Unmet Need for Adjunctive Dyslipidemia Therapy in Hypertriglyceridemia Management

Abstract

Despite the important role of high-intensity statins in reducing atherosclerotic cardiovascular disease events in secondary and primary prevention, substantial residual risk persists, particularly among high-risk patients with type 2 diabetes mellitus, metabolic syndrome, and obesity. Considerable attention is currently directed to the role that elevated triglycerides (TGs) and non-high-density lipoprotein cholesterol levels play as important mediators of residual atherosclerotic cardiovascular disease risk, which is further strongly supported by genetic linkage studies. Previous trials with fibrates, niacin, and most cholesterol ester transfer protein inhibitors that targeted high-density lipoprotein cholesterol raising, and/or TG lowering, have failed to show conclusive evidence of incremental event reduction after low-density lipoprotein cholesterol levels were "optimally controlled" with statins. Although omega-3 fatty acids are efficacious in lowering TG levels and may have pleiotropic effects such as reducing plaque instability and proinflammatory mediators of atherogenesis, clinical outcomes data are currently lacking. Several ongoing randomized controlled trials of TG-lowering strategies with an optimal dosage of omega-3 fatty acids are nearing completion.

Rounding the corner on residual risk: Implications of REDUCE‐IT for omega‐3 polyunsaturated fatty acids treatment in secondary prevention of atherosclerotic cardiovascular disease

“…In recent decades, statins have become the mainstay of lipid‐lowering therapy to reduce risk of CV events in patients with atherosclerotic cardiovascular disease (ASCVD) . Statin therapy, which primarily targets low‐density lipoprotein cholesterol (LDL‐C), has a firmly established role in reducing the risk of CV events by 25% to 35% in such patients . The reduction in risk is related to the absolute reduction in LDL‐C levels .…”

“…Large‐scale, randomized trials have examined three classes of treatments targeting TG levels: fibrates, niacin, and omega‐3 PUFAs. These trials have been thoroughly discussed by other recent reviews, so we will briefly summarize the state of the field up to 2018. Then we will discuss very recent studies, including three trials of omega‐3 PUFAs that were published in 2018.…”

“…As noted by prior reviews, trials of fibrates or niacin added to statin therapy have failed to show a benefit of the added treatment in terms of CV event rates . The ongoing PROMINENT trial, involving the novel fibrate pemafibrate, may provide insight into this question (NCT03071692).…”

“…The trial demonstrated that treatment with a high dose (4 g per day) of the omega‐3 polyunsaturated fatty acid (PUFA) icosapent ethyl significantly reduced the risk of ischemic cardiovascular (CV) events and CV death in patients who (a) were on a stable dose of statin, (b) had established CV disease or type 2 diabetes mellitus and at least one additional CV risk factor, and (c) had elevated triglyceride (TG) levels at baseline (>135 or 150 mg/dL). These results were remarkable because they followed a series of major TG‐lowering trials that had failed to achieve reductions in CV outcomes in similar groups of patients . Why was REDUCE‐IT different?…”

Icosapent ethyl for dyslipidaemia in patients with diabetes and coronary artery disease: Act now to reduce it

“…However, existing clinical guidelines generally do not recommend the use of triglyceride‐reducing or HDL‐C‐raising medications in combination with statin therapy for reduction of ASCVD risk because of the absence of robust evidence demonstrating efficacy with adjunctive medications such as fibrates and niacin . Interest in the effects of oral supplementation with high‐dose omega‐3 fatty acids on reducing triglycerides and ASCVD risk has been rekindled recently …”