The ODYSSEY Outcomes Trial in CVD

Deepak L. Bhatt, MD, MPH: The PCSK9 inhibitors really have terrific data at this point in time, with respect to effective LDL [low-density lipoprotein] reduction, safety, and now even clinical outcome reduction. The data from the FOURIER trial with evolocumab, for example, showed a significant reduction in important ischemic events in patients with stable atherosclerosis, whether that was coronary artery disease or cerebrovascular disease or peripheral artery disease. So people who are clinically stable, who are getting good therapy with statins and have LDLs that are reasonably well controlled, still benefited from the addition of evolocumab with no detectable downside in terms of some of the things that certain people and doctors were worried about—neurocognitive dysfunction, for example. There was no evidence of that in a carefully done substudy of FOURIER. Overall there is a really good risk profile, really good efficacy in important clinical events, and advance in terms of what we can do in patients with stable atherosclerosis beyond statin therapy.

The data for PCSK9 inhibition keeps growing. The data most recently, in terms of large outcome trials, came from the ODYSSEY Outcomes trial, which studied a PCSK9 inhibitor, alirocumab, and compared it with placebo in patients who were already receiving good background therapy, including statin therapy. In these patients who had a recent acute coronary syndrome—approximately 1 month to a year prior—there was a significant reduction in ischemic events. Additionally, at least in terms of nominal statistical significance, there was a lower rate of all-cause mortality as well. I think that really does advance the field in terms of a) validating the hypothesis that lower is better with respect to LDL cholesterol and b) that it can be done safely and effectively with PCSK9 inhibition.

Transcript edited for clarity.