Pharmacological treatment of dyslipidemia

General points

The benefit of lipid-modulating therapies may be improved by adapting a tailored approach for each patient. This may involve different strategies and therapies, including a combination of lipid-regulating drugs. Moreover, the accompanying drugs and the potential for interactions may influence the decision to use one drug or another.
Lifestyle changes are always the first-line treatment if lipid targets are not met. Exceptions are patients with coronary heart disease or extreme lipid levels, who should receive immediate drug treatment in addition to lifestyle advice.

Which drug for which lipoprotein alterations?

Drug therapy should focus on the lipoprotein fraction that is principally affected. Apart from the individual lipoprotein disorder, treatment strategies and goals depend on the global risk situation of the individual patient.

High-risk patients

LDL target levels required in high-risk patients may be achieved by a high dose of a statin alone or by a combination of a statin and ezetimibe. Ezetimibe alone lowers LDL cholesterol by about 20%. This effect is independent of the LDL cholesterol-lowering effect of statins and is theoretically equivalent to a sixfold increase in the statin dose because doubling the statin dose generally produces a further 6% decrease in LDL cholesterol levels.
The choice of statin may depend on the co-medication. About 60% of all drugs are catabolized by CYP3A4 isoenzyme. Fluvastatin, rosuvastatin and pravastatin are not catabolized by this system and may therefore be considered in situations with an increased risk for side effects due to high statin doses and/or co-medication with other drugs catabolized by CYP3A4.
As dyslipidemic patients remain at high residual vascular risk despite treatment for high LDL cholesterol in accordance with current standards of care, a multifactorial intervention involving combination therapy (e.g. simvastatin + fenofibrate; simvastatin + nicotinic acid) targeting all lipid goals is recommended. Ongoing outcomes studies, i.e., ACCORD, AIM-HIGH and HPS2-THRIVE, will provide important information about the risk and benefit of combination therapy.

Combined hyperlipidemias

The primary goal is lowering LDL cholesterol. Special problems may arise from concomitant increases in triglycerides. In these cases statins may be less effective for LDL lowering and triglycerides may be inappropriately treated.
The combination of a statin (preferentially fluvastatin, rosuvastatin or pravastatin, which are not metabolized by CYP3A4 ) and fenofibrate (gemfibrozil is contraindicated) or the combination of a statin with nicotinic acid may be used under close supervision.
The addition of omega-3 fatty acids to these combinations may be useful if triglyceride target levels have not been reached.

Patients with low HDL

Men with low HDL cholesterol levels usually show less benefit when treated with statins.
The combination of statins with nicotinic acid or fenofibrate may be particularly beneficial in patients with increased LDL cholesterol and decreased HDL cholesterol levels.

Patients with high levels of Lp(a) and of LDL cholesterol

Patients who have increased LDL and Lp(a) levels are at increased risk. Lp(a) may be
effectively lowered by nicotinic acid.
The combination of a statin with nicotinic acid may provide additional benefit.

Patients with high triglyceride levels

Treatment of increased triglyceride levels depends on the nature of the triglyceride increase. In chylomicronemia (exogenous hypertriglyceridemia), elevation of triglycerides is usually much more severe than in hypertriglyceridemia due to elevation of VLDL (endogenous hypertriglyceridemia). Chylomicronemia may be effectively treated by a low-fat diet, restriction of easily resorbable carbohydrates and alcohol abstinence.
For endogenous hypertriglyceridemia, in addition to dietary measures, fibrates are
the most efficacious drugs.
The association of omega-3 fatty acids to fibrates may be useful to further lower triglyceride levels.