Statin Use and All-Cause and Cardiovascular Mortality in US Veterans ≥75 Years
abstract
This abstract is available on the publisher's site.
Access this abstract nowImportance
Data are limited regarding statin therapy for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in adults 75 years and older.
Objective
To evaluate the role of statin use for mortality and primary prevention of ASCVD in veterans 75 years and older.
Design, Setting, and Participants
Retrospective cohort study that used Veterans Health Administration (VHA) data on adults 75 years and older, free of ASCVD, and with a clinical visit in 2002-2012. Follow-up continued through December 31, 2016. All data were linked to Medicare and Medicaid claims and pharmaceutical data. A new-user design was used, excluding those with any prior statin use. Cox proportional hazards models were fit to evaluate the association of statin use with outcomes. Analyses were conducted using propensity score overlap weighting to balance baseline characteristics.
Exposures
Any new statin prescription.
Main Outcomes and Measures
The primary outcomes were all-cause and cardiovascular mortality. Secondary outcomes included a composite of ASCVD events (myocardial infarction, ischemic stroke, and revascularization with coronary artery bypass graft surgery or percutaneous coronary intervention).
Results
Of 326 981 eligible veterans (mean [SD] age, 81.1 [4.1] years; 97% men; 91% white), 57 178 (17.5%) newly initiated statins during the study period. During a mean follow-up of 6.8 (SD, 3.9) years, a total 206 902 deaths occurred including 53 296 cardiovascular deaths, with 78.7 and 98.2 total deaths/1000 person-years among statin users and nonusers, respectively (weighted incidence rate difference [IRD]/1000 person-years, -19.5 [95% CI, -20.4 to -18.5]). There were 22.6 and 25.7 cardiovascular deaths per 1000 person-years among statin users and nonusers, respectively (weighted IRD/1000 person-years, -3.1 [95 CI, -3.6 to -2.6]). For the composite ASCVD outcome there were 123 379 events, with 66.3 and 70.4 events/1000 person-years among statin users and nonusers, respectively (weighted IRD/1000 person-years, -4.1 [95% CI, -5.1 to -3.0]). After propensity score overlap weighting was applied, the hazard ratio was 0.75 (95% CI, 0.74-0.76) for all-cause mortality, 0.80 (95% CI, 0.78-0.81) for cardiovascular mortality, and 0.92 (95% CI, 0.91-0.94) for a composite of ASCVD events when comparing statin users with nonusers.
Conclusions and Relevance
Among US veterans 75 years and older and free of ASCVD at baseline, new statin use was significantly associated with a lower risk of all-cause and cardiovascular mortality. Further research, including from randomized clinical trials, is needed to more definitively determine the role of statin therapy in older adults for primary prevention of ASCVD.
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Additional Info
Disclosure statements are available on the authors' profiles:
Association of Statin Use With All-Cause and Cardiovascular Mortality in US Veterans 75 Years and Older
JAMA 2020 Jul 07;324(1)68-78, AR Orkaby, JA Driver, YL Ho, B Lu, L Costa, J Honerlaw, A Galloway, JL Vassy, DE Forman, JM Gaziano, DR Gagnon, PWF Wilson, K Cho, L DjousseFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Should we Start Statin Therapy in Someone Over the Age of 75 Years?
The instinctive response is that starting a statin at that age does not make sense because you need time to reap the benefits and it is too late for them. Also, there are very few studies in this age category so there is no evidence that it will work. Even the authors of this study point out that, in the statin trials which included over 160,000 patients, fewer than 2% of the participants were over the age of 75 years. In fact, in the current climate, many are advocating deprescribing in this age bracket as opposed to starting new therapies.
However, the elderly population is growing at an extremely fast rate as the baby boomers continue to enter this age bracket. Can we protect them from having a heart attack or stroke or dying prematurely with statin therapy? It is unlikely that we will be able to do a randomized placebo-controlled trial in this population. The next best thing is to look at real-world data to see if there are benefits of starting a statin in patients over the age of 75 years.
This research group searched the US Veterans Health Administration services database and they found 326,981 veterans who over the age of 75 years who did not have ASCVD at baseline (primary prevention) and had a complete medical record. Of these 326,981 veterans, 57,178 (17.5%) were new statin users and the rest never had a statin prescription.
The mean age was 81.1 (range, 75–107) years, with 91.0% being white and 97.3% being men. The most common statin was simvastatin at 84.8% then lovastatin at 11.0%, and the more modern statins, atorvastatin and rosuvastatin, were only used in 0.5% of the statin users.
The mean follow-up for this study was 6.8 years (SD, 3.9) and there were 206,902 deaths, of which 53,296 were cardiovascular deaths. After propensity score matching, the statin use was associated with 25% less all-cause mortality (HR, 0.75; 95% CI, 0.74–0.76; P < .001) and 20% less cardiovascular death (HR, 0.80; 95% CI, 0.78–0.81; P < .001).
Also, there were 123,379 ASCVD events, which included myocardial infarction, ischemic stroke, or CABG/PCI. Statin use was associated with an 8% reduction in ASCVD events (HR, 0.92; 95% CI, 0.91–0.94; P < .001). CABG/PCI on its own was significantly reduced by 11% (HR, 0.89; 95% CI, 0.88–0.91; P < .001).
In the subgroup analysis evaluating death outcomes, there was benefit regardless of age. Even patients older than 90 years at baseline experienced benefit. Even in patients who had dementia, there was a death benefit.
These data are not as strong as would be from a true randomized trial, but, in all honesty, it is very unlikely that there will ever be a randomized, placebo-controlled trial of statin use in patients over the age of 75 years. This study provides the best data that we can get, and it is quite clear that starting a statin, even in the older age, has benefits in hard outcomes such as death and ASCVD events. There are very few things that we do that can reduce death in the elderly population, so no more debating. Let’s just protect the elderly from dying and from ASCVD—just do it.