CONFERNCE UPDATE: ACC 2026

The Ez-PAVE trial: Intensive LDL-C targeting reduces 3-year CV events in ASCVD patients

CARDIOLOGY
03 Jun 2026

STUDY DESIGN

Recent guidelines recommend more aggressive low-density lipoprotein cholesterol (LDL-C) targets from 70mg/dL to <55mg/dL in patients with atherosclerotic cardiovascular disease (ASCVD) despite historically limited evidence supporting this threshold.1 The Ez-PAVE trial is a multicenter, randomized, open-label study designed to evaluate whether intensive LDL-C targeting (<55mg/dL) is superior to conventional targeting (<70mg/dL) in preventing cardiovascular events in patients with ASCVD.1

A total of 3,048 patients aged 19-80 years with documented ASCVD were enrolled across 17 sites in South Korea.1 ASCVD was defined as the presence of at least one of the following: previous acute coronary syndrome (ACS), stable angina with imaging or functional evidence, prior coronary or other arterial revascularization, stroke or transient ischemic attack (TIA), or peripheral artery disease (PAD).1 Patients were randomized 1:1 to intensive or conventional LDL-C target groups.1 Following randomization, patients in each group were further assigned in a 1:1 ratio to receive either statin monotherapy (rosuvastatin or atorvastatin, allocated in a 1:1 ratio) or statin + ezetimibe combination therapy (rosuvastatin + ezetimibe).1 Lipid-lowering therapy was subsequently titrated to achieve the assigned LDL-C targets, with statin up-titration and addition of ezetimibe recommended prior to initiation of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.1

Baseline characteristics were well-balanced between the two groups, with a mean age of approximately 64 years, and 79% were male.1 Clinical presentations were comparable, including similar proportions of prior ACS, stable angina, previous revascularization, stroke/TIA and PAD.1 Comorbidities, such as diabetes and chronic kidney disease, were also evenly distributed.1 Median baseline LDL-C levels were similar between groups at 75mg/dL-77mg/dL.1

The primary endpoint was the composite of cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, any revascularization, or hospitalization for unstable angina at 3 years.1 Key secondary endpoints included individual components of the primary endpoint and prespecified composite outcomes.1 Safety endpoints evaluated new-onset diabetes, worsening of glycemic control, statin-associated muscle symptoms leading to changes in therapy dose or regimen, cancer diagnosis, cataract surgery, aminotransferase elevation, creatine kinase elevation, and creatinine elevation.1

 

FINDINGS

Primary endpoint:
  • The primary endpoint was the composite of CV death, nonfatal MI, nonfatal stroke, any revascularization, or hospitalization for unstable angina at 3 years1
  • At 3 years, intensive LDL-C targeting significantly reduced the risk of the primary composite endpoint by 33% vs. conventional targeting (6.6% vs. 9.7%; HR=0.67, 95% CI: 0.52-0.86; p=0.002) 1
  • The treatment effect on the primary composite endpoint was consistently maintained across the majority of prespecified subgroups1

Secondary endpoints
  • Key secondary endpoints included individual components of the primary endpoint and prespecified composite outcomes1
  • High-intensity statin monotherapy, high-intensity statin monotherapy + ezetimibe and PCSK9 inhibitor use were consistently higher in the intensive-targeting group1
  • At 3 years, the median LDL-C level was 52mg/dL in the intensive-targeting group (with 60.8% achieving LDL-C <55mg/dL), compared with a median of 66mg/dL in the conventional-targeting group (with 68.1% achieving LDL-C <70mg/dL)1
  • Intensive LDL-C targeting significantly reduced nonfatal MI (HR=0.46; 95% CI: 0.23-0.91; p=0.022), any revascularization (HR=0.63; 95% CI: 0.47-0.84; p=0.002), PCI (HR=0.67; 95% CI: 0.49-0.91; p=0.009) and CABG (HR=0.14; 95% CI: 0.02-1.15; p=0.033). No significant differences were observed for CV death, all-cause death, nonfatal stroke, and hospitalization for unstable angina1
  • Intensive LDL-C targeting also significantly reduced the composite of CV death, nonfatal MI, or nonfatal stroke by 37% at 3 years (HR=0.63; 95% CI: 0.41-0.96; p=0.030) 1

