Triglyceride-lowering trials.

PURPOSE OF REVIEW: We provide an overview of current evidence about the independent role of high triglyceride levels for cardiovascular risk and for acute pancreatitis.

RECENT FINDINGS: Natural experiments of Mendelian randomization have given us a deeper understanding about the molecular pathways involved in triglyceride metabolism. Individuals with low-triglyceride levels generally have lower rates of cardiovascular disease (CVD). There has been a significant growth in the development of new agents that modulate enzymes involved in a variety of aspects of triglyceride packaging into VLDL or chylomicron particles, and triglyceride catabolism. Antisense inhibitors of apolipoprotein CIII are being tested, as are a variety of agents designed to increase lipoprotein lipase activity. Large-scale trials are underway with purified fatty acid (FA) formulations in over 20 000 individuals in aggregate. A large study of a new fibrate is underway.

SUMMARY: A focus on patients with elevated triglyceride levels is a new paradigm not previously the focus of large trials. Clinical outcome data on cardiovascular risk reductions remains sparse. Some drugs are already approved for use in rare inherited disorders predisposing to severe hypertriglyceridaemia and acute pancreatitis. Safety and costs issues are critical.