Pharmacologic approaches for the management of patients with moderately elevated triglycerides (150–499 mg/dL)

Evolving Role of Non‐Statin Therapy for the Management of Dyslipidemia and Cardiovascular Risk Reduction: Past, Present, and Future

“…The fibrates, gemfibrozil and fenofibrate derivatives, are primarily considered TG‐lowering therapies but are also effective at reducing non–HDL‐C. Although fibrates have been shown to reduce ASCVD risk when used as monotherapy in placebo‐controlled trials, only the Action to Control Cardiovascular Risk in Diabetes (ACCORD)‐Lipid trial prospectively evaluated the utility of adding a fibrate to statin therapy in patients with diabetes . Surprisingly, the combination of fenofibrate and simvastatin did not reduce ASCVD risk when compared to simvastatin monotherapy; however, the subgroup of patients with TG levels ≥204 mg/dl and HDL‐C levels ≤34 mg/dl had lower cardiovascular event rates with combination therapy compared to statin monotherapy .…”

“…Omega‐3 fatty acids (O3FA) are primarily TG‐lowering therapies containing a combination of the long‐chain fatty acids, docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA). Of the FDA‐approved products, omega‐3 ethyl esters and omega‐3 carboxylic acids contain both DHA and EPA, whereas icosapent ethyl contains only EPA . Although low‐dose O3FA appears to modestly reduce ASCVD risk and mortality in patients with heart failure, there is little evidence to support adding O3FA to statin therapy to reduce ASCVD risk .…”

“…Of the FDA‐approved products, omega‐3 ethyl esters and omega‐3 carboxylic acids contain both DHA and EPA, whereas icosapent ethyl contains only EPA . Although low‐dose O3FA appears to modestly reduce ASCVD risk and mortality in patients with heart failure, there is little evidence to support adding O3FA to statin therapy to reduce ASCVD risk . The only available data are from the Japan EPA Lipid Intervention Study (JELIS) trial, which found a reduction in cardiovascular events with EPA 1.8 g/day on top of background statin therapy, compared to statin therapy alone .…”

“…Elevated TG levels have consistently been associated with increased ASCVD risk, yet the role of TG as an independent risk factor remains controversial . As such, there are ongoing clinical trials to evaluate the potential of TG‐lowering therapies to reduce residual risk, as well as several novel therapies currently in development.…”

“…As such, there are ongoing clinical trials to evaluate the potential of TG‐lowering therapies to reduce residual risk, as well as several novel therapies currently in development. Both the Reduction of Cardiovascular Events with EPA–Intervention Trial (REDUCE‐IT) and Outcomes Study to Assess Statin Residual Risk Reduction with Epanova in High CV Risk Patients with Hypertriglyceridemia (STRENGTH) trials are randomized clinical outcome trials evaluating O3FA prescription products, icosapent ethyl and omega‐3 carboxylic acids, in patients at high ASCVD risk with moderately elevated levels of TG receiving background statin therapy . Novel therapies include an antisense oligonucleotide (volanesorsen) and angiopoietin‐like protein (ANGTL) 3 inhibitor (evinacumab), which are both currently in phase III and II clinical trials, respectively.…”