Evolocumab reduces risk of major cardiac events in diabetic patients
Aggressive LDL cholesterol lowering with the PCSK9 inhibitor evolocumab can significantly reduce major cardiovascular events in diabetic patients without known atherosclerosis. That was the key takeaway from a late-breaking subgroup analysis of the VESALIUS-CV trial presented at ACC.26 in New Orleans.[1]
Cardiovascular Business spoke with presenter Nicholas Marston, MD, MPH, assistant professor of medicine and cardiologist at Brigham and Women's Hospital. He said the analysis focused on a subset of about 30% of trial participants who had no significant atherosclerotic disease, but did have diabetes. This is a population not typically treated aggressively with advanced lipid-lowering therapies.
“It really is a question of whether there's a benefit here,” Marston explained.
These data, he added, suggest it may be worth a more aggressive approach with this patient population.
Significant reductions in major adverse events
The analysis evaluated cardiovascular outcomes over approximately four-and-a-half years and found substantial benefits. Both primary endpoints, which were each focused on adverse cardiovascular events (MACE), were reduced by 31% in patients receiving evolocumab in addition to standard statin therapy.
Secondary outcomes were also notable. Marston reported a 32% reduction in cardiovascular death and a nominal 24% reduction in all-cause mortality.
He said these results build on the broader VESALIUS-CV findings, presented last year, that showed evolocumab reduced first-time cardiovascular events such as myocardial infarction and stroke.
Expanding PCSK9 use as a prevention treatment in earlier-stage patients
Traditionally, high-risk primary prevention patients with diabetes are treated with statins targeting LDL cholesterol levels below 70 mg/dL. In this study, adding evolocumab lowered LDL levels further, achieving an average of 44 mg/dL.
“I think this expands the type of patients that we should be treating more aggressively to lower LDL cholesterol goals,” Marston said.
The findings also reflect a broader shift in cardiovascular prevention strategies toward both earlier interventions and more intensive lipid lowering.
“For decades we've been going lower and lower with LDL cholesterol and we continue to see benefit. There's really no floor,” Marston noted. “But we're also going earlier and earlier in the disease process.”
Implications for primary care
“These patients aren't typically seen in a cardiology clinic because they don't have significant disease,” Marston said. “So we really need to get primary care physicians comfortable with prescribing PCSK9 inhibitors and being more aggressive about LDL lowering.”
He added that broader education and collaboration between cardiology and primary care will be essential to translating these findings into clinical practice.
The results also underscore the elevated cardiovascular risk faced by diabetic patients, even in the absence of detectable atherosclerosis, and suggest that earlier, more aggressive intervention could help prevent first-time events.
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: [email protected]