2nd April 2024

Hyperlipidaemia medications

After lifestyle modifications, statins play a major role in treatment of hyperlipidaemia and are effective when taken at night, coinciding with peak endogenous cholesterol synthesis. Other lipid regulators include niacin, bile acid sequestrants, fibrates, and ezetimibe.

Statins

Statins, such as simvastatin, work by competitively inhibiting HMG-CoA reductase to reduce hepatic cholesterol synthesis. They are most effective at lowering LDL-C but less effective than fibrates at lowering triglyceride levels. Common side effects include fatigue, headache, nausea, indigestion, and change in bowel habits. Significant but rarer side effects include statin-induced myopathy, hepatotoxicity, and statin-induced diabetes. 

Statin-induced myopathy incorporates the spectrum of myalgia, myositis, rhabdomyolysis, and raised creatine kinase (CK). The mean duration of treatment before the onset of symptoms is six months. It affects 10-15% of patients and is characterised by muscle and tendon pain, stiffness, and cramping. Although rare, it may lead to life-threatening rhabdomyolysis. The risk of statin-induced myopathy is increased by:

• Dietary intake of grapefruit or cranberry juice.
• Co-prescription of drugs that inhibit cytochrome P450 CYP3AE (fibrates, nicotinic acid, calcium-channel blockers, ciclosporin, amiodarone, macrolide antibiotics, azole antifungals, and protease inhibitors). 
• Genetic factors, such as polymorphisms in cytochrome P450 isoenzymes that increase the risk of statin-induced myopathy

CK levels are not routinely monitored unless the patient is symptomatic. Where the patient describes symptoms and CK levels as normal, this is termed myalgia. Statin-induced myositis is diagnosed in symptomatic patients where the CK levels are < 10 x the upper limit of normal. In rhabdomyolysis, CK levels are >10 times the upper limit of normal. In addition, the urine will appear brown due to the presence of myoglobin. 

Several factors contribute to the risk of rhabdomyolysis, including older age (≥65 years), renal impairment, and uncontrolled hypothyroidism.

Hepatotoxicity is rare, reversible, and dose-dependent. It is characterised by a rise in AST and ALT < 3 times the upper limit of normal and usually occurs in the first three months of treatment. Statins do not need to be stopped at this level. Should transaminases rise > 3 times the upper limit of normal, statin therapy should be temporarily stopped before rechallenging or reducing the dose with closer monitoring. LFTs should be repeated after three months of statin treatment, after dose increases, and at one year. 

There is a recognised link between statin use and new-onset diabetes in 10-12% of patients. The mechanism is thought to involve insulin resistance and insulin secretion, and the main risk factors identified were age ≥60 years, rosuvastatin therapy, higher doses, and longer duration of statin therapy.

Lipid regulating medications

Table 4 shows commonly used medications for hyperlipidaemia, and Table 5 summarises additional lipid-regulating medications.

Table 4: Medications for hyperlipidaemia

Table 5: Additional lipid-regulating drugs

Bempedoic acid is a new non-statin drug taken orally in combination with ezetimibe in patients with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidaemia. NICE recommends this as an adjunct to diet in adults where statins are contraindicated or not tolerated or, where ezetimibe alone has failed to control LDL cholesterol. 

Inclisiran, a PCSK-9 inhibitor, can be given as an injection bi-annually to lower LDL cholesterol. NICE recommends this as an option for treating primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidaemia as an adjunct to diet in adults where LDL cholesterol concentrations are persistently >2.6 mmol/ L despite maximum tolerated lipid-lowering therapy and if the patient has any of the following CVD risk factors: 

• ACS
• CAD/PAD
• Coronary or other arterial revascularisation procedures 
• Ischaemic stroke

References

• Calculation of cardiovascular risk in type 1 and 2 diabetes. Available at: https://primarycarenotebook.com/simplepage.cfm?ID=x20150114153930862850.
• Inclisiran for treating primary hypercholesterolaemia. Available at: https://www.nice.org.uk/guidance/ta733/resources/resource-impact-summary-report-9259730749.
• NICE recommendations on use of statins for prevention of CVD. 
• Available https://www.nice.org.uk/News/Article/nice-recommends-wider-use-of-statins-for-prevention-of-cvd
• Shattat, G.F., 2015. A review article on Hyperlipidemia: Types, treatments and new drug targets. Biomedical and Pharmacology Journal. Available at: https://biomedpharmajournal.org/vol7no2/a-review-article-on-hyperlipidemia-types-treatments-and-new-drug-targets/