Statin Initiation, Mortality in Older Individuals With Moderate CKD

The leading cause of death among older adults with chronic kidney disease (CKD) is atherosclerotic cardiovascular disease (ASCVD). There are few data available on the role of statins for the prevention of primary ASCVD in patients with moderate CKD (stages 3-4). Results of a meta-analysis of 8834 participants in primary prevention trials with CKD, primarily stage 3, demonstrated a 41% reduction in ASCVD events and a 34% reduction in total mortality. Conversely, there is evidence that there is no benefit to initiating statins in those receiving hemodialysis. 

According to Odeya Barayev, MD, MBA, and colleagues, the trials supporting use of statins for primary prevention of ASCVD in patients with moderate CKD included only a few older adults. Using data from the Veterans Health Administration (VA), Dr. Barayev et al conducted a study to assess the association of statin initiation with mortality and major adverse cardiovascular events (MACE) among older adults following a diagnosis of moderate CKD (stages 3-4). Results of the study were reported in JAMA Network Open. 

Using nested trials with a propensity weighting approach, the cohort study employed a target trial emulation for statin initiation among veterans with moderate CKD. Linked data from the VA Healthcare System, Medicare, and Medicaid were used. The study population included US veterans newly diagnosed with moderate CKD between 2005 and 2015 in the VA, with follow-up through December 31, 2017. Eligible veterans were older than 65 years, within 5 years of CKD diagnosis, had no prior ASCVD or statin use, and had at least one clinical visit in the year prior to trial baseline 

For each nested trial, researchers assessed eligibility criteria and ran Cox proportional hazards models with bootstrapping. Data analysis was conducted from July 2021 to October 2023. The primary outcome of interest was all-cause mortality. Time to first MACE (myocardial infarction, transient ischemic attack, stroke, revascularization, or mortality) was also assessed. 

The study analysis included 14,828 individual veterans contributing to 154,167 nested person-trials. Mean age at the time of CKD diagnosis was 76.9 years, 99% (n=14,616) were men, 72% (n=10,539) were White, and 17% (n=2568) were Black. 

After expanding to person-trials and assessing eligibility at baseline, the analyses included 151,243 person-trials (14,685 individuals) of nonstatin initiators and 2924 person-trials (2924 individuals) of statin initiators. Compared with the nonstatin initiators, the veterans in the statin initiator group were younger, had higher body mass index, and were more likely to have diagnostic codes for diabetes, hypertension, and hyperlipidemia. They were also more likely to have polypharmacy, take antihypertensives, be frail, and have CKD stage 4 (vs 3) at baseline. 

In the statin initiator group, statin initiation, or trial baseline date, tended to occur closer to the date of the diagnosis of moderate CKD, approximately 17 months following diagnosis, compared with the mean of approximately 22 months after diagnosis among the noninitiator person-trials. Following propensity score overlap weighting, all baseline characteristics were balanced. The most common prescribed statin was simvastatin (46%; n=1357), followed by atorvastatin (33%; n=973), pravastatin (15%; n=434), and lovastatin (3%; n=80). 

During a mean follow-up of 3.6 years, there were 744 deaths among the statin initiator person-trials and 47,743 deaths in the noninitiator person-trials. The estimated hazard ratio (HR) for all-cause mortality was 0.91 (95% CI, 0.85-0.97), indicating a 9% lower risk of death for those who initiated statins within the first 5 years after a diagnosis of moderate CKD. 

In analyses of subgroups by sex, age, race, risk of ASCVD, frailty, diabetes, hyperlipidemia, and CKD stage, there was a similar protective pattern for statin therapy initiators compared with noninitiators (for example, age, 64-74 years: HR, 0.85; 95% CI, 0.76-0.96 and age, ≥75 years: HR, 0.89; 95% CI, 0.82-0.97). 

For the secondary outcome of time to first MACE, there were a total of 57,772 MACE: 988 among statin initiator person-trials and 56,734 among nonstatin initiator person-trials. Following propensity score overlap weighting, there was a 4% lower risk of MACE with statin initiation (HR, 0.96; 95% CI, 0.91-1.02). However, the results did not reach statistical significance. Results were unchanged in analysis by subgroups (for example, age, 64-74 years: HR, 0.95; 95% CI, 0.86-1.06 and age, ≥75 years: HR, 0.93; 95% CI, 0.86-1.01). 

The researchers cited some limitations to the study, including the study population being predominantly male and White, potentially limiting the generalizability of the findings to other populations; the possibility of residual unmeasured confounding due to the nature of administrative data; not evaluating the per-protocol effect size for statin use after the initial prescription; and not evaluating the dose or duration of statin therapy during the follow-up period. 

In conclusion, the authors said, “Among US veterans older than 65 years with CKD stages 3 to 4 and no prior ASCVD, statin initiation was associated with a lower risk of all-cause mortality compared with no statin initiation. Results should be confirmed in a randomized, clinical trial. However, until such trials are completed, these data argue against withholding or deprescribing statins for primary prevention in older patients with CKD stages 3 to 4.” 

Source: JAMA Network Open