Nicholas Marston, MD, MPH, is a cardiologist and an assistant professor of medicine at Brigham and Women's Hospital.

Nicholas Marston, MD, MPH

Evolocumab Reduces CV Risk in Non-Atherosclerotic Patients With Diabetes, With Nicholas Marston, MD, MPH

Evolocumab has the capacity to reduce the risk of first major cardiovascular event (MACE) in patients without known significant 

, according to a secondary analysis of the VESALIUS-CV trial.

American College of Cardiology (ACC) Scientific Sessions 2026

 in New Orleans, Louisiana, by Nicholas Marston, MD, MPH, a preventive cardiologist at Brigham and Women’s Hospital and an assistant professor of medicine at Harvard Medical School, these data highlight the oral PCSK9 inhibitor’s capacity for expanding treatment to patients without a history of major cardiovascular events. The analysis demonstrates the importance of targeting lower LDL-C goals across high-risk primary patients.

“We often think about diabetes as a CAD equivalent,” Marston told 

 in an exclusive interview. “But if you look at the guidelines, we aren’t as aggressive with treating LDL-C levels in patients with diabetes as we are in those who are secondary prevention with coronary disease, especially if they’ve had an event. I think these results demonstrate that we really should be treating them more similarly, at least in terms of their LDL-C goals.”

VESALIUS-CV was a randomized, double-blind, placebo-controlled trial of evolocumab, involving 12,257 patients with qualifying atherosclerosis or high-risk diabetes. The latter was defined as ≥10 years’ duration, daily insulin use, or microvascular disease. Eligible patients also had to present with no prior myocardial infarction or stroke, an LDL-C level ≥90 mg/dL, a non-HDL-C level ≥120 mg/dL, and an apolipoprotein-B (apoB) level ≥80 mg/dL.

In the present analysis, Marston and colleagues examined outcomes in patients without known significant atherosclerosis, which was defined as any arterial stenosis ≥50% or CAC ≥100. The study included dual primary endpoints – the first was a composite of coronary heart disease death, myocardial infarction, or ischemic stroke (3-P MACE), while the other was 3-P MACE plus ischemia-driven arterial revascularization (IDR) (4-P MACE). Secondary endpoints included the following composites:

Myocardial infarction, ischemic stroke, or IDR

Coronary heart disease death, myocardial infarction, or IDR

Cardiovascular death, myocardial infarction, or ischemic stroke

Coronary heart disease death or myocardial infarction

The sub-analysis cohort included a total of 3655 patients with a median age of 65 years, followed for a median of 4.8 years. Median body mass index was 31.4 (interquartile range [IQR], 28-35.6), most patients had hypertension, and all patients had diabetes. The median baseline LDL-C level was 132 mg/dL (IQR, 108-156).

Ultimately, a 3-P MACE occurred in 83 patients in the evolocumab group compared to 117 in placebo (HR, 0.69; 95% CI, 0.52-0.91; 

 = .009; between-group risk difference, 2.1%; 95% CI, 0.4-3.8%). A 4-P MACE occurred in 127 patients in the evolocumab group versus 178 in the placebo group (HR, 0.69; 95% CI, 0.55-0.86; 

 = .001; between-group risk difference, 2.9%; 95% CI, 0.9-4.9%). Evolocumab’s effect was also more apparent after the first year of treatment, with 41% (HR, 0.59; 95% CI, 0.43-0.81) and 39% (HR, 0.61; 95% CI, 0.48-0.79) reductions in the risk of 3- and 4-P MACE afterwards, respectively.

“Because this patient population was high-risk primary prevention with diabetes, we do have to keep that caveat in terms of generalizability; however, I think we can certainly say that these data support intensifying treatment and LDL-C goals in those patients,” Marston said. “Really, what we should be doing is treating these high-risk diabetes patients to the kind of targets that we reserve for secondary prevention.”

Editors’ Note: Marston reports disclosures with Ionis, Lilly, Arrowhead, Janssen, Amgen, New Amsterdam, and others.

Marston N, Bohula E, Bhatia A, et al. Evolocumab Reduces Risk of First Major Cardiovascular Events by 31% in Patients Without Significant Atherosclerosis: Results from VESALIUS-CV. Abstract presented at the American College of Cardiology Scientific Sessions 2026, New Orleans, LA. March 28-30, 2026.

Marston NA, Bohula EA, Bhatia AK, et al. Evolocumab to Reduce First Major Cardiovascular Events in Patients Without Known Significant Atherosclerosis and With Diabetes: Results From the VESALIUS-CV Trial. 

