Gaetano De Ferrari, MD, is a professor and the Head of Cardiology at the University of Turin.

Gaetano De Ferrari, MD

A prespecified subanalysis of the VESALIUS-CV trial found evolocumab significantly reduced the risk of a first 

 across major subtypes in patients with atherosclerosis or high-risk diabetes but no prior MI or 

Gaetano De Ferrari, MD, of the University of Turin, presented the findings and discussed them with 

European Society of Cardiology (ESC) Congress 2026

VESALIUS-CV: Evolocumab Cuts First MI Risk 36%, With Gaetano De Ferrari, MD

VESALIUS-CV First MI Subanalysis Design and Results

The analysis characterized evolocumab's effect on first MI by type, ECG phenotype, and infarct size within the larger VESALIUS-CV trial, which previously showed evolocumab reduced the composite endpoint of coronary artery disease death, MI, and stroke.²

VESALIUS-CV randomly assigned 12,257 patients with qualifying atherosclerosis or high-risk diabetes, without prior MI or stroke and an LDL-C of at least 90 mg/dL, to evolocumab or placebo on background optimized lipid-lowering therapy. A blinded clinical events committee adjudicated and classified each MI according to the Universal Definition of Myocardial Infarction, ECG phenotype, and infarct size by peak troponin.¹

During a median follow-up of 4.6 years, 378 patients experienced an MI, and type 1 MI, now reclassified as primary MI under the newly released Fifth Universal Definition, accounted for 79% of events.¹

Evolocumab reduced the risk of any MI by 36% compared with placebo (5-year Kaplan-Meier estimate, 2.7% vs 4.1%; hazard ratio [HR], 0.64; 95% CI, 0.52-0.79; 

 <.0001), with cumulative incidence curves separating significantly by 6 months.¹ Risk reductions were consistent across MI type (type 1 HR, 0.61; type 2 HR, 0.70), ECG phenotype (NSTEMI HR, 0.63; STEMI HR, 0.64), infarct size, and key subgroups defined by LDL-C quartile, statin intensity, diabetes status, and presence of qualifying atherosclerosis.¹

Ferrari on Rethinking Primary and Secondary Prevention

Ferrari described the finding as a shift in how clinicians should think about lipid-lowering therapy timing.

"So far, PCSK9 [inhibitors] have been shown to be very effective in clear secondary prevention, that is treatment of patients that already had an event. This is the first and only study to assess the potential value of these agents and specifically evolocumab in patient[s] without an event... We should really prevent the first clinical manifestation before it occurs," Ferrari said.

Asked whether VESALIUS-CV challenges the traditional divide between primary and secondary prevention, Ferrari said the trial population sits in between the two categories. "We already know that patients with documented ASCVD are not really primary prevention because the plaque is already there. They're not traditionally secondary prevention, on the other hand, because they haven't had an event... I don't think it makes sense anymore to speak about primary prevention and secondary prevention. We should speak about risk, and once we define the risk, the higher the risk, the greater the benefit to start immediately with a very aggressive strategy," he said.

On the smaller, wider-confidence-interval benefit seen for type 2 MI, Ferrari offered a biological explanation rooted in plaque behavior. "My biological conclusion would be that among patients who did not have a myocardial infarction or an event previously, the biology of the plaque is influenced, and influenced even in a short term by evolocumab, therefore preventing the rupture of the plaque and the occurrence of spontaneous myocardial infarction. On the other hand, the type 2 or secondary myocardial infarction are mostly due to the slow build-up of plaques... It is reasonable to expect a greater efficacy on plaque composition and plaque rupture, as compared to percentage of stenosis and secondary myocardial infarctions," he said.

Ferrari also pointed to a residual treatment gap: patients who went on to have an MI were less likely to have been on a high-intensity lipid-lowering regimen at baseline, underscoring the continued importance of background statin and ezetimibe therapy alongside evolocumab. He closed with a reframing of how clinicians should view a patient's first cardiac event.

"The first myocardial infarction should not be considered the beginning of the treatment; it should be considered the failure of our prevention strategy," Ferrari said.

Editors’ note: De Ferrari reports relevant disclosures with Amgen and others.

De Ferrari GM, et al. VESALIUS-CV first MI: characterization of the effect of evolocumab on incidence of first myocardial infarction by type, ECG phenotype, and infarct size. Abstract #87346. Presented at: ESC Congress 2026; August 29, 2026; Munich, Germany.

Bohula EA, Marston NA, Bhatia AK, De Ferrari GM, et al; VESALIUS-CV Investigators. Evolocumab in patients without a previous myocardial infarction or stroke. N Engl J Med. 2026;394(2):117-127. doi:10.1056/NEJMoa2514428

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Gaetano De Ferrari, MD, breaks down VESALIUS-CV findings on evolocumab and first MI prevention across major infarct subtypes.

Gaetano De Ferrari, MD

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