Goal Triglyceride Levels in ASCVD
For adults with established atherosclerotic cardiovascular disease (ASCVD), the recommended fasting triglyceride goal is <150 mg/dL, with a secondary target of non-HDL cholesterol <130 mg/dL when triglycerides are 200-499 mg/dL. 1
Primary Triglyceride Targets
Optimal fasting triglyceride level: <100 mg/dL – Observational studies and clinical trials consistently demonstrate the lowest risk of incident and recurrent cardiovascular disease at this level, though this represents a physiological parameter of cardiometabolic health rather than a formal therapeutic target. 1
Standard therapeutic goal: <150 mg/dL – This is the widely accepted upper limit of normal range and the primary target for reducing cardiovascular risk in patients with ASCVD. 1, 2
Minimum acceptable level: <200 mg/dL – When triglycerides remain 200-499 mg/dL despite statin therapy, this becomes the threshold for considering additional triglyceride-lowering interventions. 1
Secondary Lipid Targets in ASCVD Patients
Non-HDL cholesterol <130 mg/dL – This secondary target reflects the total atherogenic lipoprotein burden (LDL + VLDL + IDL + Lp(a)) and becomes particularly important when triglycerides are elevated. 1, 3
LDL cholesterol <70 mg/dL – For patients with clinical ASCVD who are judged to be very high risk, this remains the primary cholesterol target even when addressing triglycerides. 1
Treatment Algorithm Based on Triglyceride Levels
Triglycerides 150-199 mg/dL (Mild Elevation)
Continue maximally tolerated statin therapy as the foundation of ASCVD risk reduction, which provides 10-30% dose-dependent triglyceride lowering in addition to proven cardiovascular mortality benefit. 1, 4
Intensify lifestyle modifications: target 5-10% weight loss (produces ~20% triglyceride reduction), restrict added sugars to <6% of total calories, limit total fat to 30-35% of calories, and engage in ≥150 minutes/week of moderate-intensity aerobic activity. 1, 3
Triglycerides 200-499 mg/dL (Moderate Elevation)
Maintain high-intensity statin therapy and optimize lifestyle interventions for at least 3 months before adding non-statin agents. 1
Add icosapent ethyl 2g twice daily if triglycerides remain ≥150 mg/dL after 3 months on maximally tolerated statin therapy, as this is the only triglyceride-lowering agent FDA-approved for cardiovascular risk reduction, demonstrating a 25% reduction in major adverse cardiovascular events (NNT=21). 1, 3
Monitor for increased atrial fibrillation risk (3.1% vs 2.1% with placebo) when prescribing prescription omega-3 fatty acids at 2-4g daily. 1, 3
Triglycerides ≥500 mg/dL (Severe Elevation)
Initiate fenofibrate 54-160 mg daily immediately as first-line therapy to prevent acute pancreatitis (14% risk at this level), regardless of LDL-C or overall cardiovascular risk. 1, 3
Once triglycerides fall below 500 mg/dL with fenofibrate, reassess LDL-C and add or optimize statin therapy if LDL-C is elevated or cardiovascular risk remains high. 1
Evidence Supporting Triglyceride Goals
The PROVE IT-TIMI 22 trial demonstrated that on-treatment triglyceride levels <150 mg/dL were independently associated with lower risk of recurrent coronary heart disease events compared with triglyceride levels ≥150 mg/dL (HR: 0.73; 95% CI: 0.62-0.87; P<0.001) in univariate analysis and (HR: 0.80; 95% CI: 0.66-0.97; P=0.025) in adjusted analysis. 1
Persistently elevated nonfasting triglycerides ≥175 mg/dL are classified as a cardiovascular risk-enhancing factor that should inform treatment intensity decisions in ASCVD patients. 1
The 25% rise in triglyceride levels in US adults during recent decades, coinciding with higher caloric intake and obesity rates, underscores the importance of aggressive triglyceride management to preserve cardiovascular risk reduction gains. 1
Critical Pitfalls to Avoid
Do not delay statin optimization while attempting lifestyle modifications alone in ASCVD patients; both should proceed concurrently as statins provide the strongest evidence for reducing cardiovascular events and mortality. 1, 3
Do not use fibrates as first-line therapy for moderate hypertriglyceridemia (200-499 mg/dL) in ASCVD patients; statins remain first-line, with fibrates reserved for triglycerides ≥500 mg/dL to prevent pancreatitis. 1, 4
Do not overlook secondary causes of hypertriglyceridemia (uncontrolled diabetes, hypothyroidism, excessive alcohol, certain medications); addressing these can lower triglycerides by 20-50% independent of lipid-lowering drugs. 1, 3
Do not combine gemfibrozil with statins due to significantly higher myopathy risk; fenofibrate has a markedly better safety profile when combined with statins because it does not inhibit statin glucuronidation. 1, 3