Treatment of severe hypertriglyceridaemia

Abstract

We welcome the Review by Robert Hegele and colleagues about the defi nition, diagnosis, and management of hypertriglyceridaemia. In particular, we note that the simplification of hypertriglyceridaemia into two easily identifiable groups (individuals with mild-to-moderate hypertriglyceridaemia [2–10 mmol/L] and those with severe hypertriglyceridaemia [>10 mmol/L]) is a logical step that allows clinicians to focus on the clinical priority in each group—ie, prevention of cardiovascular disease in patients with mild-to-moderate hypertriglyceridaemia and acute pancreatitis in those with severe hypertriglyceridaemia. However, we disagree with the authors’ recommendation that fibrate therapy in particular, along with nicotinic acid and omega-3 fatty acids, and not statins, should be used as the optimum drug option in severe hypertriglyceridaemia to prevent pancreatitis. Treatment with highdose statins can lower triglycerides to a similar extent as noted with nicotinic acid and omega-3 fatty acids and, as Hegele and colleagues highlight, statins are only moderately weaker than are fi brates in this regard. Moreover, pooled data from major placebo-controlled and standard carecontrolled randomised trials for statins (16 trials, 113 800 participants) and fi brates (7 trials, 40 162 participants), suggest that medium-term treatment (2–7 years) with a statin reduces the risk of pancreatitis by more than 20%, whereas fi brates might actually increase risk of pancreatitis, possibly because of contrasting eff ects on the development of gallstones. These meta-analyses had design weaknesses: the trials were not done in people with severe hypertriglyceridaemia, identifi cation of pancreatitis was not recorded in a standardised way, and no pancreatitis analyses were prespecifi ed. Nonetheless, these results provide the only source of unbiased, large-scale, randomised trial data on whether lipidmodifying drugs aff ect pancreatitis risk in any population. Data from a drug application document submitted to the US Food and Drug Administration in 2011 about the SHARP trial also suggested that the risk of development of pancreatitis in patients given combination treatment of simvastatin and ezetimibe was reduced by 40% compared with placebo. Our view is that—along with attention to lifestyle and secondary factors, as Hegele and colleagues discussed—clinicians should treat s e v e r e h y p e r t r i g l y c e r i d a e m i a m a i n l y w i t h s t a t i n s . F o r individuals with particularly severe hypertriglyceridaemia at diagnosis, plus patients whose triglyceride concentrations do not respond adequately to statin monotherapy (ie, triglycerides remain >10mmol/L), clinicians should add a fibrate or omega-3 fatty acid to this regimen. For most people with triglyceride concentrations less than 20 mmol/L at diagnosis, statin monotherapy will be adequate and it seems to be the option best supported by evidence for both cardiovascular risk and pancreatitis risk reduction.