Targeting Triglycerides to Treat Residual CV Risk

Volume 6, Issue 1

Management of hyperlipidemia continues to become more complex as additional agents are approved. Studies have shown that despite the use of statin therapy, atherosclerotic cardiovascular disease (ASCVD) event rates remain high in patients with elevated triglycerides. Elevated triglycerides are associated with an increase in remnant cholesterol, a decrease in high-density lipoprotein cholesterol (HDL-C), and an increase in low-density lipoprotein (LDL) particles with a change in morphology to smaller, more dense particles that are more atherogenic than the lighter, less dense variety.

This past week, the American College of Cardiology and American Heart Association published updated guidelines for the treatment of hypertriglyceridemia, which we will dedicate this week’s issue of Talking Therapeutics to unpacking and exploring.

Point 1: Start with statins for those at highest risk

Although commonly recognized for their impact on LDL-C, statins also provide a 10% to 30% dose-dependent reduction in triglycerides in patients with elevated triglyceride levels. For the highest risk groups, like those with diabetes and established ASCVD, these patients will already be on statin treatment. For these two high-risk groups who have fasting triglycerides ≥150 mg/dL, or nonfasting triglycerides ≥175 mg/dL and triglycerides <500 mg/dL, lifestyle intervention (ie, weight loss and alcohol moderation) is a key first step. If these measures fail, the new guidelines advocate for consideration of icosapent ethyl for those with ASCVD and at least one additional risk factor (eg, aged older than 55 years, current smoker, treated hypertension, etc).

For patients with diabetes but no clinical ASCVD, the guidelines favor intensification of statin therapy when treating persistent hypertriglyceridemia, rather than adding on another medication.

Point 2: Only treat with very high numbers in all the rest

For adults with serum triglycerides >500 mg/dL but without diabetes or clinical ASCVD, the primary focus is on ruling out secondary causes (eg, hypothyroidism, Cushing syndrome), followed by lifestyle optimization (including a very-fat diet for those with triglycerides 1000 mg/dL). When these interventions fail, the guidelines suggest that either a fibrate (fenofibrate preferred) or a prescription omega-3 product (no preferred product). The primary goal for these patients is to prevent pancreatitis, rather than reducing residual ASCVD risk.

Finally, for adults with triglycerides ≥150 mg/dL, or nonfasting triglycerides ≥175 mg/dL and triglycerides <500 mg/dL, the guideline recommend assessment of ASCVD risk and initiating statin therapy for those with a 10-year risk of ≥5%.

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