The emerging role of proprotein convertase subtilisin/kexin type-9 inhibition in secondary prevention

PURPOSE OF REVIEW: The recent advent of a highly efficacious class of low-density lipoprotein cholesterol (LDL-C) lowering agents, the proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors, has transformed dyslipidaemia management in patients with cardiovascular disease as well as those with familial hypercholesterolemia. RECENT FINDINGS: Recent positive results of the landmark Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk cardiovascular outcome trial with evolocumab as an add-on to statin therapy demonstrate further reduction of cardiovascular events. Additional safety outcomes from this large randomized trial, as well as the EBBINGHAUS substudy, allay fears of neurocognitive disorder as an adverse effect of achieving very low LDL-C levels with these agents. SUMMARY AND IMPLICATIONS: Widespread clinical adoption of PCSK9 inhibitors will depend on the results from ongoing and planned cardiovascular efficacy and safety trials with PCSK9 inhibitors. In addition, understanding the practical challenges and barriers to usage of these injectable agents by high cardiovascular risk patients will also affect clinical adoption of this class of agents. Analysis of cost-benefit models, along with anticipated updates to practice guidelines for dyslipidaemia management are likely to strengthen the clinical utility of PCSK9 inhibitors. Importantly, the potency of this new class of agents provides a huge opportunity to extend further the 'lower LDL-C is better' hypothesis in an effort to reduce rates of cardiovascular morbidity and mortality on a population level.