Lipid Lowering Therapy and Cardiovascular Risk Reduction
Lipid lowering therapy is central to preventing atherosclerotic cardiovascular disease by reducing LDL cholesterol and overall vascular risk.
This article covers hyperlipidaemia causes, complications, cardiovascular risk assessment (QRISK3), primary and secondary prevention and lipid-lowering therapy (statins, ezetimibe, bempedoic acid, PCSK9 inhibitors). It is based on NICE guideline [NG238] Cardiovascular disease: risk assessment and reduction, including lipid modification.
Background Information
Definitions
Dyslipidaemia: abnormal concentration of serum lipids (including high total cholesterol, high LDL cholesterol, high triglycerides, and/or low HDL cholesterol)
Hyperlipidaemia: elevated blood lipid levels (including total cholesterol, LDL cholesterol, triglycerides)
Hyperlipidaemia Causes
Primary causes: genetic disorders that affect lipid metabolism
- Familial hypercholesterolaemia – most common (see the Familial Hypercholesterolemia (FH) article)
- Familial dysbetalipoproteinemia
- Familial hypertriglyceridemia
Secondary causes: [Ref1, Ref2]
| Category | Common causes |
|---|---|
| Lifestyle |
|
| Medical conditions | Metabolic conditions:
Hypoalbuminaemia-related (hypoalbuminaemia triggers the liver to increase lipoprotein synthesis in attempt to increase the plasma oncotic pressure):
|
| Drugs |
|
Complications
Direct complications of hyperlipidaemia include: [ref]
- Atherosclerotic cardiovascular disease (e.g. coronary artery disease, cerebral vascular disease, peripheral arterial disease)
- Hepatic steatosis and NAFLDNon-alcoholic fatty liver disease
- Hypertriglyceridaemia-induced pancreatitis (usually occurs in severe hypertriglyceridaemia)
Classification of Statins
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
Clinical Tools
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 Factors outlined by NICE:
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)
Lipid Measurement and Assessment
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
The rationale for managing hyperlipidaemia is to reduce the risk of atherosclerotic cardiovascular disease.
Referral Criteria
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 a family history of premature coronary heart disease
Refer urgently to a specialist if triglycerides are >20 mmol/L and not secondary to excess alcohol intake / poor glycaemic control
- To identify genetic lipid disorders or complex metabolic conditions, and
- Prevent complications like acute pancreatitis
Lifestyle Changes / Conservative Management
- 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
Lipid-Lowering Therapy
Indications
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 |
Primary Prevention
Apart from lipid-lowering therapy, NICE emphasis on optimising lifestyle changes in primary prevention:
- Before offering statin treatment for primary prevention, discuss the benefits of lifestyle changes and optimise the management of all other modifiable CVD risk factors if possible
- Offer people the opportunity to have their risk of CVD assessed again after they have tried to change their lifestyle
If lifestyle change is ineffective or inappropriate → offer statin treatment
Indications to offer lipid-lowering therapy for CVDCardiovascular disease primary prevention:
- QRISK3 score ≥10%
- CKDChronic kidney disease
- T1DMType 1 diabetes mellitus with any of the following
- >40 y/o
- Diabetes for >10 years
- Established nephropathy
- Presence of other CVDCardiovascular disease risk factors
Lipid-lower therapy:
- 1st line: atorvastatin 20 mg
- Target for primary prevention: >40% reduction in non-HDL cholesterol
Secondary Prevention
All patients with established CVD Including:
should receive lipid-lowering therapy for CVDCardiovascular disease secondary prevention.
1st line: atorvastatin 80 mg (all patients)
- In patients with CKDChronic kidney disease, atorvastatin 20 mg is 1st line (only consider increasing to 80 mg 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)
Statin Therapy
Before starting statins, treat comorbidities and secondary causes of dyslipidaemia
Alternative to Statin
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 acidMoA: ATP-citrate lyase inhibitor - upstream of HMG-CoA reductase |
| Secondary prevention | Consider alternative or additional drugs (i.e. alone or in addition to ezetimibe):
|
Safety Information
| Information | Description |
|---|---|
| Important adverse effects |
Rare:
Use with caution in those at increased risk of muscle toxicity |
| Contraindications |
|
| 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 |
Treatment Monitoring and Follow-Up
| Timing | Tests |
|---|---|
| Baseline |
|
| At 2-3 months |
|
| At 12 months |
|
| Beyond 12 months |
|
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
Related Articles
Familial Hypercholesterolemia (FH)
Type 1 Diabetes Mellitus (T1DM)