In patients at high risk of cardiovascular death, does the addition of evolocumab to statin therapy decrease cardiovascular-related mortality?
A little sleight of hand here, perhaps unintended (perhaps not): Published data on the effectiveness of evolocumab to prevent mortality may not have represented the actual data in the clinical study report. When causes of death were re-adjudicated by a masked panel, cardiovascular deaths were numerically higher in the evolocumab group, though not to a level that reached statistical significance.
Plan de l'etude:
Meta-analysis (randomized controlled trials)
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).
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine