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Association of Statin Use With All-Cause and Cardiovascular Mortality in US Veterans 75 Years and Older

Educational Objective
To understand the benefits of statin use for individuals 75 years and older.
1 Credit CME
Key Points

Question  Among US veterans 75 years and older and free of atherosclerotic cardiovascular disease at baseline, is statin use associated with lower risk of mortality?

Findings  In this retrospective cohort study that used propensity score overlap weighting and included 326 981 participants, statin use, compared with no statin use, was significantly associated with a lower risk of all-cause and cardiovascular mortality (hazard ratios, 0.75 and 0.80, respectively).

Meaning  Among older US veterans without atherosclerotic cardiovascular disease at baseline, statin therapy was significantly associated with a lower risk of mortality.

Abstract

Importance  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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Article Information

Accepted for Publication: April 25, 2020.

Correction: This article was corrected online on October 13, 2020, for an incorrect data point in the second paragraph and an incorrect column heading in Table 2.

Corresponding Author: Ariela R. Orkaby, MD, MPH, Geriatric Research, Education and Clinical Center (GRECC), VA Boston Healthcare System, 150 S Huntington St, Boston, MA 02130 (aorkaby@bwh.harvard.edu).

Author Contributions: Drs Orkaby and Djousse had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Cho and Djousse contributed equally to this article.

Concept and design: Orkaby, Driver, Ho, Forman, Gaziano, Gagnon, Wilson, Cho.

Acquisition, analysis, or interpretation of data: Orkaby, Driver, Ho, Lu, Costa, Honerlaw, Galloway, Vassy, Gaziano, Gagnon, Wilson, Cho, Djousse.

Drafting of the manuscript: Orkaby, Lu, Honerlaw, Gagnon.

Critical revision of the manuscript for important intellectual content: Orkaby, Driver, Ho, Costa, Galloway, Vassy, Forman, Gaziano, Wilson, Cho, Djousse.

Statistical analysis: Orkaby, Ho, Lu, Vassy, Gagnon, Cho.

Obtained funding: Orkaby, Galloway, Gaziano, Wilson, Cho.

Administrative, technical, or material support: Orkaby, Costa, Honerlaw, Galloway, Vassy, Wilson, Cho.

Supervision: Orkaby, Driver, Gaziano, Wilson, Cho, Djousse.

Conflict of Interest Disclosures: Dr Djousse reported receiving grants from Merck. No other disclosures were reported.

Funding/Support: This research was supported by VA CSR&D CDA-2 award IK2-CX001800 (Dr Orkaby), National Institute on Aging R03-AG060169 (Dr Orkaby), and VA Merit Award I01 CX001025 (Dr Wilson and Dr Cho). This article does not represent the views of the Department of Veterans Affairs or the US government. Support for VA/Centers for Medicare & Medicaid Services data is provided by the Department of Veterans Affairs, VA Health Services Research and Development Service, VA Information Resource Center (project numbers SDR 02-237 and 98-004).

Role of the Funders/Sponsors: The funders/sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank Timothy Treu, MPH (VA Boston Healthcare System), for his technical support. Mr Treu did not receive compensation for his role in the study.

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