LDL-c reduction to <70 mg/dL reduces adverse CV and renal outcomes in advanced CKD
In a Taiwanese observational cohort study among statin-treated patients with stage 4 CKD, LDL-c <70 mg/dL was associated with a lower risk of major adverse cardiac and cerebrovascular events compared with LDL-c ≥100 mg/dL.
This summary is based on the publication of Yen CL, Fan PC, Lee CC, et al. - The role of maintaining lower LDL-C level during statin treatment for advanced CKD patients. Atherosclerosis. 2024 Dec;399:119042. doi: 10.1016/j.atherosclerosis.2024.119042
Introduction and methods
Background
Previously, a group of Taiwanese researchers demonstrated that in patients with stage 3 CKD who were treated with statins, LDL-c lowering to <70 mg/dL or 70–99 mg/dL provided similar reductions in the risk of major adverse cardiac and cerebrovascular events (MACCE) and new-onset end-stage renal disease (ESRD) compared with LDL-c ≥100 mg/dL [1]. It is uncertain whether LDL-c reduction achieved with statin therapy provides comparable CV benefits in patients with advanced CKD (stages 4–5) and whether a lower LDL-c target should be set as eGFR declines.
Aim of the study
As the second phase of their research project, the same research group investigated the CV and renal protective effects of maintaining a lower LDL-c level in statin-treated patients with stage 4 CKD, stratified by post-treatment LDL-c levels.
Methods
In an observational cohort study, data from 5367 adult patients newly-diagnosed with stage 4 CKD (eGFR 15–29 mL/min/1.73 m²) and receiving statin therapy were extracted from the Chang Gung Research Database, which is Taiwan’s largest healthcare group. Patients with a history of CVD or renal replacement therapy were excluded. Propensity scores with estimated using generalized boosted modeling–inverse probability of treatment weighting.
Outcomes
The primary endpoint was the incidence of MACCE, a composite outcome of acute MI (AMI), ischemic stroke, or CV death. Secondary endpoints were all-cause mortality, CV death, ischemic stroke, AMI, intracerebral hemorrhage, and new-onset ESRD requiring chronic dialysis.
Main results
- At 5-year follow-up, patients with LDL-c <70 mg/dL (n=1139) had a lower risk of MACCE than those with ≥100 mg/dL (n=2467) (14.3% vs. 18.7%; HR: 0.77; 95%CI: 0.69–0.86).
- The group with LDL-c <70 mg/dL also exhibited reduced risks of CV death (7.1% vs. 9.7%; subdistribution HR (SHR): 0.75; 95%CI: 0.65–0.88), ischemic stroke (4.1% vs. 5.4%; SHR: 0.65; 95%CI: 0.54–0.79), and new-onset ESRD requiring chronic dialysis (25.6% vs. 29.4%; SHR: 0.87; 95%CI: 0.80–0.95) but not AMI (5.9% vs. 6.8%; SHR: 0.89; 95%CI: 0.75–1.06) or all-cause mortality (28.5% vs. 30.1%; HR: 0.97; 95%CI: 0.89–1.05) compared with the group with LDL-c ≥100 mg/dL.
- No differences were observed between patients with LDL-c 70–99 mg/dL (n=1761) and those with LDL-c ≥100 mg/dL for any of the endpoints.
- A Cox proportional-hazards model with LDL-c level as a restricted cubic spline showed a predominantly linear association between LDL-c levels and MACCE risk (P for linearity<0.001).
Conclusion
This Taiwanese observational cohort study among statin-treated patients with advanced CKD demonstrated that LDL-c <70 mg/dL was associated with lower risks of adverse CV and renal outcomes compared with LDL-c ≥100 mg/dL. These beneficial effects were not found for LDL-c 70–99 mg/dL. The authors conclude that “[when combining] this study with our previous investigation involving patients with moderate CKD, it appears appropriate to maintain lower LDL-c levels as CKD advances to ensure effective cardiovascular protection, [although] the findings of this study warrant additional validation through prospective studies.”
Reference
- C.L. Yen, P.C. Fan, C.C. Lee, et al., Association of low-density lipoprotein cholesterol levels during statin treatment with cardiovascular and renal outcomes in patients with moderate chronic kidney disease, J. Am. Heart Assoc. 11 (19) (2022) e027516, https://doi.org/10.1161/JAHA.122.027516.