Key result
Evolocumab cuts total 3-point MACE by ~27% compared with placebo.
Why the study?
While PCSK9 inhibition with evolocumab is known to reduce first major cardiovascular events in high-risk patients without prior MI or stroke, its effect on recurrent and total cardiovascular events—which reflect overall health status and healthcare costs—remained to be evaluated.
Does evolocumab added to optimized lipid-lowering therapy reduce first, recurrent, and total major cardiovascular events in patients with atherosclerosis or high-risk diabetes and no prior MI or stroke?
RCT (n=12,257)
Placebo-controlled
Randomized
Does evolocumab added to optimized lipid-lowering therapy reduce first, recurrent, and total major cardiovascular events in patients with atherosclerosis or high-risk diabetes and no prior MI or stroke?
Adding evolocumab to statin therapy significantly reduces both first and subsequent major adverse cardiovascular events in high-risk patients without a prior MI or stroke, preventing nearly double the number of 4-P MACE events when accounting for total events rather than first events alone.
Background PCSK9 inhibition with evolocumab reduced the risk of a first major cardiovascular event in high-risk patients with no prior MI or stroke in the VESALIUS-CV trial. Recurrent major cardiovascular events are common and important to patients, clinicians, and healthcare systems as they provide additional information regarding overall health status and total costs. Purpose To evaluate the effect of evolocumab on not only first, but also recurrent and total cardiovascular events. Methods The VESALIUS-CV trial randomized patients with qualifying atherosclerosis or high-risk diabetes, no prior MI or stroke, and an LDL-C ≥ 90mg/dL on optimized lipid-lowering therapy to evolocumab or placebo. The dual primary endpoints (PEP) were a composite of coronary heart disease death (CHD death), MI or ischemic stroke (3-P MACE) and 3-P MACE with the addition of ischemia-driven arterial revascularization (IDR)(4-P MACE).In this prespecified analysis, total dual PEP events (ie, first and subsequent) were analyzed using a negative binomial regression model. Results Among 12,257 patients followed for a median of 4.6 years, there were 779 first 3-P MACE and 146 subsequent events (19% more) for 925 total events. For 4-P MACE, there were 1654 first events and 1107 subsequent events (67% more) for 2,761 total events.Evolocumab reduced the risk of first 3-P MACE by 25% (HR 0.75, 95% CI 0.65-0.86), recurrent events by 37% (incidence-rate ratio [IRR] 0.63, 95% CI 0.42-0.94) and total events by 27% (IRR 0.73, 95% CI 0.63-0.86; p<0.001)(Figure). Likewise for 4-P MACE, evolocumab reduced the risk of first events by 19% (HR 0.81, 95% CI 0.73-0.89), recurrent events by 25% (incidence-rate ratio [IRR] 0.75, 95% CI 0.61-0.91), and total events by 20% (IRR 0.80, 95% CI 0.71-0.90; p<0.001)(Figure). For every 1000 patients treated for 5 years, evolocumab prevented 20 first 3-P MACE events, 5 subsequent events and 25 total events. Similarly, for every 1000 patients treated for 5 years, evolocumab prevented 31 first 4-P MACE events, 24 subsequent events and 55 total events. Results were consistent across key subgroups, including by qualifying atherosclerosis and high-risk diabetes without atherosclerosis, age, sex, and statin intensity. Conclusions The addition of the PCSK9 inhibitor evolocumab to statin therapy significantly reduced the rate of total MACE. For 4-P MACE, close to double the number of events were prevented with evolocumab vs placebo as compared with the analysis of only first events. These data provide further support for the role of intensive LDL-C lowering to reduce the first and subsequent MACE in patients with atherosclerosis or high-risk diabetes and no prior MI or stroke.
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Jc et al. (2026) conducted an RCT in Qualifying atherosclerosis or high-risk diabetes with no prior myocardial infarction or stroke (n=12,257). Evolocumab vs. Placebo was evaluated on Total dual primary endpoints: 3-point MACE (coronary heart disease death, MI, or ischemic stroke) and 4-point MACE (3-P MACE plus ischemia-driven arterial revascularization) (IRR 0.73, 95% CI 0.63-0.86, p=<0.001). Evolocumab reduced total 3-P MACE events by 27% (IRR 0.73, 95% CI 0.63-0.86; p<0.001) and total 4-P MACE events by 20% (IRR 0.80, 95% CI 0.71-0.90; p<0.001) vs placebo.
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