Management of raised triglycerides

Referral to secondary care (or seek specialist advice) if triglycerides > =10 mmol/l

• urgent referral (or urgent specialist advice) is indicated if > 20 mmol/l
  
  
• secondary causes (e.g. high alcohol, uncontrolled diabetes, drugs such as isotretinoin) should be identified and treated appropriately together with a reduction in alcohol and a low total fat diet. For more details regarding secondary causes then see linked item
  • effective triglyceride lowering therapies include:
    • high doses of marine omega 3 fatty acids such as Omacor 4 capsules/day or Maxepa 10 capsules/day are effective in severe hypertriglyceridaemia or a fibrate (2)
  • in lipoprotein lipase deficiency pharmacological interventions are ineffective and a strict low total fat diet is required which can be supplemented with medium chain triglycerides.This requires expert dietetic advice
    
    
  • a concensus guidance of hypertriglyceridaemia has been developed (1)
    • for any patient with increased levels of triglycerides, the following laboratory investigations should be ordered:
      • urine dipstick test (protein could indicate nephrotic syndrome; glucose could indicate diabetes)
      • repeat fasting lipid profile, fasting blood glucose, liver function tests, renal function tests, thyroid function tests
      • creatine kinase (especially if you are considering prescribing a fibrate with or without a statin)
      • note that high levels of triglycerides can lead to a falsely low sodium measurement
        
        
    • if raised cholesterol and raised triglyceride (combined hyperlipidaemia)
      • approach to management can be stratified according to the extent of hypertriglyceridaemia:
        • different guidelines state different levels when a patient should be referred for specialist advice:
          • a concensus guideline concerning reducing the risk of cardiovascular disease and pancreatitis (1) states:
            • patients with levels up to 20 mmol/l initially can be managed within primary care
            • patients with levels higher than 20 mmol/l immediately require more specialist care due to the high risk of acute pancreatitis
            • refer for urgent specialist review if a person has a triglyceride concentration of more than 20 mmol/litre that is not a result of excess alcohol or poor glycaemic control (7)
          • a guideline relating to management of raised triglycerides in type 2 diabetes (4) states:
            • because of the significant risk of pancreatitis, those with type 2 diabetes and triglyceride (TG) levels >=10 mmol/l should be considered for referral to a specialist lipid clinic
          • a fasting triglyceride level of >= 10 mmol/L is a reasonable level at which to prompt referral or seeking of specialist advice (2,4)
            
            
      • physicians should aim ideally for a fasting triglyceride level <1.7 mmol/l, but even modest reductions can be considered to reduce the patient's risk of pancreatitis
      • for patients with raised triglyceride levels then management in primary care is appropriate if levels up to 10 mmol/l (2,4):
        • prescribe a statin for example, atorvastatin 20mg, unless there are potential drug interactions or contraindications (Note that statins do reduce triglyceride levels)
          • if triglyceride levels have improved after 8 weeks:
            • continue statin
            • reinforce control of secondary causes and lifestyle changes
          • if triglyceride levels remain >5.6 mmol/l after a statin alone (1):
            • add in omega-3-acid ethyl esters (1 g twice daily increasing to 2 g twice daily if inadequate effect) for 8 weeks (or consider a fibrate for vegetarians or other patients who cannot take fish-derived products):
              • if triglyceride levels improve, continue statins and reinforce control of secondary causes and lifestyle changes
              • if triglyceride levels remain >5.6 mmol/l after a statin plus omega-3-acid ethyl esters, the options include referral or addition of a fibrate (where not already taking) or nicotinic acid, while continuing to reinforce control of secondary causes and lifestyle changes
              • refer to a specialist if triglycerides >10 mmol/l
                
                
      • note that occasionally in combined hyperlipidaemia, a clinician will consider the risk of pancreatitis high (for example if no obvious secondary causes of raised triglyceride or if the cause of raised triglyceride is not easily resolvable (e.g. poor glycaemic control in diabetes)) if the triglyceride 10-20mmol/l and combination therapy with a statin plus a fish oil (or fibrate) may be initial pharmacological management rather than statin alone. In this situation then specialist advice should be sought (2)
        
        
    • if isolated raised triglyceride
      • patients with triglycerides up to 10 mmol/l:
        • initiate omega-3-acid ethyl esters (1 g twice daily increasing to 2 g twice daily if inadequate effect) for 8 weeks and/or fibrate for 8 weeks
          • if triglyceride levels improve:
            • continue omega-3-acid ethyl esters and/or fibrate
            • reinforce control of secondary causes and lifestyle changes
          • if triglyceride levels remain >5.6 mmol/l, the options include referral or replacing the fibrate with modified-release nicotinic acid; continue to reinforce control of secondary causes and lifestyle changes
          • if triglycerides above 10 mmol/l then refer for specialist review
            
            
    • guidance notes:
      • if you are concerned about prescribing the combination of a statin plus a fibrate, consult your lipid clinic for advice
      • always measure creatine kinase and order liver function tests before initiating a fibrate and repeat after 8 weeks
      • in patients with diabetes, nicotinic acid preparations may slightly increase levels of glycosylated haemoglobin (HbA1c) and glucose
        
        
  • in patients at high CVD risk with mixed lipaemia or in patients with familial combined hyperlipidaemia (FCH), statins are first line as they are highly effective in reducing remnant particles as well as LDL (3)
    • often, higher statin doses are needed to achieve treatment goals in patients with FCH than in patients with isolated hypercholesterolaemia
    • diet and lifestyle measures may need to be intensified and statin dose increased. Ezetimibe is a useful addition if statin alone is insufficient
    • combination drug therapy with the addition of a fibrate or nicotinic acid derivative may be required - combination therapy is generally initiated after specialist review/advice
      • treatment also leads to an increase in HDL cholesterol.However, only surrogate evidence of benefit (eg carotid intima-medial thickness, coronary angiography) is available for combination therapy and careful safety monitoring is important
      • patients should be advised to stop their medication in the event of severe generalised muscle pain and tenderness
      • gemfibrozil increases statin levels so this fibrate is best avoided in combination with statins
  • in patients with type 3 hyperlipidaemia, fibrates are often the initial treatment of choice (2)

Notes:

• in patients with a combined hyperlipidaemia where the fasting triglyceride level is significantly raised (different sources suggest this level as either > 8mmol/l or > 10 mmol/l)
  • then the first treatment target is the raised triglyceride because of associated risk of acute pancreatitis
• in the FIELD study there was actually an increased incidence of pancreatitis in the fibrate group compared to the placebo group (5)

Reference:

• (1) Nair et al (June 2010). Consensus guideline on reducing cardiovascular events and pancreatitis through the effective management of triglycerides. Eguidelines
• (2) Editorial comment (July 2010). Dr Jim McMorran, GP with Specialist Interest in Diabetes and Lipids, Coventry and Rugby CCG; Editor GPnotebook.
• (3) British Heart Foundation Factfile (June 2008). Triglycerides.
• (4) Sinclair A et al. Management of elevated serum triglycerides in type 2 diabetes: A pragmatic approach Diabetes & Primary Care, 2012, Vol 14, No 4, pages 223-234.
• (5) Keech A et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005 Nov 26;366(9500):1849-61
• (6) MSD (letter to UK Health Professionals, 21/1/2013). Treatment with Tredaptive should be discontinued.
• (7) NICE (May 2014).Lipid modification - Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease