SAT-261 Evinacumab as an Effective Treatment Option for Refractory Hypertriglyceridemia

Abstract Disclosure: J.A. Aurora: None. A. Leung: None. K. Nguyen: None. D. DeNofrio: None. L. Keefe: None. R.D. Siegel: None. Background: The goals of hypertriglyceridemia treatment are focused on reducing risk of pancreatitis and atherosclerotic cardiovascular disease (ASCVD). For cases of severe hypertriglyceridemia, effective medications may include statins, fibrates, omega-3 fatty acids, and PCSK9 inhibitors. Evinacumab is an angiopoietin-like 3 inhibitor approved for homozygous familial hypercholesterolemia. In addition, by enhancing VLDL remnant clearance, it can also reduce triglycerides and apolipoprotein B (apoB) levels, an important marker for ASCVD. Patients with cardiac allograft vasculopathy (CAV) are at increased risk of graft failure from accelerated atherosclerosis in the setting of dyslipidemia. We present a case of refractory hypertriglyceridemia and CAV with significant improvement in lipid profile after treatment with evinacumab. Clinical Case: A 61-year-old female with longstanding refractory hypertriglyceridemia, type 2 diabetes mellitus, and orthotopic heart transplantation due to radiation- and anthracycline-induced cardiomyopathy developed CAV after transplantation. Her triglycerides (TGs) were routinely between 2,000-5,000 mg/dL (reference range [RR] < 149 mg/dL), although she had no history of pancreatitis or genetic mutation for dyslipidemia. Despite using atorvastatin 80 mg daily, fenofibrate 162 mg daily, icosapent ethyl 2 g twice daily, and evolocumab 140 mg every 2 weeks, she continued to have hypertriglyceridemia. Given persistent elevation in TGs coupled with her aggressive CAV, evinacumab monthly infusion was added to her regimen. Prior to initiation, TGs were 2,695 mg/dL, direct LDL-C 25 mg/dL (RR < 100 mg/dL), apoB 106 mg/dL (RR < 90 mg/dL), and lipoprotein (a) 12 nmol/L (RR < 75 nmol/L). After a month of evinacumab therapy, there was a dramatic improvement in her TGs to 1,000 mg/dL (62.9% decrease), without a significant change in the rest of her lipid profile. As her CAV was worsening based on a left heart catheterization (LHC) 5 months prior to starting evinacumab, a LHC was repeated 1 month later and revealed no progression in her CAV. Three months after starting evinacumab, there was improvement in her entire lipid profile with sustained improvement in TGs: 1,306 mg/dL (51.5% decrease), direct LDL-C 9 mg/dL (64% decrease), apoB 68 mg/dL (35.8% decrease), and lipoprotein (a) 9.4 nmol/L (21.7% decrease). Conclusion: Evinacumab may be an effective alternative agent for the management of chronic hypertriglyceridemia based on the robust effects seen in our patient. Future research is needed to explore evinacumab’s therapeutic targets beyond LDL-C to better modify risk factors for atherosclerosis, as well as CAV progression in heart transplant recipients. Presentation: Saturday, July 12, 2025