Lipid-regulating drugs

2.12 Lipid-regulating drugs

Preventative measures should be taken in individuals with a high risk of developing cardiovascular disease (primary prevention) and to prevent recurrence of events in those with established cardiovascular disease (secondary prevention).

Individuals at high risk include those who already have atherosclerotic disease, those with diabetes mellitus aged over 40 years, and those with familial hyper- cholesterolaemia. The risk also increases with age; those over 75 years are at particularly high risk, espe- cially if they smoke or have hypertension.

Preventative measures are also required for other indi- viduals who may be at high risk of developing athero- sclerotic cardiovascular disease; those with a 10-year

risk of cardiovascular disease 1 of 20% or more stand to benefit most from drug treatment. The risk is assessed on the basis of lipid concentration as well as smoking status, blood pressure, gender, and age; other risk fac- tors, such as premature menopause, ethnicity, obesity, triglyceride concentration, chronic kidney disease, impaired glucose tolerance, and a family history of premature cardiovascular disease, should also be taken into account when assessing risk in individual patients.

Lowering the concentration of low-density lipoprotein (LDL) cholesterol and raising high-density lipoprotein (HDL) cholesterol slows the progression of athero- sclerosis and may even induce regression. All patients at high risk of cardiovascular disease should be advised to make lifestyle modifications that include beneficial changes to diet, exercise, weight management, alcohol consumption, and smoking cessation. Lipid-regulating drug treatment must be combined with advice on diet and lifestyle measures, lowering of raised blood pres- sure (section 2.5), the use of low-dose aspirin (section 2.9), and management of diabetes (section 6.1).

The prescribing of drug therapy in homozygous familial hypercholesterolaemia should be undertaken within a specialist centre.

A statin (see below) reduces the risk of cardiovascular disease events, irrespective of serum cholesterol con- centration, and is the drug of first choice for primary and secondary prevention of cardiovascular disease. If statins are contra-indicated or not tolerated, a fibrate (p. 144) or a bile acid sequestrant (p. 143) may be considered for primary or secondary prevention; nico- tinic acid (p. 146) is also an option for secondary pre- vention. Fibrates, bile acid sequestrants, or nicotinic acid should not be used in combination with a statin for primary prevention of cardiovascular disease. In secondary prevention of cardiovascular events, consid- er adjusting doses of lipid-regulating drugs if a total cholesterol concentration of less than 4 mmol/litre or a LDL-cholesterol concentration of less than 2 mmol/litre is not achieved with initial treatment.

A statin is also the drug of first choice for treating hypercholesterolaemia and moderate hypertriglyceri- daemia. Severe hyperlipidaemia not adequately con-

trolled with a maximal dose of a statin may require the use of an additional lipid-regulating drug such as ezetimibe or colestyramine; such treatment should

generally be supervised by a specialist.

A number of conditions, some familial, are characterised by very high LDL-cholesterol concentration, high trigly- ceride concentration, or both. A fibrate is added to statin therapy if triglycerides remain high even after the LDL-cholesterol concentration has been reduced adequately; nicotinic acid may also be used to further lower triglyceride or LDL-cholesterol concentration.

Combination of a statin with a fibrate or with nicotinic acid carries an increased risk of side-effects (including rhabdomyolysis—see CSM advice below) and should be used under specialist supervision; monitoring of liver function and creatine kinase should also be considered. The concomitant administration of gemfibrozil with a statin increases the risk of rhabdomyolysis consider- ably—this combination should not be used.

Patients with hypothyroidism should receive adequate thyroid replacement therapy before assessing the requirement for lipid-regulating treatment because cor- recting hypothyroidism itself may resolve the lipid abnormality. Untreated hypothyroidism increases the risk of myositis with lipid-regulating drugs.

CSM advice (muscle effects) The CSM has advised that rhabdomyolysis asso- ciated with lipid-regulating drugs such as the fibrates and statins appears to be rare (approx. 1 case in every 100 000 treatment years) but may be increased in those with renal impairment and pos- sibly in those with hypothyroidism (see also notes above). Concomitant treatment with drugs that increase plasma-statin concentration increase the risk of muscle toxicity; concomitant treatment with

a fibrate and a statin may also be associated with an increased risk of serious muscle toxicity.