How to Interpret Recent CV Outcome Trials and Future: PCSK9 Inhibitors

ABSTRACT

Based on evidence from numerous research studies, increased low-density lipoprotein cholesterol (LDL-C) is a clinically important factor for accelerated atherosclerosis and increased cardiovascular risk. The introduction of statin therapy has resulted in marked reductions in LDL-C and has proven to be clinically beneficial in cardiovascular events in patients with high cardiovascular risk. Nonetheless, many patients with elevated LDL-C do not achieve their LDL-C goals with current treatments. In addition, cardiovascular disease remains an important cause of mortality and morbidity worldwide. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors further reduce LDL-C, and potentially reducing cardiovascular events. Several PCSK9 inhibitors are currently under clinical development and some of them have been studied in completed cardiovascular outcome trials, including evolocumab, alirocumab, and bococizumab. The results of the FOURIER trial, which was the first cardiovascular outcome trial to examine the impact of PCSK9 inhibition with evolocumab therapy on cardiovascular events, were reported in March of 2017. The results of the ODYSSEY Outcomes trial with alirocumab therapy were released in March of 2018 at the American College of Cardiology Annual Scientific Session. The SPIRE-1 and -2 trials which examined a PCSK9 inhibitor, bococizumab, were prematurely terminated because of discontinued development of bococizumab in November 2016. This review will discuss 3 recent cardiovascular outcome trials with PCSK9 inhibitors, with an emphasis on clinical implications and future therapeutic perspectives.