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Lipid modification - primary and secondary CVD prevention - Management
What lipid modification therapy should I offer for secondary prevention if a statin is not suitable?
- Consider offering a fibrate, modified-release nicotinic acid, or a bile acid sequestrant if a statin is not suitable.
- 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, fibrates, and nicotinic acid.
Factors influencing choice | Bile acid sequestrants | Fibrates | Nicotinic acid |
|---|
Evidence for secondary prevention of cardiovascular disease? | | | |
When are these drugs more preferred? | — | People with elevated serum triglycerides | — |
Risk of myopathy or rhabdomyolysis | Not reported* | Rare | Rare |
Common adverse effects | Gastrointestinal Elevated serum triglycerides | Gastrointestinal Skin rashes | Flushing, rash, itching Headaches Gastrointestinal disturbance |
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 muscular adverse effects) | Alcohol (increase flushing) Possibly with warfarin |
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 | Significant hepatic dysfunction Active peptic ulcer disease Arterial bleeding |
Dose titration | Yes | Yes (e.g. fenofibrate) | Yes |
Lipid/lipoprotein effects |
Low-density lipoprotein (LDL) cholesterol | Decreased by 15–30% | Decreased by 5–25% (May be increased in people with high triglycerides) | Decreased by 5–25% |
High-density lipoprotein (HDL) cholesterol | Increased by 5–15% | Increased by 10–20% | Increased by 15–35% |
Triglycerides | No change or increase | Decreased by 20–50% | Decreased by 20–50% |
Additional comments | Poor tolerability and unpalatability limit compliance | — | Rarely prescribed in the UK in the past due to adverse effects |
* Manufacturers of bile acid sequestrants have not reported myopathy and rhabdomyolysis as adverse effects of these drugs. |
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Basis for recommendation
Fibrates, nicotinic acid, and bile acid sequestrants:
- The National Institute for Health and Clinical Excellence (NICE) recommends that a fibrate, nicotinic acid, or a bile acid sequestrant should be considered for secondary prevention of CV events if a person cannot tolerate a statin [NICE, 2007; NICE, 2008a].
- The evidence for fibrates, nicotinic acid and bile acid sequestrants is less robust than that for statins in the secondary prevention of CV events [National Collaborating Centre for Primary Care, 2008a].
- NICE does not state any preference when deciding whether to offer a fibrate, nicotinic acid, or a bile acid sequestrant [National Collaborating Centre for Primary Care, 2008a]. CKS recommends that choice be based on comorbidities, potential for drug interactions, possible adverse effects, and patient preference.
Ezetimibe:
- CKS does not currently recommend the use of ezetimibe for secondary prevention of CVD because:
- There is no evidence to support this use. Ezetimibe is not licensed for secondary 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 secondary prevention of cardiovascular events [National Collaborating Centre for Primary Care, 2008a].
Omega-3 fatty acid supplements:
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