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Lipid modification - primary and secondary CVD prevention - Management
What lipid modification therapy should I offer for primary prevention if statin therapy is not suitable?
- Consider offering a fibrate or a bile acid sequestrant if a statin is contraindicated or not tolerated.
- The decision to select a particular lipid-modifying drug should take into account patient preference and tolerability, comorbidities, multiple drug therapy, and the benefits and risks of treatment.
- Table 1 lists some of the factors influencing drug choice when considering an alternative to a statin.
Clarification / Additional information
Table 1. Summary of features for bile acid sequestrants and fibrates.
Factors influencing choice | Bile acid sequestrants | Fibrates |
|---|
When should it be used? | For primary prevention only when a statin is contraindicated or not tolerated. |
Evidence for primary prevention of cardiovascular disease? | | |
When are these drugs more preferred? | — | People with elevated serum triglycerides |
Risk of myopathy or rhabdomyolysis | Not reported* | Rare |
Common adverse effects | Gastrointestinal Elevated serum triglycerides | Gastrointestinal Skin rashes |
Drug interactions | Uncommon: provided other drugs are taken at least one hour before or 4–6 hours after taking a bile acid sequestant. | Ciclosporin, warfarin (extra monitoring recommended) Statins (increased risk of muscle adverse effects) |
Contraindications | Bowel or biliary obstruction | Severe liver dysfunction Severe renal disorders Gallbladder disease Biliary cirrhosis Chronic or acute pancreatitis (except due to acute pancreatitis caused by severe hypertriglyceridemia) Pregnancy and lactation |
Dose titration | Yes | Yes (e.g. fenofibrate) |
Lipid/lipoprotein effects |
Low-density lipoprotein (LDL) cholesterol | Decreased by 15–30% | Decreased by 5–25% (may be increased in people with high triglycerides) |
High-density lipoprotein (HDL) cholesterol | Increased by 5–15% | Increased by 10–20% |
Triglycerides | No change or increase | Decreased by 20–50% |
Additional comments | Poor tolerability and unpalatability may limit compliance | — |
* Manufacturers of bile acid sequestrants have not reported myopathy and rhabdomyolysis as adverse effects of these drugs. |
|
Basis for recommendation
Fibrates and bile acid sequestrants:
Nicotinic acid:
- Nicotinic acid preparations are not recommended because the NICE Guideline Development Group did not find any randomized controlled trials that compared nicotinic acid with placebo in people at high risk of CVD which reported cardiovascular event outcomes [National Collaborating Centre for Primary Care, 2008a].
Ezetimibe:
- CKS does not currently recommend the use of ezetimibe for primary prevention of CVD because:
- There is no evidence to support this use. Ezetimibe is not licensed for primary prevention of cardiovascular events.
- None of the trials (except one) reported any health-related quality of life or clinical endpoints such as cardiovascular morbidity and mortality.
- Only the SEAS trial reported cardiovascular outcomes [Rossebo et al, 2008]. However, it found no difference in major cardiovascular events, overall mortality and secondary outcomes between people (with mild-to-moderate asymptomatic aortic stenosis) who received simvastatin only or a combination of simvastatin and ezetimibe.
- There is some concern about the risk of cancer with ezetimibe. Although there is currently insufficient evidence to draw any conclusions about the effect of ezetimibe on cancer, the Commission on Human Medicines (CHM) will review this issue when the results of two large ongoing ezetimibe trials become available [MHRA, 2008]. Consequently, CKS advises caution until this issue is clarified.
Plant stanols and steroids:
- These are not recommended because the NICE Guideline Development Group did not identify any randomized controlled trials that investigated their effectiveness in the primary prevention of cardiovascular events [National Collaborating Centre for Primary Care, 2008a].
Omega-3 fatty acid supplements:
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