Patients with prior percutaneous coronary intervention (PCI) but no history of myocardial infarction (MI) or stroke experienced significant reductions in major adverse cardiovascular events (MACE) with evolocumab therapy in a new analysis presented at EuroPCR 2026 (19–22 May, Paris, France).
The findings, drawn from a subgroup analysis of the VESALIUS-CV trial were presented by Brian Bergmark (Brigham and Women’s Hospital, Boston, USA) and concurrently published in Circulation. Results from the study suggest that intensive low-density lipoprotein (LDL) cholesterol lowering with a PCSK9 inhibitor may benefit a patient population that is currently classified as “high risk”, but not necessarily “very high risk”, stated Bergmark, under contemporary lipid management guidelines.
Bergmark reported outcomes in 3,627 patients with a history of prior PCI enrolled in the VESALIUS-CV study. Participants had established atherosclerotic cardiovascular disease (ASCVD), but no prior MI or stroke, and were receiving optimised lipid-lowering therapy with or without ezetimibe. Patients were randomised to receive evolocumab 140mg every two weeks or matching placebo.
Dual primary endpoints included a three-point MACE composite of coronary heart disease death, MI, or ischaemic stroke, and a four-point MACE endpoint that included ischaemia-driven coronary revascularisation.
The median patient age was 66 years, with 43% of participants presenting with diabetes. Most patients were receiving statin therapy (89%), including 71% on high-intensity statins, while one quarter were prescribed ezetimibe. Median LDL cholesterol at baseline was 3mmol/L, and the median time since most recent PCI was four years.
According to Bergmark, patients with prior PCI represented a “particularly high-risk” cohort. In the placebo arm, these patients experienced a 43% higher risk of the three-point MACE endpoint and a 66% higher risk of the four-point MACE endpoint compared with patients without prior PCI. Rates of MI, including both non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI), as well as ischaemia-driven revascularisation were also significantly higher.
Treatment with evolocumab reduced LDL cholesterol by 61% at 48 weeks, achieving levels of approximately 1mmol/L throughout the study period. This translated into a 30% relative risk reduction in the three-point MACE endpoint compared with placebo (7.0% vs. 9.5%), alongside an 18% reduction in the four-point MACE endpoint (17.9% vs. 21.7%), Bergmark described to the EuroPCR audience.
“The benefit of evolocumab was consistent regardless of baseline LDL cholesterol and as such, the large differences in LDL cholesterol levels achieved with evolocumab in VESALIUS-CV likely reflect the potential benefit in clinical practice,” Bergmark stated.
Importantly, MI rates were reduced by 50% with evolocumab (3.0% vs. 6.1%), with statistically significant differences emerging “as early as six months” after randomisation, the speaker highlighted. Both STEMI and NSTEMI rates were lower in the evolocumab arm, with relative reductions of 60% and 45%, respectively.
During discussion, the findings prompted debate regarding how these data should influence current lipid-lowering strategies in post-PCI patients without prior MI.
To this, Bergmark commented that: “Of course, the notion exists that people should be fully optimised on statin therapy, and ezetimibe should be added in practice, but that rarely occurs. Only 50% of people in the USA have their LDL level checked within six months of a PCI for stable coronary disease, much less with medication optimisation.
“I think this population reflects what’s happening in the real world. These are experienced trial sites who consider their patients to be as optimised as possible on those medications,” the speaker continued.
Panellist Roxana Mehran (Icahn School of Medicine at Mount Sinai, New York, USA) described the MI reduction of 50% as “unheard of” in a large contemporary trial population, noting that the findings must reinforce that PCI patients are at “very high risk” for residual events.
Continuing, Mehran said: “I think this is important and it behoves us that, as great as our interventions and our tools are, they are not going to be great in avoiding and averting events in non-target lesions or anywhere else. So, to make our interventions durable, we have to pair it with prevention.”
Concluding the presentation, Bergmark stated that, in light of the current findings, when “clearly high-risk” patients are identified, “and I believe these patients should be identified as such,” he added, “aggressive” treatment should be sought.
Following his presentation, Bergmark elaborated on how he sees evolocumab fitting into real-world lipid-lowering pathways alongside statins and ezetimibe. He told Cardiovascular News that there is a “longstanding tension between what people wish happened and what actually happens in the world”.
“In an idealised mindset, you would like to know the benefit of this drug in patients who are on every lipid-lowering drug, who are no longer smoking, control their diabetes perfectly and run a marathon every day. But those people don’t exist,” he said. Rather, these are patients who are considered by an experienced team to be on an optimised regimen, stated Bergmark.
Commenting on the dramatic reduction in MI in their analysis and what drove this benefit in prior PCI patients, Bergmark said that “from a purist perspective”, this cannot be spoken to.
“Mechanistically, what accounts for the effect can’t be discerned beyond the LDL-lowering. But it does speak to the fact that these patients were particularly at risk for coronary events,” he continued. “There are patients who for other reasons might have been more at risk for diffuse atherosclerotic events throughout the body—these are patients really with high coronary risk—and [evolocumab] seems to have a really powerful effect on that biology.”
