Highlights of Cardiovascular Disease Prevention Studies Presented at the 2026 American College of Cardiology Conference.

PURPOSE OF REVIEW: To summarize key findings from cardiovascular disease prevention trials at the 2026 American College of Cardiology (ACC) Conference.

RECENT FINDINGS: The Ez-PAVE trial demonstrated that targeting low-density lipoprotein cholesterol (LDL-C) levels < 55 mg/dL significantly reduces major adverse cardiovascular events compared with a target of < 70 mg/dL in patients with established atherosclerotic cardiovascular disease (ASCVD). A subgroup analysis of the VESALIUS-CV trial showed that Evolocumab reduced first cardiovascular events in high-risk individuals with diabetes who did not have known significant atherosclerosis. The CORALreef AddOn trial demonstrated the superior LDL-C-lowering efficacy of the oral PCSK9 inhibitor Enlicitide compared with ezetimibe, bempedoic acid, and the combination of the two. The Ez-PAVE trial demonstrated that targeting low-density lipoprotein cholesterol (LDL-C) levels < 55 mg/dL significantly reduces major adverse cardiovascular events compared with a target of < 70 mg/dL in patients with established atherosclerotic cardiovascular disease (ASCVD). A subgroup analysis of the VESALIUS-CV trial showed that Evolocumab reduced first cardiovascular events in high-risk individuals with diabetes who did not have known significant atherosclerosis. The CORALreef AddOn trial demonstrated the superior LDL-C-lowering efficacy of the oral PCSK9 inhibitor Enlicitide compared with ezetimibe, bempedoic acid, and the combination of the two. Imaging and diagnostic advances were highlighted by the GPS-CAD study, which demonstrated variability in the reliability of a coronary artery calcium score (CACS) of zero across diverse populations. In contrast, the Essence-TIMI 73b substudy found no significant impact of triglyceride lowering with olezarsen on coronary plaque progression over 12 months. Lifestyle and health equity-focused interventions, including the GoFreshRx and THRIVE trials, demonstrated meaningful reductions in blood pressure through dietary and food-as-medicine strategies in underserved populations. Additionally, the SURPASS-CVOT post hoc analysis showed that tirzepatide reduced composite cardiorenal outcomes compared with dulaglutide in patients with type 2 diabetes. Finally, the SMART-DECISION trial suggested that discontinuation of beta-blockers in stable patients one year after myocardial infarction with an LVEF of at least 40% may be safe and noninferior to continuation. The studies presented at ACC 2026 emphasize the importance of intensive lipid-lowering strategies, expand the use of new cardiometabolic therapies, and showcase emerging diagnostic and preventive strategies for ASCVD.