Safety endpoints:
  • Safety endpoints evaluated new-onset diabetes, worsening of glycemic control, statin-associated muscle symptoms leading to changes in therapy dose or regimen, cancer diagnosis, cataract surgery, aminotransferase elevation, creatine kinase elevation, and creatinine elevation1
  • Intensive LDL-C targeting was not associated with an increase in major safety concerns, as overall rates of key safety endpoints were comparable between groups1
  • Laboratory abnormalities were generally similar, although creatinine elevation occurred less frequently in the intensive-targeting group (1.2% vs. 2.7%; p=0.004) 1

 

“Intensive LDL-C targeting <55mg/dL reduced 3-year CV events compared with conventional targeting <70mg/dL, supporting more intensive lipid-lowering strategies for secondary prevention in patients with ASCVD, in line with current guideline recommendations.”

Dr. Byeong-Keuk Kim
Severance Hospital, Yonsei University College of Medicine,
South Korea

 

Get access to our exclusive articles.
Related Articles

Evolocumab reduces first MACE in high-risk patients without established atherosclerosis: Subgroup analysis from the VESALIUS-CV trial

STUDY DESIGN VESALIUS-CV was a randomized, double-blind, placebo-controlled, multicenter trial conducted across 33 countries that enrolled 12,257 patients to evaluate the impact of evolocumab on major adverse cardiovascular events (MACE) in patients at high cardiovascular (CV) risk without prior my
CARDIOLOGY
20 Jul 2026

Refining risk stratification and treatment in dyslipidemia: The 2025 ESC/EAS focused update

Since the release of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) Guidelines on managing dyslipidemias to lower cardiovascular (CV) risk, several randomized controlled trials have emerged that could influence patient management prior to the next comprehensive

CARDIOLOGY
24 Oct 2025

LDL-C reduction with lerodalcibep in patients at very high or high risk for CVD: The phase 3 LIBerate-HR study

STUDY DESIGN Lerodalcibep is a third-generation proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor that prevents PCSK9 from binding to low-density lipoprotein receptors (LDLRs).1 Low-density lipoprotein-cholesterol (LDL-C) clearance from the bloodstream is enhanced as a result of LDLR

CARDIOLOGY
15 Jul 2024

Triglyceride reduction with olezarsen in HTG patients with high CV risk: The BRIDGE-TIMI 73a trial

STUDY DESIGN Triglyceride-rich lipoproteins (TRLs) are atherogenic and increase cardiovascular (CV) risk comparable with low-density lipoprotein (LDL).1 Their clearance is facilitated by lipoprotein lipase (LPL) which hydrolyses the triglyceride (TG) component.1 However, some TRLs express apolipopr
CARDIOLOGY
15 Jul 2024

“Inclisiran first” strategy lowers LDL-C in real-world ASCVD patients: Results from the VICTORION-INITIATE trial

A reduction in LDL-C is associated with improvements in CV outcomes in patients with ASCVD.1 As such, multiple guidelines recommend LDL-C targets of <55mg/dL and <70mg/dL based on baseline risks.1 However, many patients fail their LDL-C goals due to clinical inertia, medication nonadherence, side effects, and/or poor healthcare access.1 Inclisiran is a first-in-class siRNA that inhibits hepatic PCSK9 production and increases LDL receptor expression and LDL-C clearance.1 In clinical studies, twice-yearly administration of inclisiran has been shown to achieve a 50% reduction in LDL-C.1
CARDIOLOGY
08 Jul 2024

Bempedoic acid receives FDA approvaal for expanded indication in CVD Prevention

Bempedoic acid inhibits ATP citrate lyase, an enzyme upstream of 3-hydroxy-3-methalglutaryl-coenzyme (HMG-CoA) reductase which is the rate-limiting step of cholesterol biosynthesis.1,2 This reduces hepatic cholesterol synthesis and raises LDL receptor expression, increasing the clearance of LDL-C fr
CARDIOLOGY
23 Apr 2024

Long-term efficacy and tolerability of inclisiran sustained in ORION-8, the 3-year OLE study, among patients with high CV risk

STUDY DESIGN Inclisiran is a small interfering ribonucleic acid (siRNA) therapeutic, which offers a 52% reduction in low-density lipoprotein cholesterol (LDL-C) after only 18 months of treatment among patients with high cardiovascular (CV) risks.1 Previous phase 3 studies such as ORION-9, ORION-10,
CARDIOLOGY
17 Nov 2023