A prespecified secondary analysis of the VESALIUS-CV trial found that evolocumab (Repatha; Amgen), a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, was associated with a 20% relative reduction in all-cause mortality among high-risk patients with qualifying atherosclerosis or diabetes who had not experienced a prior myocardial infarction (MI) or stroke.
The findings provide evidence of a mortality benefit with evolocumab in a high-risk population without a history of MI or stroke.
The analysis also adds to evidence supporting intensive low-density lipoprotein cholesterol (LDL-C) lowering earlier in the course of cardiovascular disease.
“For people at high risk of a heart attack or stroke, lowering LDL-C or ‘bad’ cholesterol with Repatha may do more than help prevent these events; it may also reduce the risk of dying from heart disease and its serious consequences,” said Jay Bradner, MS, executive vice president, Research and Development, Artificial Intelligence and Data at Amgen, in a statement.
VESALIUS-CV was a double-blind, placebo-controlled trial that randomized 12,257 patients (median age, 66 years; 43% women) with qualifying atherosclerosis or high-risk diabetes, no previous MI or stroke, and an LDL-C level of at least 90 mg/dL—or comparable non–high-density lipoprotein cholesterol or apolipoprotein B thresholds—to receive evolocumab 140 mg subcutaneously every 2 weeks or placebo.
Over a median follow-up of 4.6 years, 973 patients (7.9%) died: 36% from cardiovascular causes, 51% from noncardiovascular causes, and 13% from undetermined causes.
All-cause mortality occurred in 434 patients in the evolocumab group vs 539 patients in the placebo group, corresponding to 5-year Kaplan-Meier rates of 7.9% and 9.7%, respectively.
The reduction was also observed for cardiovascular mortality.
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Mortality from noncardiovascular causes was numerically lower with evolocumab.
The mortality benefit emerged gradually, with a landmark analysis finding no difference between treatment groups during the first 1.5 years, followed by a 27% relative reduction in mortality after 1.5 years.
Among cause-specific cardiovascular deaths, evolocumab showed directionally favorable effects for acute MI, stroke, and heart failure, but not sudden cardiac death.
A multistate model examined whether nonfatal cardiovascular events occurring after randomization were associated with subsequent mortality.
Patients who experienced a postrandomization MI, ischemic stroke, or ischemia-driven revascularization had substantially higher subsequent mortality risk.
The model estimated that approximately 78% of the treatment effect on noncardiovascular mortality could be statistically attributed to preventing these antecedent nonfatal cardiovascular events.
This finding suggests that preventing a first cardiovascular event may have downstream effects on survival.
They have resources available for clinicians to learn more about the management of cardiovascular disease.
