Ez-PAVE
(2026)Objective
To evaluate whether targeting an LDL cholesterol level of less than 55 mg/dL is superior to targeting a level of less than 70 mg/dL for preventing recurrent major cardiovascular events in patients with atherosclerotic cardiovascular disease.
Study Summary
• Nonfatal MI occurred in 0.8% vs. 1.7% (HR 0.46, 95% CI 0.23-0.91)
• Any revascularization occurred in 4.8% vs. 7.5% (HR 0.63, 95% CI 0.47-0.84)
• Median LDL cholesterol achieved was 56 mg/dL in intensive-targeting group vs. 66 mg/dL in conventional-targeting group
• No significant differences in safety outcomes except lower creatinine elevation in intensive-targeting group (1.2% vs. 2.7%, p=0.004)
Intervention
LDL cholesterol targeting strategies: <55 mg/dL (intensive) vs. <70 mg/dL (conventional) using statins, ezetimibe, and PCSK9 inhibitors
Inclusion Criteria
Age 19-80 years with documented atherosclerotic cardiovascular disease (previous ACS, stable angina, coronary/arterial revascularization, stroke/TIA, or peripheral artery disease)
Study Design
Arms: Intensive targeting (<55 mg/dL LDL-C) vs. Conventional targeting (<70 mg/dL LDL-C)
Patients per Arm: 1526 (intensive) vs. 1522 (conventional)
Outcome
• Nonfatal MI: 0.8% vs. 1.7% (HR 0.46, 95% CI 0.23-0.91)
• Any revascularization: 4.8% vs. 7.5% (HR 0.63, 95% CI 0.47-0.84)
• Composite of CV death, MI, or stroke: 2.3% vs. 3.6% (HR 0.63, 95% CI 0.41-0.96)
• Safety profile similar between groups except lower creatinine elevation with intensive targeting
Bottom Line
In patients with atherosclerotic cardiovascular disease, targeting an LDL cholesterol level of less than 55 mg/dL resulted in a 33% lower risk of cardiovascular events at 3 years compared to targeting less than 70 mg/dL (HR 0.67, 95% CI 0.52-0.86, p=0.002), with similar safety profiles except for lower creatinine elevation in the intensive-targeting group.
Major Points
- Primary composite endpoint (cardiovascular death, nonfatal MI, nonfatal stroke, any revascularization, or hospitalization for unstable angina) occurred in 6.6% of intensive-targeting group vs. 9.7% of conventional-targeting group at 3 years (HR 0.67, 95% CI 0.52-0.86, p=0.002)
- Median LDL cholesterol achieved during trial was 56 mg/dL in intensive-targeting group vs. 66 mg/dL in conventional-targeting group
- Nonfatal MI occurred in 0.8% vs. 1.7% (HR 0.46, 95% CI 0.23-0.91)
- Any revascularization occurred in 4.8% vs. 7.5% (HR 0.63, 95% CI 0.47-0.84)
- At 3 years, 60.8% of intensive-targeting group achieved LDL <55 mg/dL, and 85.2% achieved <70 mg/dL
- At 3 years, 48.4% of intensive-targeting group received high-intensity statins, 66.6% received ezetimibe, and 2.3% received PCSK9 inhibitors
- No significant differences in safety outcomes except lower creatinine elevation in intensive-targeting group (1.2% vs. 2.7%, p=0.004)
- Similar incidence of new-onset diabetes, muscle symptoms, cancer diagnosis, and liver enzyme elevation between groups
Study Design
- Study Type
- Randomized controlled trial
- Randomization
- Yes
- Blinding
- Open-label
- Sample Size
- 3048
- Follow-up
- Median 3.0 years (IQR 3.0-3.0)
- Centers
- 17
- Countries
- South Korea
Primary Outcome
Definition: Composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, any revascularization, or hospitalization for unstable angina
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 147 patients (9.7% cumulative incidence) | 100 patients (6.6% cumulative incidence) | 0.67 (0.52-0.86) | 0.002 |
Limitations & Criticisms
- Open-label design may introduce bias, though endpoint adjudication was blinded
- Actual number of primary endpoint events was lower than anticipated in sample size calculation
- Only 60.8% of intensive-targeting group reached target LDL <55 mg/dL at 3 years
- Limited use of PCSK9 inhibitors (only 2.3% at 3 years in intensive-targeting group) due to reimbursement constraints
- Other nonstatin agents (inclisiran, bempedoic acid) were unavailable during trial period
- LDL cholesterol levels analyzed without imputation for missing data, potentially introducing bias
- 3-year follow-up may be insufficient to evaluate long-term effects
- Trial conducted only in East Asian patients, limiting generalizability to other populations
- 39% of intensive-targeting group did not reach target at 3 years, suggesting real-world implementation challenges
Citation
N Engl J Med 2026;394:1365-75