Recent US guidelines have controversially recommended lowering the low-density lipoprotein cholesterol (LDL-C) target to <55 mg/dL for patients with established atherosclerotic cardiovascular disease (ASCVD).¹˒² The Ez-PAVE trial is the first randomised study to directly compare this intensive target with a conventional target of <70 mg/dL. The findings were published in The New England Journal of Medicine.¹
Methodology
The open-label, superiority trial, conducted across multiple centres in South Korea, randomised 3,048 patients with established ASCVD in a 1:1 ratio.¹ Participants were assigned to either an intensive-targeting group (LDL-C <55 mg/dL) or a conventional-targeting group (LDL-C <70 mg/dL). The mean age of participants was 64 years, 79% were male, and over 90% were on a statin at baseline. Treatment to achieve the LDL-C goals was pragmatic and at the discretion of the treating clinicians, with guidance to intensify statin therapy or add ezetimibe or a PCSK9 inhibitor as needed. The primary endpoint at 3 years was a composite of death from cardiovascular (CV) causes, nonfatal myocardial infarction (MI), nonfatal stroke, any revascularisation, or hospitalisation for unstable angina.
Results
After a median follow-up of 3.0 years, the median LDL-C level achieved was 56 mg/dL in the intensive-targeting group and 66 mg/dL in the conventional-targeting group.¹ The primary endpoint occurred in 100 patients (6.6%) in the intensive group compared to 147 patients (9.7%) in the conventional group. This equated to a 33% lower relative risk (hazard ratio [HR], 0.67; 95% CI, 0.52 to 0.86; P=0.002), with a number needed to treat of 32. The main driver of this composite result was a significant reduction in any revascularisation (4.8% vs 7.5%; HR, 0.63). While the rate of MI was slightly lower in the intensive arm (0.8% vs 1.7%), rates of CV death and all-cause death were not significantly different between the groups. The incidence of prespecified safety endpoints was similar in both arms, with the exception of a lower incidence of creatinine elevation in the intensive-targeting group.
Interpretation
The results suggest that in this patient population, a more aggressive LDL-C lowering strategy provides additional cardiovascular benefit, primarily by reducing the need for revascularisation procedures. "Among patients with atherosclerotic cardiovascular disease, targeting an LDL cholesterol level of less than 55 mg per deciliter resulted in a lower risk of cardiovascular events at 3 years than targeting a level of less than 70 mg per deciliter," concluded the Ez-PAVE Investigators.¹
Next Steps
As this trial was conducted in a specific East Asian population, further confirmatory trials in more diverse populations and geographies may be needed to generalise these findings and solidify the recommendation for a lower LDL-C target for all patients with established ASCVD.²
This study was funded by the Cardiovascular Research Center and Yuhan.
References
1. Lee YJ, Lee SJ, Kim JW, et al, for the Ez-PAVE Investigators. Intensive LDL Cholesterol Targeting in Atherosclerotic Cardiovascular Disease. N Engl J Med 2026;394:1365-1375. https://doi.org/10.1056/NEJMoa2600283
2. Mandrola JM. Does Ez-PAVE Support ‘Lower Is Better’ for LDL-C?. Medscape. 2026. https://www.medscape.com/viewarticle/does-ez-pave-support-lower-better-ldl-c-2026a1000akx
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