‘Highest risk–highest benefit’ strategy: a pragmatic, cost-effective approach to targeting use of PCSK9 inhibitor therapies

Abstract

Cholesterol carried in low-density lipoprotein cholesterol (LDL-C) and other apolipoprotein B-containing lipoproteins plays a causal role in atherogenesis,^1–3 and, accordingly, is a key target in the prevention of atherosclerotic cardiovascular disease (ASCVD).^2,3 Clinical trial evidence indicates that the magnitude of the benefit from LDL-C lowering is independent of the means by which it is achieved and is proportionate to the absolute decrease in lipoprotein level.^1–4 Further, the relative risk reduction (RRR) appears the same, regardless of patient demographics and background medical history.^1–4 Most guidelines (e.g. Piepoli et al 2016)² recommend goals for LDL-C lowering that, while somewhat artificial and idealized constructs because the association between LDL-C and risk is continuous,¹ have been useful clinically as a metric of therapeutic success. In clinical practice, however, not all patients achieve their LDL-C goal with statins alone, and increasing recognition of this treatment gap has led to the need to consider the routine use of combination lipid-lowering therapies.