Dyslipidemia Management
ASCVD Risk Assessment & Statin Initiation
All adults aged 40–75 years with diabetes require at least moderate-intensity statin therapy regardless of baseline LDL-C level or calculated 10-year ASCVD risk (Class I, Level A). 1, 2 This is a mandatory recommendation, not a consideration—diabetes itself is sufficient indication for statin therapy in this age group.
Risk Stratification for Non-Diabetic Adults
- Calculate 10-year ASCVD risk using the Pooled Cohort Equations for all adults aged 40–75 years without diabetes or established ASCVD 1, 2
- 10-year ASCVD risk ≥20%: Initiate high-intensity statin immediately (atorvastatin 40–80 mg or rosuvastatin 20–40 mg daily) to achieve ≥50% LDL-C reduction 1, 2
- 10-year ASCVD risk 7.5–<20%: Start moderate-to-high-intensity statin; upgrade to high-intensity if risk-enhancing factors present (family history of premature CHD, chronic kidney disease, metabolic syndrome, triglycerides ≥175 mg/dL, inflammatory disease) 1, 2
- 10-year ASCVD risk 5–<7.5%: Consider moderate-intensity statin only if risk-enhancing factors exist; coronary artery calcium score ≥100 or ≥75th percentile may justify initiation 1, 2
- 10-year ASCVD risk <5%: Lifestyle modifications alone; pharmacotherapy generally not indicated 1, 2
Severe Primary Hypercholesterolemia
For LDL-C ≥190 mg/dL (≥4.9 mmol/L) in adults aged 20–75 years, initiate high-intensity statin immediately without calculating 10-year ASCVD risk. 1, 2 This threshold mandates treatment regardless of age or other risk factors. Target ≥50% LDL-C reduction from baseline. 1, 2
Secondary Prevention (Established ASCVD)
All patients with clinical ASCVD—regardless of age—require high-intensity statin therapy (atorvastatin 40–80 mg or rosuvastatin 20–40 mg daily). 1, 2 Target LDL-C <70 mg/dL and ≥50% reduction from baseline. 1, 2 If high-intensity statin is not tolerated, maintain the maximum tolerated dose rather than discontinuing therapy. 1, 2
Lifestyle Modifications (Foundation for All Patients)
Lifestyle interventions must be implemented concurrently with pharmacotherapy in high-risk patients—do not delay statin initiation while pursuing lifestyle changes alone. 2
Dietary Pattern
- Adopt Mediterranean or DASH dietary pattern emphasizing vegetables, fruits, whole grains, legumes, low-fat protein, and non-tropical vegetable oils 1, 2
- Limit saturated fat to <7% of total calories; eliminate trans fats completely 1, 2
- Restrict dietary cholesterol to <200 mg/day 2
- Increase viscous fiber to ≥10–25 g/day from oats, beans, lentils, vegetables 2
- Add plant stanols/sterols ≈2 g/day 2
- Consume ≥2 servings/week of fatty fish (salmon, trout, sardines, mackerel) for omega-3 fatty acids 2
Physical Activity
- Perform ≥150 minutes/week of moderate-intensity aerobic activity (or ≥75 minutes/week vigorous-intensity) 1, 2
- Add resistance training: 3 sets of 8–12 repetitions at 60–80% of 1-repetition maximum weight at least 2×/week 1
Weight Management & Tobacco Cessation
- Pursue weight loss when overweight or obese; 5–10% body weight reduction produces ≈20% decrease in triglycerides 1, 2
- Provide smoking cessation counseling plus nicotine replacement, varenicline, and/or bupropion (individually or in combination) 1
Statin Therapy: Intensity Definitions & Dosing
High-Intensity Statins (≥50% LDL-C Reduction)
Moderate-Intensity Statins (30–49% LDL-C Reduction)
- Atorvastatin 10–20 mg daily 1, 2
- Rosuvastatin 5–10 mg daily 1, 2
- Simvastatin 20–40 mg daily 1, 2
- Pravastatin 40–80 mg daily 1, 2
Low-intensity statins are not recommended for any diabetic patient at any age. 2
Non-Statin Add-On Therapies
Ezetimibe (First-Line Add-On)
Add ezetimibe 10 mg daily when LDL-C remains ≥70 mg/dL on maximally tolerated statin in the following populations:
- Diabetic patients aged 40–75 years at higher cardiovascular risk 1, 2
- Patients with established ASCVD (very high risk) 1, 2
- Patients with 10-year ASCVD risk ≥20% who achieve <50% LDL-C reduction on maximally tolerated statin 1, 2
Ezetimibe provides an additional 15–25% LDL-C reduction and has proven cardiovascular benefit when combined with statins. 2, 3, 4 It is preferred over PCSK9 inhibitors due to lower cost when both are options. 2
PCSK9 Inhibitors (Second-Line Add-On)
Add a PCSK9 inhibitor (evolocumab or alirocumab) when LDL-C ≥70 mg/dL despite maximally tolerated statin + ezetimibe in:
- Very high-risk patients with established ASCVD 1, 2, 5
- Diabetic patients aged 40–75 years with multiple ASCVD risk factors 1, 2
- Patients aged 30–75 years with heterozygous familial hypercholesterolemia and LDL-C ≥100 mg/dL on maximally tolerated statin + ezetimibe 1
PCSK9 inhibitors reduce LDL-C by 50–60% above statin therapy alone and reduce cardiovascular events and all-cause mortality in patients with clinical ASCVD. 3, 5 However, they carry uncertain value at mid-2018 U.S. list prices for primary prevention in familial hypercholesterolemia without established ASCVD. 1
Bempedoic Acid (Statin-Intolerant Patients)
For statin-intolerant diabetic patients, use bempedoic acid as an alternative cholesterol-lowering agent to reduce cardiovascular events. 2 PCSK9-inhibitor monoclonal antibodies or inclisiran siRNA may also be considered in statin-intolerant individuals. 2
Management of Elevated Triglycerides
Classification & Risk Thresholds
- Normal: <150 mg/dL 6
- Mild: 150–199 mg/dL 6
- Moderate: 200–499 mg/dL 6
- Severe: 500–999 mg/dL 6
- Very severe: ≥1,000 mg/dL 6
Persistently elevated nonfasting triglycerides ≥175 mg/dL constitute a cardiovascular risk-enhancing factor that should influence treatment decisions. 2, 7
Lifestyle Interventions for Hypertriglyceridemia
- Weight loss: 5–10% body weight reduction produces ≈20% decrease in triglycerides; in some patients, weight loss can reduce triglycerides by up to 70% 6
- Dietary sugar restriction: Limit added sugars to <6% of total calories for mild-to-moderate hypertriglyceridemia; eliminate completely for severe/very severe hypertriglyceridemia 6
- Dietary fat modification: Restrict total fat to 30–35% of calories for moderate hypertriglyceridemia; 20–25% for severe; 10–15% for very severe 6
- Alcohol: Limit or completely avoid; even 1 oz daily increases triglycerides by 5–10% 6
- Physical activity: ≥150 minutes/week moderate-intensity or ≥75 minutes/week vigorous-intensity reduces triglycerides by ≈11% 6
Pharmacologic Therapy for Hypertriglyceridemia
Severe to Very Severe Hypertriglyceridemia (≥500 mg/dL)
Initiate fenofibrate 54–160 mg daily immediately as first-line therapy to prevent acute pancreatitis, regardless of LDL-C levels or cardiovascular risk. 6 Fenofibrate reduces triglycerides by 30–50%. 6 Do not start with statin monotherapy when triglycerides ≥500 mg/dL—statins provide only 10–30% triglyceride reduction and are insufficient for preventing pancreatitis at this level. 6
Moderate Hypertriglyceridemia (200–499 mg/dL)
- If 10-year ASCVD risk ≥7.5% or diabetes present: Initiate moderate-to-high-intensity statin as first-line, which provides 10–30% dose-dependent triglyceride reduction plus proven cardiovascular benefit 6
- If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle + statin therapy: Add prescription omega-3 fatty acids (icosapent ethyl 2–4 g/day) for patients with established cardiovascular disease OR diabetes with ≥2 additional risk factors 6
- Alternative: Add fenofibrate 54–160 mg daily if icosapent ethyl criteria not met 6
Icosapent ethyl is the only triglyceride-lowering therapy FDA-approved for cardiovascular risk reduction, demonstrating a 25% reduction in major adverse cardiovascular events (NNT=21). 6 Monitor for increased risk of atrial fibrillation (3.1% vs 2.1% with placebo). 6
Combination Therapy Safety
When combining fenofibrate with statins, use fenofibrate (NOT gemfibrozil) and consider lower statin doses to minimize myopathy risk, particularly in patients >65 years or with renal disease. 6 Fenofibrate has a significantly better safety profile than gemfibrozil when combined with statins because it does not inhibit statin glucuronidation. 6
Monitoring Strategy
- Obtain fasting lipid panel (total cholesterol, LDL-C, HDL-C, triglycerides) at diagnosis, before starting therapy, and repeat annually while on treatment 2
- Re-measure lipid panel 4–12 weeks after initiating or changing any statin or lipid-lowering therapy to verify response and adherence 1, 2
- In adults <40 years not receiving lipid-lowering drugs, repeat lipid panel at least every 5 years or sooner if new risk factors appear 2
Special Populations
Age >75 Years
- Already on statin therapy: Continue current statin if well-tolerated 1, 2
- Statin-naïve: Consider moderate-intensity statin after shared decision-making, weighing expected longevity, frailty status, polypharmacy burden, and individual goals of care 2
- With established ASCVD: High-intensity statin is mandatory regardless of age 2
Do not discontinue statins based solely on age—cardiovascular benefits persist and absolute risk reduction is actually greater in older adults due to higher baseline risk. 2
Pregnancy
Statin therapy is contraindicated. 2
Chronic Kidney Disease (Non-Dialysis)
Apply the same age- and risk-based statin criteria as the general population. 2 Dose adjustment is not required for atorvastatin; rosuvastatin requires adjustment only when creatinine clearance <30 mL/min/1.73 m². 2
Maintenance Hemodialysis
Do not initiate statin therapy, but continue any statin the patient was already receiving at the time dialysis starts. 2
Critical Pitfalls to Avoid
- Do not withhold statin therapy based solely on age—older adults gain greater absolute benefit due to higher baseline risk 2
- Do not use low-intensity statins in diabetic patients—not recommended at any age 2
- Do not calculate 10-year ASCVD risk for patients with LDL-C ≥190 mg/dL—they require immediate high-intensity therapy 2
- Do not fail to initiate statins in all diabetic adults aged 40–75 years—this is a Class I, Level A recommendation with documented 9% reduction in all-cause mortality and 13% reduction in vascular mortality per 39 mg/dL LDL-C reduction 2
- Do not base statin intensity in diabetic patients aged 40–75 years solely on baseline LDL-C—incorporate the presence of additional ASCVD risk factors 2
- Do not discontinue statins because of intolerance without first trying alternative statins, lower doses, or intermittent dosing schedules 2
- Do not delay statin initiation while attempting lifestyle modifications alone in high-risk patients—pharmacotherapy and lifestyle optimization should occur simultaneously 2