Primary Treatment for Hyperlipidemia
Statins are the first-line pharmacologic treatment for hyperlipidemia, with LDL-cholesterol as the primary target for therapy. 1
Risk Stratification and Treatment Goals
Before initiating therapy, cardiovascular risk must be stratified to determine appropriate LDL-C targets:
- Very high-risk patients (documented CVD, diabetes with target organ damage, severe CKD, or familial hypercholesterolemia): LDL-C goal <1.8 mmol/L (70 mg/dL), or ≥50% reduction if baseline is 1.8-3.5 mmol/L 1
- High-risk patients (diabetes without complications, moderate CKD, or 10-year CHD risk ≥10%): LDL-C goal <2.6 mmol/L (100 mg/dL), or ≥50% reduction if baseline is 2.6-5.2 mmol/L 1
- Moderate-risk patients: LDL-C goal <3.4 mmol/L (130 mg/dL) 1
First-Line Statin Therapy
Initiate statin therapy at doses proven effective in clinical trials rather than starting low and titrating. 2
Statin Selection and Dosing
High-intensity statins should be used for very high-risk patients:
- Atorvastatin 40-80 mg daily reduces LDL-C by 45-61% and has proven efficacy in acute coronary syndromes (PROVE-IT), stable CAD (TNT), and stroke prevention (SPARCL) 2, 3
- Simvastatin 40 mg daily reduces LDL-C by 35-42% and is comparable to atorvastatin 20 mg 4
- For patients with diabetes, statins reduce cardiovascular mortality regardless of baseline LDL-C, with simvastatin and pravastatin having specific trial evidence (4S, CARE) 1
Critical caveat: High-dose statins should be initiated early in acute coronary syndrome patients regardless of initial LDL-C values. 1
Lifestyle Modifications (Concurrent with Pharmacotherapy)
Therapeutic lifestyle changes must be implemented alongside statin therapy, not as a prolonged trial before medication:
- Reduce saturated fat to <7% of calories, dietary cholesterol <200 mg/day 1
- Add plant stanols/sterols (2 g/day) and viscous fiber (10-25 g/day) for additional LDL-C lowering 1
- Achieve ≥30 minutes moderate-intensity physical activity on most days 1
- Weight reduction if BMI ≥25 kg/m² 1
Combination Therapy for Inadequate Response
If LDL-C goal is not achieved after 4-6 weeks on maximally tolerated statin:
For Elevated LDL-C Alone
Add ezetimibe 10 mg daily, which provides an additional 15-25% LDL-C reduction when combined with statins. 5 This combination is preferred over bile acid sequestrants due to better tolerability. 1
For Combined Hyperlipidemia (Elevated LDL-C and Triglycerides)
The treatment algorithm depends on triglyceride levels:
- Triglycerides 150-499 mg/dL with LDL-C not at goal: Intensify statin therapy first; if triglycerides remain >200 mg/dL after 4-6 weeks, add fenofibrate (preferred over gemfibrozil when combining with statins due to lower myopathy risk) 6
- Triglycerides ≥500 mg/dL: Add fibrate therapy immediately to prevent pancreatitis risk, with fenofibrate preferred in combination with statins 6
- Triglycerides ≥1500 mg/dL: Gemfibrozil 600 mg twice daily becomes first-line treatment (can reduce triglycerides by 44-54%), with statin added after triglycerides are controlled 7
Important warning: Never combine gemfibrozil with statins due to significantly increased myopathy risk; use fenofibrate if combination therapy is needed. 7, 6
Special Populations
Diabetes Mellitus
- All type 2 diabetic patients >40 years with any additional risk factor should receive statin therapy targeting LDL-C <1.8 mmol/L (70 mg/dL) 1
- Improved glycemic control is the initial therapy for hypertriglyceridemia in diabetes before adding fibrates 1
Familial Hypercholesterolemia
- Suspect FH when: LDL-C >5 mmol/L (190 mg/dL) in adults, premature CHD (men <55, women <60 years), or tendon xanthomas 1
- Treat with high-intensity statin plus ezetimibe as initial therapy 1
- Consider PCSK9 inhibitors or LDL apheresis if goals not achieved 1
Acute Coronary Syndrome
Initiate high-dose statin (atorvastatin 80 mg) immediately upon admission, regardless of baseline lipid levels. 1 This is a Class I, Level A recommendation that should never be delayed.