What is the management of dyslipidemia?

Management of Dyslipidemia

Manage dyslipidemia using a risk-stratified approach that targets statin dose intensity based on cardiovascular disease (CVD) risk rather than specific LDL-cholesterol goals, combined with lifestyle modifications including Mediterranean-style diet and aerobic exercise. 1

Risk Assessment and Stratification

Assess 10-year CVD risk at baseline using validated risk calculators (adapted from Framingham Heart Study) to determine treatment intensity. 1 The assessment should identify:

• Clinical atherosclerotic CVD (ASCVD): Prior MI, acute coronary syndrome, stroke/TIA, coronary revascularization (PCI/CABG), peripheral vascular disease, or abdominal aortic aneurysm 1
• CVD risk equivalents: Diabetes mellitus, chronic kidney disease, or calculated 10-year CVD risk ≥12% 1
• Moderate risk: 10-year CVD risk 6-12% 1
• Lower risk: 10-year CVD risk <6% 1

Do not recheck lipid levels with each CVD risk assessment, as lipid levels remain stable within patients over time and contribute minimally to predicted risk relative to other factors. 1 Previously measured lipid levels can be reliably used in serial CVD risk assessments. 1

Pharmacologic Treatment Strategy

Secondary Prevention (Established ASCVD)

For patients with clinical ASCVD, initiate moderate-to-high intensity statin therapy without targeting specific LDL-C goals. 1

• High-intensity statins: Atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily 1
• Moderate-intensity statins: Atorvastatin 10-20 mg, simvastatin 20-40 mg, pravastatin 40-80 mg, or lovastatin 40 mg daily 1

For very high-risk secondary prevention patients (recent ACS, recurrent events, or multiple high-risk conditions), consider stepped intensification by adding ezetimibe 10 mg daily to statin therapy. 1, 2 Ezetimibe reduces LDL-C by an additional 15-20% when combined with statins and is indicated when additional LDL-C lowering is needed. 2

Primary Prevention

For patients with diabetes or 10-year CVD risk ≥12%: Initiate moderate-intensity statin therapy 1

For patients with 10-year CVD risk 6-12%: Consider moderate-intensity statin therapy, particularly if additional risk-enhancing factors are present 1

For patients with 10-year CVD risk <6%: Focus on lifestyle modifications; statins generally not indicated unless familial hypercholesterolemia or other high-risk conditions exist 1

Special Populations

Familial hypercholesterolemia (heterozygous): Combine high-intensity statin with ezetimibe as adjunct to diet 2

Familial hypercholesterolemia (homozygous): Combine statin with ezetimibe and consider additional LDL-C lowering therapies 2

Mixed hyperlipidemia (elevated LDL-C and triglycerides with low HDL-C): Consider combination therapy with statin plus fenofibrate, though evidence for cardiovascular benefit is limited 2, 3

Elimination of LDL-C Treatment Targets

The evidence does not support using specific LDL-C or non-HDL-C levels as treatment targets. 1 The 2020 VA/DoD guideline emphasizes that:

• Available trials were not designed as treat-to-target studies 1
• Post-hoc analyses suggesting benefit of specific targets should be considered hypothesis-generating, not proof of benefit 1
• Focus treatment decisions on statin dose intensity appropriate to the patient's CVD risk category rather than titrating to achieve numerical lipid goals 1

This represents a fundamental shift from older approaches and differs from some other guidelines, but is based on the strongest randomized trial evidence prioritizing hard outcomes (CVD mortality, MI, stroke). 1

Lifestyle Modifications

Dietary Interventions

Recommend a Mediterranean-style diet as the primary dietary pattern for CVD risk reduction. 1 This includes:

• Emphasis on vegetables, fruits, whole grains, legumes, nuts
• Olive oil as primary fat source
• Moderate fish and poultry consumption
• Limited red meat and processed foods 1

Weight reduction if overweight or obese through caloric restriction and increased physical activity 1, 3

Physical Activity

Prescribe regular aerobic physical activity: Minimum 150 minutes per week of moderate-intensity exercise or 75 minutes per week of vigorous-intensity exercise. 1 Physical activity provides cardiovascular benefits independent of lipid effects. 1

Tobacco Cessation

Mandate complete tobacco cessation in all patients, as smoking is a major modifiable CVD risk factor. 3, 4

Laboratory Monitoring

Obtain baseline lipid panel before initiating therapy. 1

Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating therapy to confirm medication adherence and response, but not to guide dose titration to specific targets. 2

Monitor liver enzymes (ALT/AST) at baseline and as clinically indicated. 2, 5 Consider withdrawing therapy if transaminase elevations ≥3× upper limit of normal persist. 2

Monitor for muscle symptoms and check creatine kinase if myopathy is suspected. 5 Discontinue statin if rhabdomyolysis is suspected (CK >10× ULN with symptoms). 5

Statin Intolerance

For patients unable to tolerate appropriate moderate- or high-dose statin: Use the highest tolerable statin dose according to their risk category. 1

If complete statin intolerance: Consider ezetimibe monotherapy (10 mg daily) when additional LDL-C lowering therapy is needed but statins cannot be used. 2

Additional Risk Stratification Tests

Do not routinely use additional risk-stratifying tests such as coronary artery calcium scoring, carotid intima-media thickness, ankle-brachial index, or exercise testing for asymptomatic atherosclerosis to guide treatment decisions in most patients. 1 These tests have not been shown to improve cardiovascular outcomes when added to standard risk assessment. 1

Combination Therapy Considerations

When combining ezetimibe with statins: Administer together without regard to timing. 2

When using bile acid sequestrants: Administer ezetimibe ≥2 hours before or ≥4 hours after the bile acid sequestrant to avoid binding interactions. 2

Avoid combining ezetimibe with fibrates other than fenofibrate until use is adequately studied, due to potential safety concerns. 2

Monitor cyclosporine levels closely if coadministering with ezetimibe, as combination increases exposure of both drugs. 2

Common Pitfalls to Avoid

• Do not chase LDL-C numbers: The evidence supports dose-based statin therapy matched to risk, not titration to specific lipid targets 1
• Do not over-test lipids: Frequent lipid monitoring does not improve outcomes and lipid levels remain stable over time 1
• Do not use statins in isolation: Lifestyle modifications (diet, exercise, smoking cessation) are essential components of comprehensive CVD risk reduction 1
• Do not ignore diabetes as a CVD risk equivalent: Diabetic patients warrant statin therapy similar to secondary prevention patients 1
• Do not overlook statin adverse effects: Monitor for hepatotoxicity and myopathy, particularly with high-dose therapy or drug interactions 2, 5