Patients without AMI who take evolocumab have lower cholesterol levels

Reference

Giugliano RP, Pedersen TR, Park JG, et al, for the FOURIER Investigators. Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial. Lancet. 2017;390(10106):1962-1971.

Synopsis

This paper is a planned secondary analysis of an industry-sponsored randomized trial that tested a new kind of agent—a proprotein convertase subtilisin-kexin type 9 (PCSK9) monoclonal antibody called evolocumab (Repatha). The main trial enrolled more than 27,000 patients with stable cardiovascular disease and additional risk factors, and an LDL cholesterol level greater than 1.8 mmol/L (70 mg/dL) while taking optimal doses of a statin or ezetimibe (Zetia). The researchers randomized patients to receive evolocumab (140 mg subcutaneously every 2 weeks or 420 mg once a month according to patient preference) or matching placebo. They followed up for a median of 2 years, measuring a number of markers and assessing clinical outcomes. In the main report of the trial, patients using evolocumab had fewer nonfatal myocardial infarctions but had no benefit in cardiovascular or all-cause mortality. (See http://www.essentialevidenceplus.com/content/poem/190816.) In this secondary analysis (for which the funder collected and interpreted the data and helped edit the manuscript), the authors aimed to see how the LDL levels at 4 weeks correlated with outcomes and safety. They report data quite comparable with those from the original statin trials—patients who did not have cardiac events had lower average LDLs than those who had events. They also report no safety issues. According to GoodRx.com, evolocumab costs approximately $14,000 per year in the United States; it is about half that price in Canada and the United Kingdom. Let's be clear: This is **not** a trial in which patients are randomized to lipid targets. We have heard this story in the past. Randomized trials of statins were not conducted on the basis of achieving specific lipid targets. Extrapolations beyond the scope of the original research lead to guidelines with LDL targets that are easily measured but that can only be achieved through medication. Now that the statins are largely available as generic medications, the guidelines switched from lipid targets to "fire and forget."