What is the first line of treatment for hyperlipidemia?

First-Line Treatment for Hyperlipidemia

The first-line treatment for hyperlipidemia is therapeutic lifestyle changes, including diet modification, physical activity, and weight management, followed by statin therapy if lifestyle modifications are insufficient to reach target lipid goals. 1, 2, 3

Initial Assessment and Treatment Approach

• Assess baseline lipid profile (LDL-C, HDL-C, triglycerides) to determine severity and type of hyperlipidemia 2
• Evaluate for secondary causes of hyperlipidemia (thyroid disease, liver disease, renal disease, alcohol use) before initiating therapy 2
• Screen for other cardiovascular risk factors including diabetes, hypertension, obesity, smoking, and family history 4

Therapeutic Lifestyle Changes (First-Line)

Dietary Modifications

• Limit calories from saturated fat to <7% of total calories 1, 2
• Reduce dietary cholesterol to <200 mg/day 1
• Avoid trans-fatty acids completely 2
• Consider adding plant stanols/sterols (up to 2 g/day) for additional LDL-C lowering 1
• Increase viscous (soluble) fiber intake (10-25 g/day) 1
• For elevated triglycerides, decrease simple sugar intake and increase dietary n-3 fatty acids 2
• Emphasize consumption of fruits, vegetables, whole grains, low-fat dairy products, fish, legumes, poultry, and lean meats 1, 2

Physical Activity

• Aim for at least 30 minutes of moderate-intensity physical activity on most days of the week 1, 2
• Include resistance training with 8-10 different exercises, 1-2 sets per exercise, 10-15 repetitions at moderate intensity 2 days/week 1
• Incorporate flexibility training and increased daily lifestyle activities 2

Weight Management

• For overweight or obese patients, weight reduction is essential, particularly for lowering triglycerides 4, 5
• Weight loss is more effective in lowering plasma triglycerides and raising HDL cholesterol than in lowering LDL cholesterol 5

Pharmacological Therapy (When Lifestyle Changes Are Insufficient)

Statins (First-Line Pharmacological Therapy)

• Statins are the first-line pharmacological therapy for LDL-C reduction 1, 2
• They significantly reduce coronary and cerebrovascular events by approximately 30% 1
• High-potency statins (atorvastatin, rosuvastatin, pitavastatin) should be used to achieve LDL-C goals 4
• Monitor for adverse effects, including myopathy and rhabdomyolysis, particularly in elderly patients, those with hypothyroidism or renal impairment 2

Treatment Goals

• LDL-C goals vary based on cardiovascular risk:
  • <100 mg/dL (2.6 mmol/L) for most adults 4, 2
  • <70 mg/dL (1.8 mmol/L) for those with clinical ASCVD or other major risk factors 4
  • <55 mg/dL (1.4 mmol/L) for those with clinical ASCVD 4
• Triglyceride goal: <150 mg/dL (1.7 mmol/L) 4
• HDL-C goal: >40 mg/dL (1.15 mmol/L) in men, >50 mg/dL in women 4

Alternative and Adjunctive Therapies (When Statins Are Insufficient or Not Tolerated)

• Ezetimibe: Consider adding to statin therapy when LDL-C goals are not achieved 4
• Bile acid sequestrants: Option for statin-intolerant patients or as adjunctive therapy 1, 2
• PCSK9 inhibitors: For patients not achieving goals with maximally tolerated statins and ezetimibe 4
• Bempedoic acid: Consider for patients not reaching goals on statins 6
• Fibrates (fenofibrate): Primarily for severe hypertriglyceridemia (≥1,000 mg/dL) 7
• Niacin: Most effective for raising HDL-C but may worsen glycemic control in diabetic patients 4, 2

Special Considerations

Diabetes and Hyperlipidemia

• In patients with diabetes, LDL-C goal is <100 mg/dL 4, 2
• Treatment of LDL cholesterol is the first priority for pharmacological therapy 4
• Improved glycemic control is the first priority for triglyceride lowering in diabetic patients 2
• Consider SGLT2 inhibitors or GLP-1 analogues for diabetic patients with cardiac disease 4

Familial Hypercholesterolemia

• Requires more aggressive therapy, often combination therapy 8
• Consider PCSK9 inhibitors as part of first-line treatment for extremely high-risk patients 4

Common Pitfalls and Caveats

• Failure to rule out secondary causes before initiating drug therapy 2
• Inadequate dosing of statins or premature discontinuation due to minor side effects 2
• When using combination therapy with statins and fibrates, the risk of myositis is higher with gemfibrozil than with fenofibrate 2
• Combination of statins with niacin may worsen hyperglycemia in diabetic patients 2
• Statins alone may be insufficient for patients with severe or familial hyperlipidemia 8, 6