SUMMARY:

The 2026 ACC/AHA guidelines retire and replace the 2018 ones and specifically address the evaluation, management, and monitoring of individuals with dyslipidemias, including high blood cholesterol, hypertriglyceridemia, and elevated lipoprotein(a). Management of hypertriglyceridemia is a critical element of reducing overall risk of atherosclerotic cardiovascular diseases (ASCVD).

ASCVD Screening Recommendations (adults)

• General population: Begin age 19 years | Screen every 5 years
• Adults with ASCVD risk factors: Screen more frequently than every 5 years

Note: Use the new and improved PREVENT-ASCVD equation (‘Learn More – Primary Sources’ Section Below) to estimate 10-year (and 30-year) risk and to guide therapeutic decisions

Lab Testing

• General population
  • Either a fasting or nonfasting lipid profile is sufficient
  • Only minimal difference in LDL-C between fasting and nonfasting
• Fasting lipid profile indicated
  • Nonfasting lipid profile with triglyceride (TG) level ≥ 400 mg/dL
  • Known/suspected TG metabolism disorder
  • Family history of dyslipidemia or premature ASCVD

Once lipid-lowering therapies are initiated, clinicians should monitor a lipid profile again in 4 to 12 weeks and then every 6 to 12 months thereafter

Primary Prevention

• TG ≥ 150 to 499 mg/dL
  • First line: counsel on lifestyle measures
    • Diet (low in sugars, alcohol, saturated fat)
    • Routine exercise
    • Overweight or obese: body weight loss of 5 to 10%
  • Use non-HDL-C or apoB rather than LDL-C levels to guide therapy
  • Identify and manage secondary causes of hypertriglyceridemia
  • Estimate 10-year ASCVD risk with PREVENT-ASCVD calculator
    • Discuss potential initiation of statin to achieve lipid goals
    • Consider apoB goals
• Persistent severe hypertriglyceridemia (TG ≥ 500 mg/dL)
  • Identify and manage secondary causes of hypertriglyceridemia
  • Optimize lifestyle measures
  • Estimate 10-year risk with PREVENT-ASCVD
  • Maximize statin and other lipid lowering therapy to achieve LDL-C and non-HDL-C goals
  • Consider optional apoB goals
  • Start fibric acid derivative or prescription omega-3 fatty acids
    • Lowers TG level
    • Reduces risk of pancreatitis
• Familial Chylomicronemia Syndrome (FCS) and TG ≥ 1000 mg/dL
  • Refer to a lipid specialist
  • Start fibric acid derivative or prescription omega-3 fatty acids
  • Add olezarsen 80mg monthly

Secondary Prevention

Take a stepwise approach for adults with elevated TG and history of ASCVD

• Identify and manage secondary causes of high TG
• Optimize diet, exercise, ETOH intake and weight management
• Maximize statin and other LDL-lowering therapies to achieve lipid goals
• If needed, add icosapent ethyl to lower TG below 150 mg/dL

TG-Lowering Medications

Fibrates

• Route: oral
• Mechanism: Stimulates PPAR-alpha, which activates increases lipolysis and elimination of TG-rich particles
• First line option for severe hypertriglyceridemia (≥500 mg/dL and especially ≥1000 mg/dL
• Can reduce TG by 30 to 50%
• Agents:
  • Fenofibrate (40 to 200mg daily)
  • Fenofibric acid (35 to 135mg daily)
  • Gemfibrozil (600mg x2 daily)
    • Only fibrate to reduce cardiovascular events in primary and secondary prevention
    • Should not be combined with statin

Omega-3 fatty acids (80mg monthly injection)

• Route: oral
• Mechanism: Reduces hepatic VLDL TG synthesis and/or secretion
• First line option for severe hypertriglyceridemia (≥500 mg/dL)
• Give with a fat-containing meal to ensure absorption
• Reduce TG level by 15 to 61%
• Agents:
  • Icosapent ethyl (4g x2 daily)
    • Reduces cardiovascular events in ASCVD primary prevention with DM2 or in secondary prevention if TG between 150-499 mg/dL and LDL-C is 41 to 100 mg/dL despite statin therapy
  • Omega-3 acid ethyl esters (x1 to 2 daily with food)

Niacin

• Route: oral
• Mechanism: Reduces esterification of hepatic TG, removing TG-rich lipoproteins from fatty acids
• Last line agent for severe hypertriglyceridemia due to side effect profile
• Side effects: insulin resistance | skin flushing | hepatotoxicity
• No reduction in cardiovascular events when added to statin therapy for ASCVD secondary prevention
• Agents:
  • Extended-release niacin (500 to 2000mg daily
    • Reduces TG by 10 to 30%
  • Immediate-release niacin (250 to 6000mg x2 to 3 daily)
    • Reduces TG by 20 to 50%

Olezarsen

• Route: subcutaneous
• Mechanism: Binds to and degrades apoC-III mRNA, reducing apoC-III protein and leading to increased clearance of plasma TG and VLDL
• Only approved for familial chylomicronemia syndrome
• Can reduce TG by 30%

Learn More – Primary Sources

ACC/AHA: Guideline on the Management of Dyslipidemia (2026)

AHA: PREVENT Online Equation for ASCVD Risk Calculation