Videos

Marston discusses his sub analysis of the VESALIUS-CV trial, which indicated reduced MACE risk in patients with diabetes and no atherosclerosis after evolocumab treatment.

Olezarsen Proves Efficacy in Severe Hypertriglyceridemia, With Nicholas Marston, MD

The phase 3 CORE and CORE2 trials have highlighted the efficacy of olezarsen in patients with 

 by triggering a highly significant mean reduction in fasting triglyceride levels at 6 months and sustaining it through 12.

Data from both trials were presented at the 

American Heart Association’s Scientific Sessions 2025

 in New Orleans, Louisiana, by Nicholas Marston, MD, cardiologist and assistant professor of medicine at Brigham and Women’s Hospital. The editorial team at 

 sat down with Marston to discuss the implications of these data for cardiovascular care, as well as next steps for olezarsen as indicated in the MRI substudy.

“At this point, we’re not seeing a clinical context here, just an imaging finding,” Marston told 

. “We’re following this over time in the open-label extension, to see if this is something that plateaus. Ultimately, I think it will be something we’ll learn more about, and we’ll keep an eye on it.”

Olezarsen, an investigative antisense oligonucleotide in testing for sHTG treatment, is designed to lower apoC-III production. This protein regulates triglyceride metabolism in the blood, slowing triglyceride clearance and the liver’s uptake of triglyceride-rich particles. Although it has already received approval for chylomicronemia syndrome in the US and EU, its safety and efficacy have not been established for sHTG.

CORE and CORE2 were each double-blind, randomized, placebo-controlled trials by the full names CORE-TIMI 72a and CORE2-TIMI 72b. The primary endpoint in both trials was percent change from baseline in triglycerides at 6 months. Secondary lipid outcomes included the percent change from baseline in triglyceride at 12 months and in apo-C III, remnant cholesterol, and non-HDL-C levels at 6 and 12 months. Additionally, investigators assessed acute pancreatitis events across both trials.

A total of 1063 patients with sHTG were included overall, with 617 in the CORE trial and 446 in the CORE2 trial. They were then randomly assigned in a 1:1:1 ratio to either olezarsen 50 mg, olezarsen 80 mg, or placebo, all of which were administered monthly for 12 months. Both trials included an MRI substudy, assessing changes in hepatic fat at 1 year. The median age across both trials was 54 years, and median baseline triglyceride level was 796 mg/dL.

At 6 months, Marston and colleagues found a placebo-adjusted least-squares mean change in triglyceride level of -62.9 percentage points in the olezarsen 50 mg arm and of -72.2 percentage points in the olezarsen 80 mg arm in the CORE trial. By comparison, mean triglyceride level change in CORE2 was -49.2 percentage points in olezarsen 50 mg and -54.5 percentage points in olezarsen 80 mg.

The team also documented greater decreases in triglyceride, apoC-III, remnant cholesterol, and non-HDL-C in the olezarsen arms compared to placebo across both studies. Acute pancreatitis incidence was also lower with olezarsen than placebo (mean rate ratio, 0.15; 95% CI, 0.05 to 0.4; 

 <.001). Elevations in liver-enzyme levels and thrombocytopenia were more common in the olezarsen 80 mg arms, and a dose-dependent increase in hepatic fat fractions was noted.

Ultimately, Marston discussed potential applications for olezarsen should it receive approval in sHTG. He addressed its potential as an add-on therapy, but ultimately suggested that its relatively rapid effectiveness may position it as a starting therapy for patients at the highest risk levels.

“I think it could be viewed as an add-on, but I think for the highest risk patients, who have already had pancreatitis, we wouldn’t want to delay in getting them on olezarsen,” Marston said. “I could envision it being the first line for those highest-risk patients.”

Editor's Note: Marston reports disclosures with Amgen, Ionis, Pfizer, Novartis, and AstraZeneca.

Marston N, Bergmark B, Alexander V, et al. Olezarsen in Patients with Severe Hypertriglyceridemia: The CORE-TIMI 72a and CORE2-TIMI 72b Trials. Presented at the American Heart Association’s Scientific Sessions 2025. New Orleans, Louisiana. November 8-10, 2025.

Marston NA, Bergmark BA, Alexander VJ, et al. Olezarsen for managing severe hypertriglyceridemia and pancreatitis risk. New England Journal of Medicine. Published online November 8, 2025. 

Marston discusses the CORE and CORE2 trials, highlighting olezarsen’s success in lowering fasting triglyceride.

Nicholas Marston, MD, MPH

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