The cholesterol-lowering drug evolocumab reduced the risk of major adverse cardiac events by nearly one-third among high-risk diabetic patients without known significant atherosclerosis, according to findings presented at the American College of Cardiology's Annual Scientific Session on Mar. 28.
This development is important because it suggests that intensive LDL-C lowering with evolocumab could benefit a broader population than previously considered, especially for primary prevention in people who have not yet experienced major heart events but are at high cardiovascular risk due to diabetes.
The subgroup analysis was part of the larger VESALIUS-CV trial and involved over 3,600 diabetic patients who did not have diagnosed significant plaque buildup in their arteries. Previous studies had focused on secondary prevention—patients who already suffered heart attacks or strokes—but this research examined whether similar benefits exist for those without prior events. Evolocumab works by blocking the PCSK9 protein, increasing the liver's ability to remove LDL cholesterol from the blood and slowing down atherosclerosis progression.
Among 3,655 participants with diabetes but no known significant atherosclerosis, those receiving evolocumab experienced a 31% lower rate of combined outcomes such as death from coronary heart disease, heart attack or ischemic stroke compared to placebo over a median follow-up of nearly five years. The difference became more pronounced after one year and extended up to around 40%. In addition, patients treated with evolocumab saw marked reductions in LDL-C levels throughout the study period.
Marston said that these results indicate "patients with high cardiovascular risk appear to benefit from more intensive LDL-C-lowering treatment, even without known significant atherosclerosis." He added: "Over the decades, we've moved to lower and lower LDL-C goals, and we've continued to see benefit. Now, we're in this process of moving earlier and earlier in the disease course, and so far we're continuing to see benefit from that approach." Marston also noted that new guidelines recommend targeting even lower LDL-C levels earlier in life for at-risk individuals.
Researchers acknowledged some limitations: some participants may have had undiagnosed heart disease since imaging was not required for enrollment; most were older adults and predominantly White; and only those with diabetes were included. They suggested further studies could determine if similar benefits apply across other populations.
