starting statin therapy

Last reviewed 01/2018

• exclude secondary causes of hyperlipidaemia e.g. diabetes, hypothyroidism, liver/renal impairment
• check baseline lipids, liver and renal function, creatine phosphokinase (CK)
• advise patient regarding medication e.g. adverse effects of statin treatment
• start statin treatment - statins should be taken in the evening for maximal effect, and require 4 weeks or more to exert their full effect on lipid concentrations
• LFT should be carried out before and within 4-6 weeks of starting statin therapy (1). Thereafter at intervals of 6 months to 1 year - earlier if clinical features of hepatotoxicity; also at the first review at 4-6 weeks - enquire about adverse effects such as itching, rash, myalgia, arthralgia, insomnia (1)
• if satisfactory lipid control and no evidence of adverse effects then review again at 4-6 months, then 6-12 monthly
• if unsatisfactory lipid control then measurements should be repeated 6 weeks after dosage adjustments are made until the desired lipid concentrations are achieved (2)
• however NICE state that LFTs only need to be measured on three occasions:
  • baseline liver enzymes should be measured before starting a statin. Liver function (transaminases) should be measured within 3 months of starting treatment and at 12 months, but not again unless clinically indicated
  • people who have liver enzymes (transaminases) that are raised but are less than 3 times the upper limit of normal should not be routinely excluded from statin therapy
• treatment should be discontinued if serum transaminase concentrations rise to, and persist at, 3x normal range
• patients must be advised to report any unexpected muscle pain. Statins have been associated with the development of myositis, myopathy and myalgia. Some suggest if there is a marked elevation in creatine kinase concentration (>10 times the upper limit of normal) and a diagnosis of myopathy is suspected then the statin therapy should be stopped; however it has also been suggested that if the creatine kinase level is >5x the upper limit of normal then treatment should be stopped, while the patient is adequately monitored for muscular symptoms and cardiovascular risk (4)

Notes:

• it has been suggested that rather than starting with the lowest licensed dosage, initial dosages of pravastatin (40mg) and simvastatin (20mg) should be used as in published studies (5)
• the Joint British guidelines suggest that it is common practice to measure baseline CK and alanine/aspartate transaminases (ALT or AST) before starting treatment with a statin as some people may have high values that are physiological, not pathological (6)
• after initiating treatment with a statin, CK only needs to be checked again if definite unexplained muscle symptoms are reported (6)
• NICE (7) note that:
  • both total and HDL cholesterol should be measured to achieve the best estimate of CVD risk with Framingham 1991 risk equations
  • before starting lipid modification therapy for primary prevention, people should have at least one fasting lipid sample taken to measure total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides
  • people in whom familial hypercholesterolaemia or other monogenic disorders are suspected because of a combination of clinical findings, lipid profiles and family history of premature CHD should be considered for further investigation and specialist review
  • people with severe hyperlipidaemia should be considered for further investigation and/or specialist review
  • with respect to monitoring:
    • if a person taking a statin starts taking additional drugs, or needs treatment for a concomitant illness that interferes with metabolic pathways or increases the propensity for drug and food interactions, consider reducing the dose of the statin, or temporarily or permanently stopping it
    • people who are being treated with a statin should be advised to seek medical advice if they develop muscle symptoms (pain, tenderness or weakness). If this occurs, creatine kinase should be measured
    • creatine kinase should not be routinely monitored in asymptomatic people who are being treated with a statin - it was noted in the JBS2 guidance that a baseline CK measurement is common practice
    • if a person develops an unexplained peripheral neuropathy, statins should be discontinued and specialist advice sought

Reference:

• (1) Prescriber 2000; 11 (23): 77-85.
• (2) Scottish Intercollegiate Guidelines Network (SIGN). Lipids and primary prevention of coronary heart disease. A National Clinical Guideline. www.sign.ac.uk [September 1999]
• (3) BNF 2.12
• (4) Current Problems in Pharmacovigilance 2002; 28: 8-9.
• (5) Drug and Therapeutics Bulletin 2001; 39 (3): 17-21
• (6) JBS2: Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice. Heart 2005; 91 (Supp 5).
• (7) NICE (May 2008).Lipid modification - Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease