Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

chylomicronaemia

1st line – hospital admission + supportive care

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ACUTE
|
chylomicronaemia
1st line – 

hospital admission + supportive care

Patients with acute pancreatitis due to chylomicronaemia should be admitted to hospital. They should have intravenous hydration and take nothing by mouth during the acute phase of illness (first 48-72 hours). Plasmapheresis or plasma exchange is generally not necessary because triglyceride (TG) levels will fall with a half-life of 24-30 hours with cessation of oral intake and supportive care alone. Patients should then be transitioned to clear fluids, followed by a low-fat diet with advice for long-term lifestyle modification.

Intravenous insulin infusion in patients with poorly controlled diabetes may help reduce TG levels. See Complications.

Once TG levels are <5 mmol/L (<440 mg/dL), LDL-cholesterol-lowering drugs such as statins can be commenced to achieve non-HDL-cholesterol target goals as recommended according to cardiac risk factor status. The optimal goal is a TG level <1.7 mmol/L (<150 mg/dL), but typically this is not realistic. Fibrate therapy is recommended as prophylaxis against future pancreatitis episodes.[2][9]

ONGOING

moderate HTG (fasting TG ≥1.7 mmol/L [≥150 mg/dL] or non-fasting TG ≥2.0 mmol/L [≥175 mg/dL] and TG <5.6 mmol/L [<500 mg/dL])

1st line – lifestyle and risk factor modifications

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ONGOING
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moderate HTG (fasting TG ≥1.7 mmol/L [≥150 mg/dL] or non-fasting TG ≥2.0 mmol/L [≥175 mg/dL] and TG <5.6 mmol/L [<500 mg/dL])
1st line – 

lifestyle and risk factor modifications

In the US, the American Heart Association/American College of Cardiology (AHA/ACC) guidelines define moderate HTG as fasting or non-fasting triglyceride (TG) 2.0 to 5.6 mmol/L (175-499 mg/dL), and the 2021 ACC expert consensus uses a definition of fasting TG ≥1.7 mmol/L (≥150 mg/dL) or non-fasting TG ≥2.0 mmol/L (≥175 mg/dL) to <5.6 mmol/L (<500 mg/dL).[2][9]

Lifestyle modifications are the first-line intervention for all patients with HTG. Guidelines advise addressing and treating lifestyle factors including overweight/obesity, diet, alcohol, and physical activity.[9][11] Referral to a registered dietitian nutritionist should be considered depending on TG level.

Plus – identify and manage secondary causes

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ONGOING
|
moderate HTG (fasting TG ≥1.7 mmol/L [≥150 mg/dL] or non-fasting TG ≥2.0 mmol/L [≥175 mg/dL] and TG <5.6 mmol/L [<500 mg/dL])
Plus – 

identify and manage secondary causes

Treatment recommended for ALL patients in selected patient group

Secondary causes of HTG may include medical conditions and drugs, as well as lifestyle factors.[4][5][9]

The presence of conditions including diabetes, metabolic syndrome, insulin resistance, obesity, chronic kidney disease, nephrotic syndrome, hypothyroidism, pregnancy (particularly in the third trimester when TG elevation associated with pregnancy is peaking), myeloma, systemic lupus erythematosus, liver disease, HIV infection, Cushing syndrome, or sarcoidosis should be considered.

Drugs that increase TG (e.g., glucocorticoids, anabolic steroids, oral oestrogens, thiazide and loop diuretics, non-cardioselective beta-blockers, isotretinoin, bexarotene, propofol, bile acid sequestrants, cyclophosphamide, asparaginase, capecitabine, interferon, tacrolimus, sirolimus, ciclosporin, protease inhibitors, second-generation antipsychotic agents [e.g., clozapine, olanzapine]) should be discontinued or replaced with metabolically neutral alternatives, if possible.

Consider – statin

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ONGOING
|
moderate HTG (fasting TG ≥1.7 mmol/L [≥150 mg/dL] or non-fasting TG ≥2.0 mmol/L [≥175 mg/dL] and TG <5.6 mmol/L [<500 mg/dL])
Consider – 

statin

Additional treatment recommended for SOME patients in selected patient group

Patients with HTG are treated based on their atherosclerotic cardiovascular disease (ASCVD) risk and LDL-cholesterol levels, primarily using statins as per guidelines. The 2018 AHA/ACC guidelines suggest that if an adult patient with mild-to-moderate HTG has poorly controlled risk factors for ASCVD and a 10-year risk of ASCVD ≥7.5%, it is reasonable to either initiate or intensify statin therapy. For those with a 10-year ASCVD risk 5% to <7.5% and persistent HTG, patient-clinician discussion is recommended regarding the initiation of moderate-intensity statin therapy.[2][9]

