From the Guidelines
Repatha (evolocumab) does not typically cause hypertriglyceridemia; in fact, it may slightly reduce triglyceride levels in some patients. Repatha is a PCSK9 inhibitor primarily designed to lower LDL cholesterol by increasing the liver's ability to remove LDL from the bloodstream. While its main effect is on LDL cholesterol, clinical studies, such as the FOURIER trial 1, have shown that Repatha can modestly decrease triglyceride levels. The FOURIER trial demonstrated a 16.2% decrease in triglyceride levels with evolocumab compared to a 0.3% increase with placebo. If a patient taking Repatha experiences elevated triglycerides, other factors are likely responsible, such as diet (high carbohydrate or alcohol intake), obesity, uncontrolled diabetes, certain medications (like estrogens, corticosteroids, or beta-blockers), or genetic predisposition. Any significant increase in triglycerides while on Repatha should prompt evaluation of these alternative causes rather than attributing the effect to the medication itself. Patients concerned about triglyceride levels should discuss their complete lipid profile with their healthcare provider.
Some key points to consider when evaluating triglyceride levels in patients taking Repatha include:
- Dietary counseling and weight loss in patients who are overweight or obese, as recommended by the Endocrine Society 1
- Reduced intake of dietary fat and simple carbohydrates in combination with drug treatment to reduce the risk of pancreatitis in patients with severe to very severe hypertriglyceridemia
- Consideration of fibrates, niacin, and n-3 fatty acids, alone or in combination, in patients with moderate to severe hypertriglyceridemia
- Statins may have a modest triglyceride-lowering effect, but should not be used alone in patients with severe or very severe hypertriglyceridemia.
Overall, Repatha is not typically associated with hypertriglyceridemia, and any increases in triglyceride levels should be evaluated in the context of other potential causes.
From the Research
Repatha and Hypertriglyceridemia
- There is no direct evidence in the provided studies that Repatha (evolocumab) causes hypertriglyceridemia 2, 3, 4, 5, 6.
- The studies focus on the efficacy and safety of evolocumab in reducing low-density lipoprotein cholesterol (LDL-C) levels and its effects on cardiovascular outcomes.
- Some studies mention the effects of evolocumab on other lipid parameters, including triglycerides, but do not suggest that it causes hypertriglyceridemia 4, 6.
- In fact, one study notes that treatment with evolocumab significantly improves levels of triglycerides, among other lipid parameters 6.
Mechanism of Action
- Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), leading to a reduction in LDL-C levels 3, 4, 6.
- The mechanism of action of evolocumab does not suggest that it would cause an increase in triglyceride levels.