Second-line lipid-modifying drug therapy

First-line therapy with a statin is usually well tolerated, and given their cardiovascular morbidity and mortality benefit, long-term adherence to statin therapy is a priority. For advice on managing adverse effects associated with statins, see Adverse effects of statins.

If statin therapy is not tolerated after reasonable attempts to reintroduce therapy (see Management of suspected statin-associated muscle symptoms), monotherapy with either ezetimibe or a PCSK9 inhibitor is a reasonable alternative. However, the effects of these drugs on cardiovascular outcomes have only been studied when given in combination with statin therapy.

Colestyramine, fenofibrate and nicotinic acid have traditionally been used for lipid modification when other therapies have not been effective. However, there is no evidence to support their use to reduce cardiovascular eventsAIM-HIGH Investigators, 2011HPS THRIVE Collaborative Group, 2014Das Pradhan, 2022. They are not recommended for LDL-C lowering unless all other options for lipid-lowering drug therapy have been exhausted and are usually prescribed under specialist guidance. Fenofibrate may be indicated for patients with elevated triglycerides, and should be considered in patients with diabetic retinopathy (irrespective of the patient’s lipid concentrations) to slow the progression of retinopathyAccord Study Group, 2010.