2.12 Lipid-regulating drugs
Generic simvastatin is the preferred initial agent. Simvastatin (tablets), atorvastatin (tablets), rosuvastatin (tablets) and pravastatin (tablets) are 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors (statins) which inhibit the synthesis of cholesterol, especially in the liver. Large-scale clinical studies in both primary and secondary prevention have established the value of these drugs in reducing total mortality, major cardiac events, stroke and the need for subsequent revascularisation. Liver function tests (LFTs) should be monitored regularly. There is little information available on a rational approach to liver-function monitoring; however, a NICE guideline suggests that liver enzymes should be measured before treatment, and repeated within 3 months and at 12 months of starting treatment, unless indicated at other times by signs or symptoms suggestive of hepatotoxicity. Those with serum transaminases that are raised, but less than 3 times the upper limit of the reference range, should not be routinely excluded from statin therapy. Those with serum transaminases of more than 3 times the upper limit of the reference range should discontinue statin therapy. The drugs exert their maximum effect after four weeks. See local statement on the use of statins.
Dose recommendations (adults):
Simvastatin 40mg at night for both primary and secondary prevention - see updated prescribing information for simvastatin regarding interactions that can increase the risk of myopathy and or rhabdomyolysis.
Note that dosing simvastatin above 40mg is not recommended, and if the patient does not reach cholesterol targets on this therapy, the patient should preferably be switched to atorvastatin 40mg then up-titrated as necessary to 80mg.
Atorvastatin 80mg daily if used as secondary prevention in MI or stroke. Lower doses may be used for primary prevention (but not first-line) or if simvastatin is not tolerated/contraindicated.
Rosuvastatin 10mg daily should be started as the initial dose regardless of whether the patient has been on another agent, as using higher doses is associated with a greater risk of adverse effects. Note: Patients of Asian origin or the elderly should be started on a 5mg dose daily.
Bezafibrate (tablets, m/r tablets) is preferred in patients who also have elevated serum triglycerides that could not be reduced to an acceptable level by a statin. Side-effects are common and patients should be warned to expect them and encouraged to persevere with treatment. LFTs should be monitored regularly. It is best used in a once daily regimen, i.e. Bezalip® Mono. No major outcome trials in primary or secondary prevention of coronary heart disease have been reported with bezafibrate.
Ciprofibrate (tablets) is an alternative to bezafibrate when the first choice fibrate has not produced an adequate response.
Extended release nicotinic acid/laropiprant (m/r tablets, Tredaptive®) . Note: 21/01/2013 Tredaptive® - withdrawn throughout the EU after a study has shown a failure to reduce major vascular events and an increase in non-fatal serious adverse events.
Ezetimibe (tablets) inhibits the intestinal absorption of cholesterol. Ezetimibe is not currently recommended in NHSG, see local statement.
Nicotinic acid (tablets) is a second-line agent. It is used in combination with aspirin which reduces the incidence of prostaglandin-associated side-effects, e.g. flushing, dizziness, headache, palpitations and pruritus.
Omega-3 marine triglycerides (capsules, emulsion, liquid, proprietary name, Maxepa®) is a second-line agent for the treatment of severe hypertriglyceridaemia.
PRESCRIBING POINTS FOR LIPID-LOWERING DRUGS
- Although the relative benefits of statin therapy are identical in both primary and secondary prevention, the absolute benefits are considerably greater (approximately ten-fold) for secondary prevention. The greatest priority therefore lies with secondary prevention.
- A lipid lowering diet can be recommended, although its effectiveness is doubtful. In patients with established coronary artery disease, statins should be started before awaiting the outcome of dietary intervention.
- For secondary prevention, consideration could be given to starting a statin if total cholesterol is greater than 3.5mmol/litre. The GMS contract and SIGN aim to treat to a target total cholesterol of 5mmol/litre or less.
- For secondary prevention, it is no longer necessary to perform fasting lipid profiles for the majority of individuals.
- After coronary revascularisation, patients should have their LDL cholesterol reduced to between 2.2 - 2.5mmol/litre. This has been shown to confer significant benefits.
- In primary prevention, raised serum cholesterol is an important risk factor for coronary heart disease, but it should not be considered in isolation. The other major risk factors are smoking, hypertension, family history, diabetes and age.
- The use of statins for primary prevention should be governed by the use of a risk factor table, rather than lipid measurement alone, e.g. the Joint British Societies' guidelines (BNF) or an equivalent risk assessment calculator.
- Drug therapy may occasionally be selected on the basis of the prevailing lipid profile.
- FOR PATIENTS WITH ESTABLISHED VASCULAR DISEASE:
If triglycerides are >10mmol/litre then expert advice should be obtained.
- IN PRIMARY PREVENTION:
If cholesterol or triglycerides are >10mmol/litre then expert advice should be obtained.
- FOR PATIENTS WITH ESTABLISHED VASCULAR DISEASE:
- Both statins and fibrates are rarely associated with muscle pains/myositis. Creatine kinase should be checked if this occurs. Rhabdomyolysis is rare but fatal.