More intensive use of lipid-lowering drugs to reach a lower target for low-density lipoprotein cholesterol (LDL-C) reduced the rate of major cardiovascular (CV) events by one third among people with atherosclerotic CV disease (ASCVD), according to a study in South Korea.

Recent updates to clinical guidelines lowered the LDL-C target from < 70 mg/dL to < 55 mg/dL for people with ASCVD at high or very high risk for a CV event, but those updates were based on limited evidence that did not specifically evaluate different targets.

Byeong-Keuk Kim, MD, director of the Cardiac Catheterization and Intervention Department at Severance Cardiovascular Hospital, Yonsei University College of Medicine in Seoul, Republic of Korea, conducted the Ez-PAVE study to evaluate whether the lower target is indeed better.

Kim and colleagues assigned more than 3000 patients with ASCVD at high or very high risk for another event to either the lower intensive target or the conventional higher target. Treatment followed standard medical guidelines using statins and other medications such as ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

After 3 years, patients in the intensive group had a median LDL-C level of 56 mg/dL, with 39% failing to achieve the target. Those in the conventional group had a median level of 66 mg/dL. But the intensive group had a 33% reduction in risk for the composite primary endpoint of CV death, nonfatal myocardial infarction, nonfatal stroke, any revascularization, or hospitalization for unstable angina (hazard ratio, 0.67; 95% CI, 0.52-0.86).

“The Ez-PAVE trial adds practical and clinically meaningful evidence by demonstrating that, in patients with ASCVD, targeting an LDL cholesterol level of less than 55 mg/dL leads to a significantly lower 3-year risk of major cardiovascular events compared with the conventional target of 70 mg/dL, without compromising safety,” Kim said in a news release.

The work was presented at the American College of Cardiology (ACC) Scientific Session 2026 and published simultaneously in The New England Journal of Medicine.

Strength of Existing Therapies

Michael Shapiro, DO, director of the Center for Preventive Cardiology at Wake Forest Baptist Health in Winston-Salem, North Carolina, said the study’s direct support for lower targets through a randomized trial was important.

And since new drugs such as inclisiran were not available in South Korea during the study period, and the use of PCSK9 inhibitors is limited there due to reimbursement policies, it shows what can be done using more traditional lipid-lowering therapies.

“To me, one of the most practical aspects of the trial is that the lower target was achieved mostly with statins and ezetimibe, not with heavy reliance on PCSK9 inhibitors,” said Shapiro, who was not involved with the study. “This shows that clinicians can often push LDL cholesterol lower with therapies that are already familiar and accessible.”

Cautious Interpretation

The study did have some limitations. It was open-label, as clinicians needed to know what target they were aiming for, and was conducted in an entirely East Asian population, potentially limiting its wider applicability. The difference in achieved LDL-C levels between the two groups was also modest, but the reduction in risk was larger than would be expected for that difference — and the reason for this discrepancy is not entirely clear.

“I would view Ez-PAVE as strong supportive evidence for lower LDL cholesterol goals in secondary prevention, not as a reason to ignore clinical judgment or pretend the question is completely settled in every population,” Shapiro said.

Kim reported receiving consulting fees from Amgen, AstraZeneca, DIO Medical, Hanmi, and Novartis. Shapiro reported having no relevant financial relationships.

Brian Owens is a freelance journalist based in New Brunswick, Canada.