What Lessons Have We Learned and What Remains to be Clarified for PCSK9 Inhibitors? A Review of FOURIER and ODYSSEY Outcomes Trials

AbstractFor more than half a century, low-density  lipoprotein cholesterol (LDL-C) has been recognized as a major risk factor for incident atherosclerotic cardiovascular disease. The discovery of proprotein convertase subtilisin-kexin type 9 (PCSK9) in 2003, which prevents LDL-C receptor recycling, identified a new target for drug intervention. Re cently, two large-scale randomized clinical outcomes trials involving fully human anti-PCSK9 monoclonal antibodies tested the hypothesis that targeting this pathway would reduce cardiovascular events. Both the FOURIER (Further cardiovascular OUtcomes Research with PCSK9 Inhibition in subjects with E levated Risk) and ODYSSEY OUTCOMES trials met their primary efficacy endpoints, confirming findings reported earlier that major adverse cardiovascular events can be reduced by a further lowering of LDL-C beyond that achieved with statin therapy. In both trials, there were incremental reductions in L DL-C of> 50% from baseline, with no major safety concerns, over the trials ’ median follow-up time (2.2 and 2.8 years, respectively). While there were differences in design, lipid management and overall results, key messages from both studies were similar. However, post-publication, additional questions have arisen, especially regarding drug effects over the long-term, including a potential mortality benefit.

Source: Cardiology and Therapy - February 4, 2020 Category: Cardiology Source Type: research