Evolocumab in Patients at High Cardiovascular Risk Without Prior MI or Stroke: Primary Results of the VESALIUS-CV Trial 

Dr. Leiter:
Hello from AHA 2025 here in New Orleans. I'm Dr. Lawrence Leiter, and I'm very pleased to share with you key findings from the VESALIUS-CV trial, which were just presented and published simultaneously in TheNew England Journal of Medicine.

VESALIUS-CV is the first large-scale study evaluating a PCSK9 inhibitor, evolocumab, for cardiovascular risk reductions in patients at high CV risk but without prior MI or stroke. The study enrolled over 12,000 patients at high CV risk. To get into the study, patients had to have either coronary disease without prior MI, cerebrovascular disease without prior stroke, peripheral arterial disease, or high-risk diabetes. Patients had to have an elevated LDL above 90 or non-HDL above 120, or ApoB greater than 80 despite statin therapy.

The results were very exciting. There were 2 primary endpoints: 3-point MACE—so CHD mortality, MI, or stroke—reduced by a significant 25%; a 4-point MACE, which also included urgent need for revascularization, reduced significantly by 19%. Perhaps even more impressively, CV mortality reduced by 21%. Total mortality—the ultimate endpoint—reduced by significant 20%.

And importantly, there was no heterogeneity observed. Similar benefit was observed in all of the patient groups, including the so-called primary prevention cohort of high-risk diabetes.

So I think these results are practice-changing in a number of ways. Firstly, the study greatly expands the populations for which we now have definitive evidence that intensive LDL lowering with evolocumab significantly reduces cardiovascular events.

But I think perhaps most importantly, in terms of a final take-home message, we’ve been saying for years now that when it comes to LDL reduction, lower is better. I think the major practice-changing element of VESALIUS-CV is also going to emphasize the fact that earlier is better. We shouldn't wait until a patient has a clinical event and only then reduce their LDL intensively; we need to find our high-risk patients and lower their LDL intensively prior to having a first event.

From AHA 2025, I'm Dr. Lawrence Leiter, and thank you for watching.