QRISK3)
  • Familial hypercholesterolaemia - all patients should be on a lipid-lowering therapy (see this article)

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

  • The total cholesterol / HDL ratio is a component of the QRISK3 tool
  • Although it is not necessary to calculate the 10-year CVD risk, it will improve the accuracy if available
 

Exclude common secondary causes of dyslipidaemia:

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

Management Guidelines

Refer the following patients for specialist assessment (due to possible familial hypercholesterolaemia - see this article)

  • Total cholesterol >9.0 mmol/L or non-HDL cholesterol >7.5 mmol/L
  • Even in the absence of 1st degree family history of premature coronary heart disease

Refer urgently to a specialist if triglyceride >20 mmol/L and are not secondary to excess alcohol intake / poor glycaemic control
  • To identify genetic lipid disorders or complex metabolic conditions, and
  • Prevent complications like acute pancreatitis

  • 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 monounsaturated and polyunsaturated fats 
  • Encourage physical activity 
  • Weight management 
  • Smoking cessation 
  • Advice on alcohol consumption

There are 2 main scenarios:
 
Scenarior Description
Primary prevention This applies to those with NO established CVD but at increased risk

The purpose of  lipid-lowering therapy in these patients is to prevent the first occurrence of CVD
Secondary prevention This applies to those who already have established CVD

The purpose of lipid-lowering therapy in these patients is to prevent recurrence or worsening of CVD
 

Lipid-lowering therapy for CVD primary prevention is indicated if:

  • QRISK3 score ≥10%
  • CKD
  • T1DM with any of the following
    • >40 y/o 
    • Diabetes for >10 years
    • Established nephropathy
    • Presence of other CVD risk factors 
 
Management:
  • 1st line: atorvastatin 20mg
  • Lipid target for primary prevention: >40% reduction in non-HDL cholesterol

All patients with established CVD should receive lipid-lowering therapy for CVD secondary prevention.
1st line: atorvastatin 80mg (all patients)
  • In patients with CKD, atorvastatin 20mg is 1st line (only consider increasing to 80mg if cholesterol target not met, and eGFR >30)
  • Another reason to give a lower dose is intolerance / patient's preference
  • NICE recommends considering adding ezetimibe to the maximum tolerated intensity and dose of statin to reduce CVD risk further (even if lipid targets are met)


Lipid target for secondary prevention:

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

 

If lipid targets are not met with atorvastatin 80mg

  • Step 1:
    • Ensure adherence
    • Encourage and optimise dietary and lifestyle changes
    • Consider increasing the statin to the maximum tolerated dose and intensity
 
  • Step 2: consider adding any of the following
    • Ezetimibe
    • PCSK9 inhibitors (inclisiran / alirocumab / evolocumab)

Before starting statins, treat comorbidities and secondary causes of dyslipidaemia
 

See the following recommendations if statin is contraindicated or not tolerated, and lipid-lowering therapy is indicated.

 
Indication Step 1 Step 2 (if ezetimibe alone does not meet lipid target)
Primary prevention Ezetimibe monotherapy Ezetimibe + bempedoic acid
Secondary prevention Consider alternative or additional drugs (i.e. alone or in addition to ezetimibe):
  • Bempedoic acid
  • PCSK9 inhibitors (inclisiran / alirocumab / evolocumab)
 

Information Description
Important adverse effects
  • Muscle-related symptoms (muscle pain / weakness / cramp) - most frequently reported side effects
  • Arthralgia
  • GI upset 

Rare:
  • Myositis
  • Hepatitis
  • Rhabdomyolysis (extremely low risk)

Use with caution in those at increased risk of muscle toxicity
Contraindications
  • Pregnancy (stop statin 3 months before attempting to conceive) 
  • Breastfeeding (do not restart until breastfeeding is finished)
Drug interaction Be aware that combining a statin with liver enzyme inhibitors can increase the risk of muscle toxicity

Notable interaction is with grapefruit juice, which is a liver enzyme inhibitor

Timing Tests
Baseline
  • Full lipid profile
  • LFTs
  • Renal function 
  • Diabetes status
  • TSH level (if there are suggestive features of thyroid condition) 
At 2-3 months
  • Full lipid profile
  • LFTs
At 12 months
  • Full lipid profile
  • LFTs 
Beyond 12 months
  • Annual full lipid profile (but not LFTs, unless clinically indicated) 
 

Do NOT routinely measure creatine kinase levels. Only measure if a person on statin develops unexplained muscle pain / tenderness / weakness

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

Lipid profile and LFTs timings summarised:

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

References

Author: Stella Panou, Adams Lau
Reviewer:
Last Edited: 15/09/25