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Randomized Controlled Trial
. 2023 Dec 1;6(12):e2346373.
doi: 10.1001/jamanetworkopen.2023.46373.

Statins, Mortality, and Major Adverse Cardiovascular Events Among US Veterans With Chronic Kidney Disease

Odeya Barayev  1 , Chelsea E Hawley  2 , Helen Wellman  3 , Hanna Gerlovin  3 , Whitney Hsu  4 , Julie M Paik  2   5   6 , Ernest I Mandel  6 , Christine K Liu  7   8 , Luc Djoussé  3   9 , J Michael Gaziano  3   9 , David R Gagnon  3   10 , Ariela R Orkaby  2   3   9
Affiliations
Randomized Controlled Trial

Statins, Mortality, and Major Adverse Cardiovascular Events Among US Veterans With Chronic Kidney Disease

Odeya Barayev et al. JAMA Netw Open. .

Abstract

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Wellman reported receiving personal fees from Novartis Inc outside the submitted work. Dr Djoussé reported receiving grants from Novartis during the conduct of the study. Dr Gaziano reported receiving grants from Novartis outside the submitted work. Dr Orkaby reported receiving grants from the National Institutes of Health and the Department of Veterans Affairs (VA) as well as personal fees from Anthos Therapeutics during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Association Between Statin Initiation and All-Cause Mortality in US Veterans Older Than 65 Years and Free of Atherosclerotic Cardiovascular Disease (ASCVD) With Stage 3 or 4 Chronic Kidney Disease (CKD)
Other race includes Asian or Pacific Islander or Hawaiian or American Indian or Alaska Native. AHA indicates American Heart Association; HR, hazard ratio.
Figure 2.
Figure 2.. Association Between Statin Initiation and Major Adverse Cardiovascular Events in US Veterans Older Than 65 Years and Free of Atherosclerotic Cardiovascular Disease (ASCVD), With Stage 3 to 4 Chronic Kidney Disease (CKD)
Other race includes Asian or Pacific Islander or Hawaiian or American Indian or Alaska Native. AHA indicates American Heart Association; HR, hazard ratio.
See this image and copyright information in PMC

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