Marc Bonaca, MD, MPH, is the executive director at CPC Clinical Research, director of vascular research at the University of Colorado Anschutz, and a cardiologist with Brigham and Women’s Hospital and the VA Boston Healthcare System.

Marc P. Bonaca, MD, MPH

The phase 3 VESALIUS-CV trial has shown that evolocumab protects against cardiovascular disease in at-risk patients with 

 prior to screening, hinting at a new treatment pathway for cardiovascular disease.

VESALIUS-CV: Evolocumab Prevents Cardiovascular Disease in High-Risk Diabetes

These data were discussed at the American Society for Preventive Cardiology (ASPC) 2026 Congress on Cardiovascular Disease Prevention in Scottsdale, Arizona, by Marc Bonaca, MD, MPH, executive director at CPC Clinical Research, director of vascular research at the University of Colorado Anschutz, and a cardiologist with Brigham and Women’s Hospital and the VA Boston Healthcare System.

“VESALIUS moved backward in terms of risk,” Bonaca told 

 in an exclusive interview. “It included patients who were either at high risk without known 

, or those who had it but who had not yet had an event. VESALIUS really asked the question of whether PCSK9 inhibition benefits patients who are at high risk or have the disease but haven’t yet experienced an event.”

VESALIUS-CV was a double-blind, randomized, placebo-controlled, multicenter phase 3 study examining evolocumab’s impact on MACEs in patients at high cardiovascular risk without prior MI or stroke. The study was conducted across 852 locations worldwide and ultimately enrolled over 6000 patients. To be eligible for inclusion, patients needed to be aged at least 50 years (men) or at least 55 years (women) and less than 80 years and have LDL-C greater than or equal to 90 mg/dL, non-HDL-C greater than or equal to 120 mg/dL, or apolipoprotein B greater than or equal to 80 mg/dL. Additionally, patients were required to meet at least 1 of the following at screening:

Significant coronary artery disease (CAD)

Significant atherosclerotic cerebrovascular disease

Patients were excluded from the trial if they had experienced an MI or stroke prior to randomization, had undergone coronary artery bypass grafting (CABG) less than 3 months before surgery, or eGFR less than 15 mL/min/1.73m

, among other criteria. The primary outcomes were the number of patients experiencing coronary heart disease (CHD), MI, or ischemic stroke, whichever occurred first, as well as the number of patients experiencing CHD death, MI, ischemic stroke, or any ischemia-driven arterial revascularization, whichever occurred first.

The team ultimately enrolled 6002 patients with high-risk diabetes. Of these, 67% were on a high-intensity statin, and 24% were on an SGLT2 inhibitor or a GLP-1 receptor agonist at baseline. Median LDL-C at 48 weeks was 47 mg/dL and 109 mg/dL in the evolocumab and placebo arms, respectively (

Following a median follow-up of 4.6 years, evolocumab was found to have decreased the relative rates of 3-point MACE and 4-point MACE by 29% (HR, 0.71; 95% CI, 0.59-0.86; 

 = .0004) and 21% (HR, 0.79; 95% CI, 0.69-0.91; 

 = .0013), respectively. Additionally, these findings were consistent irrespective of the presence or absence of atherosclerosis, baseline LDL-C, statin treatment intensity, and SGLT2 inhibitor or GLP-1 RA use. Investigators noted that the proportion of patients with all-cause mortality was 8.8% in the evolocumab arm vs 11% in the placebo arm (HR, 0.79; 95% CI, 0.67-0.93).

Ultimately, investigators concluded that evolocumab effectively reduced the rate of cardiovascular events in this patient cohort, regardless of the background use of other protective agents or the presence or absence of qualifying atherosclerosis.

“The field is shifting as we become much more sophisticated about understanding atherosclerosis,” Bonaca said. “If you think about it, for cancer screenings, we don’t wait for people to become symptomatic to treat them, and we don’t treat them based on guessing whether or not they have disease. We image—we conduct colonoscopies, mammograms, biopsies, and we treat accordingly. And for the No. 1 killer in the world, cardiovascular disease, we now have tools that allow a much more sophisticated approach.”

Editors’ Note: Bonaca reports disclosures with Abbott, Amgen, BMS, Merck, Novo Nordisk, Sanofi, and others.

Leiter LA, Giugliano RP, Marston NA, et al. Evolocumab in patients with high-risk diabetes: results from the Vesalius-CV trial. 

