Clinical Question

In patients at high risk of cardiovascular death, does the addition of evolocumab (Repatha) to statin therapy decrease cardiovascular-related mortality?

Bottom Line

Published data on the effectiveness of evolocumab in preventing cardiovascular-related mortality may not have represented the actual data in the clinical study report. When causes of death were readjudicated by a masked panel, cardiovascular deaths were numerically higher in the evolocumab group, although not to a level that reached statistical significance. (Level of Evidence = 1b−)

Synopsis

The FOURIER trial, a randomized controlled trial, originally reported a small benefit of evolocumab to reduce cardiovascular events when added to statin treatment in patients at high risk of death due to cardiovascular disease. There was no effect of treatment on cardiovascular or all-cause mortality. The report is a reanalysis of the study. Investigators were able to obtain the Clinical Study Report—the full technical description of the study used to support the approval of a medication— from Health Canada. They discovered that cause of death was determined by the local researcher, presumably not masked to treatment. However, the authors of the reanalysis developed a committee to read the case records of the 870 deaths that occurred in study participants to confirm or refute the stated cause of death. This masked analysis changed the cause of death in almost one-half (41.4%) of 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 = 1.28; 95% CI, 0.97 to 1.69; P = .078).