The benefit of LDL-C levels below 55 mg/dL in ESKD patients under statin treatment: A target trial emulation study

Achieving optimal low-density lipoprotein cholesterol (LDL-C) levels through statin therapy is a cornerstone of cardiovascular disease (CVD) prevention. However, its benefit in end-stage kidney disease (ESKD) remains uncertain, largely because two major randomized controlled trials-4D Study and AURORA Trial-did not demonstrate clear benefits. Notably, the achieved LDL-C levels in these trials remained above current targets for very high-risk populations. We aimed to evaluate whether achieving very low LDL-C levels is associated with improved outcomes in ESKD patients.

We conducted a sequential analysis within a target trial emulation framework using data from the Chang Gung Research Database. ESKD patients receiving maintenance hemodialysis were identified each November from 2014 through 2018. Eligible patients receiving statin therapy (n = 3431) were categorized into four groups according to LDL-C levels at the index examination: <55 mg/dL (n = 623), 55-74 mg/dL (n = 841), 75-99 mg/dL (n = 913), and ≥100 mg/dL (n = 1054).

In multivariable Cox proportional hazards models, patients with LDL-C <55 mg/dL had a significantly lower risk of cardiovascular death compared with LDL-C ≥100 mg/dL (HR 0.71; 95% [CI], 0.53-0.95). A non-significant trend toward reduced all-cause mortality was also observed in the LDL-C <55 mg/dL group. Restricted cubic spline analyses demonstrated an association between lower LDL-C levels and reduced risks of both all-cause mortality and cardiovascular death.

LDL-C <55 mg/dL was associated with lower cardiovascular mortality in ESKD, supporting further investigation into very low LDL-C targets in this population.