Lowering LDL-C to <55 mg/dL in patients with atherosclerotic cardiovascular disease (ASCVD) reduced the rate of major cardiovascular events by one-third, according to the Ez-PAVE trial presented during a Late-Breaking Clinical Trials session at ACC.26 in New Orleans and simultaneously published in NEJM.

Ez-PAVE is the first randomized, head-to-head comparison of the effects of two LDL-C targets in patients with ASCVD. The trial was conducted from January 2021 through July 2022 at 17 sites in South Korea. Of 3,048 patients enrolled, 1,526 were assigned to an intensive-target group of <55 mg/dL and 1,522 to a conventional-target group of <70 mg/dL. The mean age of the patients was 64 years and 21% were women. ASCVD was defined as having a previous acute coronary syndrome, stable angina with imaging or functional studies, coronary revascularization or other arterial revascularization, stroke or transient ischemic attack or peripheral artery disease.

At three years, patients in the intensive group had a median LDL-C of 56 mg/dL vs. 66 mg/dL in the conventional group. Reflecting real-world clinical practice, treatment decisions were at the clinician’s discretion, following treatment guidelines including the use of high-intensity statin therapy and adding other medications, such as ezetimibe and PCSK9 inhibitors as needed.

The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, any revascularization or hospitalization for unstable angina. Results showed that at three years, the primary composite endpoint occurred in 6.6% (n=100) of patients in the intensive group and 9.7% (n=147) of the conventional group, a 33% reduction in risk in favor of the more aggressive target. This benefit was driven primarily by a reduction in nonfatal MI and revascularization. The composite of cardiovascular death, MI or stroke also was significantly lower in the intensive group (2.3% vs. 3.6%).

The safety profile was similar across groups.

The study was not blinded because the treating clinicians needed to know the LDL-C target for each patient. In addition, it was conducted in South Korea and all patients were from East Asia, potentially limiting the application to other countries or racial and ethnic groups that may see different disparities in cardiovascular risk or different patterns of therapy to reduce LDL-C levels. Researchers also noted that newer nonstatin therapies including inclisiran and bempedoic acid were not available in South Korea and use of PSCK9 inhibitors was limited because of reimbursement policies. In the intensive group, 39% of patients did not reach the target of <55 mg/dL.

“The Ez-PAVE trial adds practical and clinically meaningful evidence by demonstrating that, in patients with ASCVD, targeting an LDL-C level of <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,” says Byeong-Keuk Kim, MD, PhD, lead author of the trial.

In a related editorial comment, Jeffrey L. Probstfield, MD, and Kelley R.H. Branch, MD, FACC, add, “The Ez-PAVE trial firms the foundation of lipid guidelines in secondary prevention and potentially paves the way for more definitive trials to evaluate targeted LDL-C levels in other populations, with other treatment combinations, and with other LDL-C goals for primary prevention.”

Clinical Topics: Prevention

Keywords: ACC Annual Scientific Session, ACC26, New Orleans, Dyslipidemia, Republic of Korea, Primary Prevention