Cholesterol-reducer evolocumab associated with a nonsignificant increase in cardiovascular mortality (FOURIER)

Reference

Erviti J, Wright J, Bassett K, et al. Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: a reanalysis based on regulatory data. BMJ Open 2022;12(12):e060172.

Synopsis

The FOURIER trial, a randomized controlled trial, originally reported a small benefit of evolocumab (Repatha) to reduce cardiovascular events when added to statin treatment in patients at high risk of death due to cardiovascular disease. As we pointed out, there was no effect of treatment on cardiovascular or all-cause mortality. This report is a reanalysis of the study. After getting stonewalled by the U.S. Food and Drug Administration, the investigators were able to obtain the Clinical Study Report — the full technical description of the study used to support approval of a medicine — from Health Canada. They discovered that cause of death was determined by the local researcher, presumably not masked to treatment. However, the authors of this reanalysis developed a committee to read the case records of the 870 deaths occurring in study participants (939 pages of narrative!) to confirm or refute the stated cause of death. This masked analysis changed the cause of death in almost half (41.4%) the data; when these results were reanalyzed, cardiac deaths were numerically but nonsignificantly higher in the evolocumab group (n= 113) than in the placebo group (n= 88; relative risk [RR] 1.28; 95% CI 0.97 - 1.69; P = .078).