
Ischaemic heart disease remains the main cause of death worldwide. 1 Within its multifactorial aetiology low-density lipoprotein (LDL) and other apolipoprotein (apo) B-containing lipoproteins play a central, causal role, promoting the development of the underlying process of atherosclerosis. The use of statins and other drugs—ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, bempedoic acid—to lower LDL is a central strategy in the prevention of atherosclerotic cardiovascular disease (ASCVD) in both primary and secondary settings. 2 However, in many individuals, a substantial ASCVD risk remains after LDL-cholesterol (LDL-C) goal achievement, and elevated plasma triglyceride (TG) is recognised as an important component of this residual risk. 3 Plasma TG, or more specifically TG-rich lipoproteins (TRL), is therefore an additional target for lipid-lowering therapy. Outcome studies of TG lowering using classical drugs such as fibrates and high-dose niacin when added to statins failed to demonstrate further ASCVD risk reduction, although retrospective analyses suggest that subgroups characterised by high TG and low high-density lipoprotein (HDL) may have positive results. 4–7 An alternative approach, treatment with high-dose eicosapentaenoic acid (EPA), has been shown to reduce cardiovascular risk in patients with (and without) hypertriglyceridaemia who are on statins. 8–10
This review explores the concepts behind, and practical implementation of, an evidence-based therapeutic strategy that tailors further intervention according to the plasma lipid profile in patients on standard statin therapy who are often undertreated. 11
Genetic analyses provide robust evidence that elevated TG is a causal risk factor for ASCVD 12 13 and underpin the finding from epidemiological studies that raised TG levels are positively and linearly related to cardiovascular risk (figure 1A). 14 15 The importance of these observations is that they reveal an often unaddressed major risk factor that is of particular relevance in people with obesity or type 2 diabetes in whom TG levels are frequently elevated. 16 Further, outcome trials have shown that elevated TG levels (again especially in type 2 diabetics) are associated with high residual cardiovascular risk in statin-treated patients with established cardiovascular disease, even if they have well-controlled LDL-C. 17–19.