Effect of evolocumab in patients at high cardiovascular risk without prior myocardial infarction or stroke (VESALIUS-CV). ClinicalTrials.gov Identifier: NCT03872401. Updated June 25, 2026. Accessed August 27, 2026. 

https://clinicaltrials.gov/study/NCT03872401

Videos

The phase 3 trial of evolocumab showed cardioprotective effects in patients without prior MI or stroke, regardless of qualifying atherosclerosis or background therapy.

Semaglutide Boosts PAD Outcomes in STRIDE with Marc Bonaca, MD, MPH

Results from the Phase 3b STRIDE trial suggest semaglutide 1.0 mg (Ozempic) could be the first therapy in nearly two decades to gain regulatory approval for improving functional outcomes in 

American College of Cardiology (ACC) 2025 Annual Scientific Sessions

, semaglutide benefited walking distance, quality of life, and ankle-brachial index in patients with PAD and type 2 diabetes (T2D). With currently limited PAD treatment options, the only guideline-recommended drug for symptoms is rarely used due to contraindications and side effects. As PAD progresses, patients often require revascularization procedures and face an increased risk of cardiovascular and limb events.

“I think we're seeing now that GLP-1 agonists are vascular drugs, and they do things that other drugs haven't done before,” study investigator Marc Bonaca, MD, MPH, a cardiologist and vascular medicine specialist serving as executive director of CPC and director of vascular research and professor of medicine at the University of Colorado Anschutz, told HCPLive. “This is a paradigm shift for PAD, but it also teaches us more about this class of agents and other things we may think about in the future.”

The Novo Nordisk-funded STRIDE trial enrolled 792 patients across 20 countries, randomizing them 1:1 to semaglutide or placebo for 52 weeks. At the study’s conclusion, semaglutide recipients experienced significantly greater improvements in maximum walking distance compared with placebo (estimated treatment ratio [ETR], 1.13; 95% CI, 1.06–1.21; P=.0004).

Additional analysis showed improvements in median maximum walking distance (ETR, 1.08; 95% CI, 1.00 to 1.16; P = 0.038), pain-free walking distance (ETR, 1.11; 95% CI, 1.03–1.20; P=.0046), and quality-of-life scores (ETR, 1.00; 95% CI, 0.48–1.52; P =.011).

Safety analysis found serious treatment-related adverse events in 1% of the semaglutide group and 2% of the placebo group, with gastrointestinal issues being the most common. No treatment-related deaths were reported.

Semaglutide’s benefits in PAD could be due to a direct vascular effect rather than weight loss, as the study population had a median BMI of 28.6 and a weak correlation between weight loss and outcomes. Future studies may explore whether patients with PAD but without type 2 diabetes could also benefit from semaglutide.

“I think what we found in STRIDE, in terms of significant improvement in every one of the pre-specified secondary endpoints, and the evidence of a direct vascular effect and benefit in the absence of weight loss, really suggests that this is a drug that should work for people who don't have diabetes,” Bonaca told HCPLive. “This needs to be tested in patients with PAD, regardless of diabetes status, similar to what was done in the SELECT trial for outcomes.”

Bonaca reports relevant disclosures with Abbott, Amgen, BMS, Merck, NovoNordisk, Sanofi, and others.

Campbell P. STRIDE: SEMAGLUTIDE improves functional outcomes in peripheral artery disease. HCP Live. March 29, 2025. Accessed April 3, 2025. https://www.hcplive.com/view/semaglutide-improves-functional-outcomes-in-peripheral-artery-disease.

Marc Bonaca, MD, MPH, examines the benefit of semaglutide on functional outcomes in PAD from the STRIDE trial at ACC.25.

Semaglutide Boosts PAD Outcomes in STRIDE with Marc P. Bonaca, MD, MPH

Podcasts

I'm sorry, but it seems there is no article text provided for me to summarize and extract key takeaways from. Could you please provide the text of the article

Panelists discuss how lifestyle interventions, including diet, physical activity, and smoking cessation, complement pharmacotherapy in the management of dyslipidemia, and explore unmet needs in cardiovascular risk reduction, highlighting the role of emerging therapies such as bempedoic acid, inclisiran, and gene editing technologies.

Navigating Lifestyle and Pharmacotherapy Interventions in Dyslipidemia Management  

Exploring Bempedoic Acid: Clinical Indications, Efficacy, and Future Directions in Cardiovascular Risk Management 

Panelists discuss how bempedoic acid offers a promising alternative for patients who are statin-intolerant, demonstrating efficacy in reducing major cardiovascular events and low-density lipoprotein cholesterol, while addressing its role in managing residual cardiovascular risk, particularly in high-risk populations.

Marc P. Bonaca, MD, MPH

Articles