The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The secondary endpoint was also a composite — cardiovascular death, myocardial infarction, or stroke.2
Greater than 80% of the patients enrolled had a prior myocardial infarction, and there were no significant differences between the placebo and evolocumab groups for the demographic characteristics reported. Further, 69% of the patients enrolled were already on high-intensity statin therapy and another 30% were on moderate-intensity statin therapy.
There was clearly a significant drop in the mean LDL from 92 mg/dL at baseline to 30 mg/dL in the evolocumab group. The authors also report significant decreases in both the primary and secondary composite endpoints from 11.3% and 7.4% in the placebo groups to 9.8% and 5.9% in the evolocumab groups respectively.2
While the absolute risk reduction for the composite endpoints was not reported, it was calculated to be 1.5% based on the results that were reported. As with many similar studies, this small decrease in risk is magnified by the authors when they report only the relative risk reductions, which range from 15% to 20%, depending on the composite endpoint evaluated. When the outcomes of the composite endpoints were evaluated independently, there were no significant differences in cardiovascular death between the placebo and the evolocumab groups.
Likewise, death from any cause, hospitalizations for unstable angina, or the composite of death or hospitalizations for worsening heart failure were not significantly different between groups.
While cardiovascular mortality was not a primary endpoint evaluated, surely, we’ll be hearing pharmaceutical reps cite the relative risk reductions ad nauseam. So it is important to consider that while there were significant reductions in the primary and secondary composite endpoints, this trial did not show an improvement in cardiovascular mortality when it was evaluated independent from the composite endpoints.
While it is important to note that the trial was not designed to evaluate cardiovascular mortality, when considering this expensive drug for our patients we should keep in mind that its effect on mortality remains unknown. Despite its fantastic efficacy at reducing LDL, non-fatal MI, or stroke these reduction did not translate into a mortality benefit during the study period.
The authors explained that the data suggest that clinically significant reductions in LDL levels require time to translate into clinical benefit, because the greatest differences between the groups were found in the second year of follow-up. The implication is obviously that we should treat patients for longer periods of time. Unfortunately, we need a longer study in order to support that claim with sufficient evidence.