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Published on: January 8, 2020
Statins, Mortality, and Major Adverse Cardiovascular Events Among US Veterans With Chronic Kidney Disease
Odeya Barayev1, Chelsea E Hawley2, Helen Wellman3
1Ben Gurion University of the Negev, Be'er Sheva, Israel.
Insights
Statin use in older veterans with moderate chronic kidney disease (CKD) was linked to reduced all-cause mortality but not major adverse cardiovascular events (MACE). Further research is needed to confirm these findings for atherosclerotic cardiovascular disease (ASCVD) prevention.
Area of Science:
- Nephrology
- Cardiology
- Geriatrics
- Pharmacology
Background:
- Limited data exist on statin efficacy for primary prevention of atherosclerotic cardiovascular disease (ASCVD) and death in chronic kidney disease (CKD) patients.
- Older adults with moderate CKD (stages 3-4) represent a population with high cardiovascular risk and potential benefit from statin therapy.
Purpose of the Study:
- To evaluate the association of statin initiation with all-cause mortality and major adverse cardiovascular events (MACE) in US veterans aged over 65 with CKD stages 3-4.
- To assess the utility of statins for primary ASCVD prevention in this specific high-risk cohort.
Main Methods:
- A target trial emulation design using linked Veterans Affairs, Medicare, and Medicaid data.
- Propensity weighting and Cox proportional hazards models were employed for analysis in a cohort of veterans newly diagnosed with moderate CKD.
- Eligibility criteria included age >65, no prior ASCVD or statin use, and within 5 years of CKD diagnosis.
Main Results:
- Statin initiation was significantly associated with a reduced hazard ratio for all-cause mortality (0.91; 95% CI, 0.85-0.97).
- No significant association was found between statin initiation and the risk of MACE (hazard ratio, 0.96; 95% CI, 0.91-1.02).
- Results were consistent across prespecified subgroup analyses.
Conclusions:
- Statin initiation in older US veterans with moderate CKD and no prior ASCVD was associated with lower all-cause mortality.
- The study did not find a significant association between statin use and reduced MACE in this population.
- Confirmation through a randomized clinical trial is recommended to validate these findings.
Importance:
There are limited data for the utility of statins for primary prevention of atherosclerotic cardiovascular disease (ASCVD) and death in adults with chronic kidney disease (CKD).
Objective:
To evaluate the association of statin use with all-cause mortality and major adverse cardiovascular events (MACE) among US veterans older than 65 years with CKD stages 3 to 4.
Design, Setting, And Participants:
This cohort study used a target trial emulation design for statin initiation among veterans with moderate CKD (stages 3 or 4) using nested trials with a propensity weighting approach. Linked Veterans Affairs (VA) Healthcare System, Medicare, and Medicaid data were used. This study considered veterans newly diagnosed with moderate CKD between 2005 and 2015 in the VA, with follow-up through December 31, 2017. Veterans were older than 65 years, within 5 years of CKD diagnosis, had no prior ASCVD or statin use, and had at least 1 clinical visit in the year prior to trial baseline. Eligibility criteria were assessed for each nested trial, and Cox proportional hazards models with bootstrapping were run. Analysis was conducted from July 2021 to October 2023.
Exposure:
Statin initiation vs none.
Main Outcomes And Measures:
Primary outcome was all-cause mortality; secondary outcome was time to first MACE (myocardial infarction, transient ischemic attack, stroke, revascularization, or mortality).
Results:
Included in the analysis were 14 828 veterans. Mean (SD) age at CKD diagnosis was 76.9 (8.2) years, 14 616 (99%) were men, 10 539 (72%) White, and 2568 (17%) Black. After expanding to person-trials and assessing eligibility at each baseline, there were 151 243 person-trials (14 685 individuals) of nonstatin initiators and 2924 person-trials (2924 individuals) of statin initiators included. Propensity score adjustment via overlap weighting with nonparametric bootstrapping resulted in covariate balance, with mean (SD) follow-up of 3.6 (2.7) years. The hazard ratio for all-cause mortality was 0.91 (95% CI, 0.85-0.97) comparing statin initiators to noninitiators. The hazard ratio for MACE was 0.96 (95% CI, 0.91-1.02). Results remained consistent in prespecified subgroup analyses.
Conclusions And Relevance:
In this target trial emulation of statin initiation in US veterans older than 65 years with CKD stages 3 to 4 and no prior ASCVD, statin initiation was significantly associated with a lower risk of all-cause mortality but not MACE. Results should be confirmed in a randomized clinical trial.
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