Primary options

High-intensity statin

atorvastatin: 40-80 mg orally once daily

OR

High-intensity statin

rosuvastatin: 20-40 mg orally once daily

OR

Moderate-intensity statin

atorvastatin: 10-20 mg orally once daily

OR

Moderate-intensity statin

rosuvastatin: 5-10 mg orally once daily

OR

Moderate-intensity statin

simvastatin: 20-40 mg orally once daily; increased risk of myopathy with 80 mg/day dose

OR

Moderate-intensity statin

pravastatin: 40-80 mg orally once daily

OR

Moderate-intensity statin

lovastatin: 40-80 mg orally (immediate-release) once daily

OR

Moderate-intensity statin

fluvastatin: 40 mg orally (immediate-release) twice daily; 80 mg orally (extended-release) once daily

OR

Moderate-intensity statin

pitavastatin: 1-4 mg orally once daily

Consider – additional LDL-cholesterol-lowering therapy

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ONGOING
|
moderate HTG (fasting TG ≥1.7 mmol/L [≥150 mg/dL] or non-fasting TG ≥2.0 mmol/L [≥175 mg/dL] and TG <5.6 mmol/L [<500 mg/dL])
Consider – 

additional LDL-cholesterol-lowering therapy

Additional treatment recommended for SOME patients in selected patient group

Patients with persistent HTG can be considered for additional non-statin LDL-cholesterol-lowering drugs depending on the LDL-cholesterol level as per guidelines.[2]

US guidelines recommend that those with LDL-cholesterol ≥2.6 mmol/L (≥100 mg/dL) maximise statin therapy and consider additional LDL-cholesterol-guided non-statin therapy before moving to a TG-guided approach (e.g., considering icosapent ethyl).[9] For those with LDL-cholesterol 1.8 to 2.6 mmol/L (70-99 mg/dL) the decision to use LDL-cholesterol-guided non-statin therapy or a TG-guided approach is individualised.

Non-statin LDL-cholesterol-lowering treatments can be added to maximally tolerated statin therapy. Examples include ezetimibe, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (e.g., alirocumab, evolocumab), or bempedoic acid.[60]​ 

Primary options

ezetimibe: 10 mg orally once daily

OR

alirocumab: 75-150 mg subcutaneously every 2 weeks; or 300 mg subcutaneously every 4 weeks

OR

evolocumab: 140 mg subcutaneously every 2 weeks; or 420 mg subcutaneously once monthly

OR

bempedoic acid: 180 mg orally once daily

Consider – icosapent ethyl

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ONGOING
|
moderate HTG (fasting TG ≥1.7 mmol/L [≥150 mg/dL] or non-fasting TG ≥2.0 mmol/L [≥175 mg/dL] and TG <5.6 mmol/L [<500 mg/dL])
Consider – 

icosapent ethyl

Additional treatment recommended for SOME patients in selected patient group

The addition of icosapent ethyl may be considered in patients with persistent TG ≥1.7 mmol/L (≥150 mg/dL) despite maximally tolerated LDL-cholesterol-guided therapy and consideration of lifestyle factors.

Patients with moderate HTG considered for icosapent ethyl in US guidelines include those with ASCVD and either LDL-cholesterol <1.8 mmol/L (<70 mg/dL) or LDL-cholesterol 1.8 to 2.6 mmol/L (70-99 mg/dL), or those age >50 years without ASCVD, but with diabetes and one or more high-risk factors for ASCVD.[9][62]

Primary options

icosapent ethyl: 2 g orally twice daily

severe HTG (fasting TG ≥5.6 mmol/L [≥500 mg/dL] especially fasting TG ≥11.3 mmol/L [≥1000 mg/dL])

1st line – lifestyle and risk factor modifications

Back
ONGOING
|
severe HTG (fasting TG ≥5.6 mmol/L [≥500 mg/dL] especially fasting TG ≥11.3 mmol/L [≥1000 mg/dL])
1st line – 

lifestyle and risk factor modifications

Lifestyle modifications are the first-line intervention for all patients with HTG. Guidelines advise addressing and treating lifestyle factors including overweight/obesity, diet, alcohol, and physical activity.[2][9]

In patients with persistent fasting triglyceride (TG) 5.6 to 11.3 mmol/L (500-999 mg/dL), a low-fat diet should be emphasised, with a very low-fat diet considered in some patients. Alcohol should be avoided. Referral to a registered dietitian nutritionist should be considered.

Plus – identify and manage secondary causes

Back
ONGOING
|
severe HTG (fasting TG ≥5.6 mmol/L [≥500 mg/dL] especially fasting TG ≥11.3 mmol/L [≥1000 mg/dL])
Plus – 

identify and manage secondary causes

Treatment recommended for ALL patients in selected patient group

Secondary causes of HTG may include medical conditions and drugs, as well as lifestyle factors.[4][5][9]

The presence of conditions including diabetes, metabolic syndrome, insulin resistance, obesity, chronic kidney disease, nephrotic syndrome, hypothyroidism, pregnancy (particularly in the third trimester when TG elevation associated with pregnancy is peaking), myeloma, systemic lupus erythematosus, liver disease, HIV infection, Cushing syndrome, or sarcoidosis should be considered.

Drugs that increase TG (e.g., glucocorticoids, anabolic steroids, oral oestrogens, thiazide and loop diuretics, non-cardioselective beta-blockers, isotretinoin, bexarotene, propofol, bile acid sequestrants, cyclophosphamide, asparaginase, capecitabine, interferon, tacrolimus, sirolimus, ciclosporin, protease inhibitors, second-generation antipsychotic agents [e.g., clozapine, olanzapine]) should be discontinued or replaced with metabolically neutral alternatives, if possible.

Consider – statin

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ONGOING
|
severe HTG (fasting TG ≥5.6 mmol/L [≥500 mg/dL] especially fasting TG ≥11.3 mmol/L [≥1000 mg/dL])
Consider – 

statin

Additional treatment recommended for SOME patients in selected patient group

Statin therapy should be considered in appropriate patient groups depending on LDL-cholesterol level and risk as per guidelines.[2][9] 

US guidelines suggest that in an adult patient with TG 5.6 to 11.3 mmol/L (500-999 mg/dL) and a 10-year risk of atherosclerotic cardiovascular disease (ASCVD) ≥5%, ASCVD, or diabetes, it is reasonable to either initiate or intensify statin therapy. For those with TG ≥11.3 mmol/L (≥1000 mg/dL) statin initiation or intensification should be considered.[2][9]

Primary options

High-intensity statin

atorvastatin: 40-80 mg orally once daily

OR

High-intensity statin

rosuvastatin: 20-40 mg orally once daily

OR

Moderate-intensity statin

atorvastatin: 10-20 mg orally once daily

OR

Moderate-intensity statin

rosuvastatin: 5-10 mg orally once daily

OR

Moderate-intensity statin

simvastatin: 20-40 mg orally once daily; increased risk of myopathy with 80 mg/day dose

OR

Moderate-intensity statin

pravastatin: 40-80 mg orally once daily

OR

Moderate-intensity statin

lovastatin: 40-80 mg orally (immediate-release) once daily

OR

Moderate-intensity statin

fluvastatin: 40 mg orally (immediate-release) twice daily; 80 mg orally (extended-release) once daily

OR

Moderate-intensity statin

pitavastatin: 1-4 mg orally once daily

Consider – icosapent ethyl or omega-3 acid ethyl esters

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ONGOING
|
severe HTG (fasting TG ≥5.6 mmol/L [≥500 mg/dL] especially fasting TG ≥11.3 mmol/L [≥1000 mg/dL])
Consider – 

icosapent ethyl or omega-3 acid ethyl esters

Additional treatment recommended for SOME patients in selected patient group

If TG levels are persistently elevated or increasing, US guidelines recommend adding a prescription omega-3 acid (icosapent ethyl or omega-3 acid ethyl esters) to therapy.[2][9]

One European regulatory review found that omega-3 ethyl esters, used in the treatment of hyper triglyceridaemia, are associated with a dose-dependent increased risk of atrial fibrillation.

Primary options

icosapent ethyl: 2 g orally twice daily

OR

omega-3-acid ethyl esters: 4 g/day orally given in 1-2 divided doses

Consider – fibrate

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ONGOING
|
severe HTG (fasting TG ≥5.6 mmol/L [≥500 mg/dL] especially fasting TG ≥11.3 mmol/L [≥1000 mg/dL])
Consider – 

fibrate

Additional treatment recommended for SOME patients in selected patient group

If TG levels are persistently elevated or increasing, US guidelines recommend adding fibrates to therapy to reduce risk of pancreatitis.[2][9]

Gemfibrozil should not be used in combination with a statin. Fenofibrate is the drug of choice if combination treatment is required.

Primary options

fenofibrate micronised: dose depends on brand; consult product literature for guidance on dose

OR

gemfibrozil: 600 mg orally twice daily

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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