Expansion
Statins inhibit HMG-CoA reductase; ezetimibe blocks absorption; PCSK9 inhibitors preserve LDL receptors
Expansion
- Statins: inhibit HMG-CoA reductase. The resulting fall in intracellular cholesterol upregulates LDL receptors, which is the main mechanism of LDL lowering
- Ezetimibe: blocks intestinal cholesterol absorption; added when statins are insufficient or not tolerated
- PCSK9 inhibitors (alirocumab, evolocumab): prevent LDL receptor degradation, giving very large LDL reductions; injectable and expensive
- Fibrates: PPAR-alpha agonists, mainly lowering triglycerides
- Bile acid sequestrants: interrupt enterohepatic circulation
- Icosapent ethyl and omega-3 for hypertriglyceridaemia
Statin adverse effects
- Myalgia is common; myositis with raised creatine kinase is uncommon; rhabdomyolysis is rare but serious
- Risk increased by fibrates (especially gemfibrozil), macrolides, azoles, ciclosporin, amiodarone, grapefruit juice, hypothyroidism and renal impairment
- Deranged liver enzymes, usually mild and transient
- Slightly increased incidence of diabetes
Contraindicated in pregnancy, since cholesterol is required for fetal development.
Check baseline lipids, liver function, creatine kinase, renal function, thyroid function and HbA1c before starting, and remember that muscle symptoms without a raised creatine kinase rarely require stopping permanently.