Targeting less than 55 mg/dL, rather than 70 mg/dL, for LDL-C reduced risk of major events in patients with atherosclerotic cardiovascular disease

NEW ORLEANS (March 28, 2026) — Using cholesterol-lowering medications more intensively to achieve a more aggressive target for low-density lipoprotein cholesterol (LDL-C) reduced the rate of major cardiovascular events by one-third among patients with atherosclerotic cardiovascular disease (ASCVD), according to a study presented at the American College of Cardiology’s Annual Scientific Session (ACC.26).

The results help fill an evidence gap in guiding treatment for patients with heart disease who face a high risk of serious cardiac events. Although guidelines have lowered the recommended LDL-C target for patients with ASCVD from less than 70 mg/dL to less than 55 mg/dL, the evidence supporting this recommendation has been limited. The new trial, called Ez-PAVE, is the first randomized, head-to-head comparison of these two LDL-C targets in patients with ASCVD.

“The Ez-PAVE trial adds practical and clinically meaningful evidence by demonstrating that, in patients with ASCVD, targeting an LDL-C level of less than 55 mg/dL leads to a significantly lower three-year risk of major cardiovascular events compared with the conventional target of 70 mg/dL, without compromising safety,” said Byeong-Keuk Kim, MD, director of the Cardiac Catheterization and Intervention Department and professor in the Division of Cardiology at Severance Hospital, Yonsei University College of Medicine in Seoul, South Korea, and the study’s lead author.

ASCVD is a type of heart disease in which plaque accumulates in artery walls. LDL-C contributes to plaque buildup. Therapies that reduce LDL-C can help slow the buildup of plaque in the artery walls and reduce the likelihood that plaques will rupture and cause serious events such as heart attacks and strokes. However, most previous studies have focused on assessing outcomes from various LDL-C lowering therapies rather than assessing the optimal LDL-C level to target with these therapies, Kim said.

Researchers enrolled 3,048 patients at 17 sites in South Korea. Participants were 64 years old, on average, and 21% were women. All participants had ASCVD, defined as having had prior acute coronary syndrome, stable angina with objective evidence, a procedure to open blocked arteries (revascularization), stroke or transient ischemic attack, or peripheral artery disease. Overall, the study cohort reflects a high- to very high-risk population based on their high prevalence of prior acute coronary syndrome, revascularization and diabetes, according to the researchers.

Half of the patients were randomly assigned to an LDL-C target of less than 55 mg/dL and half were assigned to target less than 70 mg/dL. At three years, patients in the first group had a median of 56 mg/dL LDL-C, and those in the second group had a median of 66 mg/dL. To achieve these LDL-C targets, treating clinicians followed medical guidelines by increasing the intensity of statin therapy and adding other medications such as ezetimibe and PCSK9 inhibitors when needed. Treatment decisions including dose adjustments, the addition of different therapies, and the management of adverse effects were left to the clinician’s discretion to reflect real-world clinical practice.

The study’s primary endpoint was a composite of cardiovascular death, nonfatal heart attack, nonfatal stroke, any revascularization or hospitalization for unstable angina (chest pain or tightness). At three years this composite endpoint occurred in 6.6% of those assigned to a target of less than 55 mg/dL LDL-C and 9.7% of those assigned to target 70 mg/dL, a 33% reduction in risk in favor of the more aggressive target. This benefit was driven primarily by a reduction in nonfatal heart attacks and revascularization. The composite of cardiovascular death, heart attack or stroke was also significantly lower in the more intensive-targeting group (2.3% vs. 3.6%).

“The consistency across the overall population and key subgroups suggests that the benefit of targeting LDL-C lower than 55 mg/dL is broadly applicable across the spectrum of patients with ASCVD and is not limited to specific patient subsets,” Kim said, noting that the findings are especially relevant for patients in higher-risk categories, for whom lower LDL-C targets are currently recommended.

The two study groups showed a similar safety profile, with no significant differences in the incidence of muscle symptoms, new-onset diabetes or worsening of glycemic control among those with diabetes. Elevation of creatinine (an indicator of worsening kidney function) was less frequent in the intensive-targeting group, and researchers said that future studies could help elucidate whether more intensive LDL-C lowering could help slow kidney disease progression.

The study was not blinded because the treating clinicians needed to know what LDL-C level to target for each patient. In addition, the trial was conducted entirely in South Korea, and all participants were from East Asia, potentially limiting applicability to other countries or racial and ethnic groups that may see different disparities in cardiovascular risk or different patterns of LDL-C lowering therapy.

Kim also said that in the more intensive-targeting group, 39% of patients never achieved the target of less than 55 mg/dL LDL-C. During the study period, newer non-statin cholesterol-lowering therapies including inclisiran and bempedoic acid were not available in South Korea, and the use of PCSK9 inhibitors was generally limited due to reimbursement policies. Kim said that more intensive use of such non-statin therapies may have resulted in lower achieved LDL-C levels and possibly greater clinical benefit. Additional studies could assess the effects of more intensive use of such therapies.

The study was funded by the Cardiovascular Research Center under a contract with Yuhan Corporation.

This study was simultaneously published online in the New England Journal of Medicine at the time of presentation.

Kim will present the study, “Intensive Low-density Lipoprotein Cholesterol Targeting in Patients with Atherosclerotic Cardiovascular Disease,” on Saturday, March 28, at 3:45 p.m. CT / 20:45 UTC in the Main Tent, Great Hall.

ACC.26 will take place March 28-30, 2026, in New Orleans, bringing together cardiologists and cardiovascular specialists from around the world to share the newest discoveries in treatment and prevention. Follow @ACCinTouch, @ACCMediaCenter and #ACC26 for the latest news from the meeting.

The American College of Cardiology (ACC) is the global leader in transforming cardiovascular care and improving heart health for all. As the preeminent source of professional medical education for the entire cardiovascular care team since 1949, ACC credentials cardiovascular professionals in over 140 countries who meet stringent qualifications and leads in the formation of health policy, standards and guidelines. Through its world-renowned family of JACC Journals, NCDR registries, ACC Accreditation Services, global network of Member Sections, CardioSmart.org patient resources and more, the College is committed to ensuring a world where science, knowledge and innovation optimize patient care and outcomes. Learn more at ACC.org.

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