New therapeutic approaches for the treatment of hypertriglyceridemia.

ABSTRACT

Patients with hypertriglyceridemia (> 150 mg/dl) have an increased risk for atherosclerotic cardiovascular disease, and those with severe hypertriglyceridemia (> 880 mg/dl) also for pancreatitis. The currently available medications to decrease triglyceride levels, such as fibrates, statins, and omega­3 fatty acids, are in many cases not able to achieve normal triglyceride levels. Therefore, new drugs are in development to address this unmet need. Recently, icosapent ethyl, a purified formulation of the omega-3-fatty acid eicosapentaenoic acid, was approved in Germany for the reduction of cardiovascular events in patients with hypertriglyceridemia and established cardiovascular disease or with diabetes and other risk factors on top of statins. Other new drugs in development are the more selective peroxisome proliferator-activated receptor α (PPARα) modulator, pemafibrate, already approved for the treatment of hypertriglyceridemia in Japan, and inhibitors of ApoC-III and angiopoietin-like 3 (ANGPTL3) in the form of antisense oligonucleotides or siRNAs or fully human monoclonal binding antibodies. Apolipoprotein C-III and ANGPTL3 protein seem to be quite promising targets based on solid genetic data. Larger studies of long duration, many of them currently ongoing, are needed to establish the role these medications will play in the treatment of hypertriglyceridemia in clinical practice.