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. 2024 Feb 20;3(4):100869.
doi: 10.1016/j.jacadv.2024.100869. eCollection 2024 Apr.

Initiation of Statins for Primary Prevention in Heart Failure With Preserved Ejection Fraction

Ariela R Orkaby  1   2   3 , Parag Goyal  4 , Brian Charest  2 , Saadia Qazi  2   3   5 , Shamlan Sheikh  2   3 , Sanjiv Shah  6 , J Michael Gaziano  2   3 , Luc Djousse  2   3 , David Gagnon  2   7 , Jacob Joseph  2   8   9
Affiliations

Initiation of Statins for Primary Prevention in Heart Failure With Preserved Ejection Fraction

Ariela R Orkaby et al. JACC Adv. .

Abstract

Background: Statins are highly effective for primary prevention of atherosclerotic cardiovascular disease (ASCVD) and mortality. Data on the benefit of statins in adults with heart failure with preserved ejection fraction (HFpEF) and without ASCVD are limited.

Objectives: The purpose of this study was to determine whether statins are associated with a lower risk of mortality and major adverse cardiovascular events (MACE) in HFpEF.

Methods: Veterans Health Administration data from 2002 to 2016, linked to Medicare and Medicaid claims and pharmaceutical data, were collected. Patients had a new HFpEF diagnosis and no known ASCVD or prior statin use at baseline. Cox proportional hazards models were fit to evaluate the association of new statin use with outcomes (all-cause mortality and MACE). Propensity score overlap weighting (PSW) was used to balance baseline characteristics.

Results: Among 7,970 Veterans, 47% initiated a statin over a mean 6.0-year follow-up. At HFpEF diagnosis, mean age was 69 ± 12 years, 96% were male, 67% were White, 14% were Black, and mean EF was 60% ± 6%. Before PSW, statin users were younger with more prevalent metabolic syndrome, arthritis, and other chronic conditions. All characteristics were balanced after PSW. There were 5,314 deaths and 4,859 MACE events. After PSW, the hazard for all-cause mortality for statin users vs nonusers was 22% lower (HR: 0.78; 95% CI: 0.73-0.83). The HR for MACE was 0.79 (95% CI: 0.74-0.84), 0.69 (95% CI: 0.60-0.80) for all-cause hospitalization, and 0.72 (95% CI: 0.59-0.88) for HF hospitalization.

Conclusions: New statin use was associated with reduced all-cause mortality, MACE, and hospitalization in Veterans with HFpEF without prevalent ASCVD.

Keywords: heart failure with preserved ejection fraction; primary prevention; statins.

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Conflict of interest statement

This research was supported by an investigator-initiated grant from Otsuka Pharmaceuticals (Dr Joseph), VA CSR&D CDA-2 award IK2-CX001800 (Dr Orkaby), and 10.13039/100000049National Institute on Aging R03-AG060169 (Dr Orkaby). Drs Djousse and Gaziano have received research funding from 10.13039/100008272Novartis Pharmaceuticals, unrelated to this study. This paper 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). 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. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Association Between Statin Use and All-Cause Mortality in 7,970 U.S. Veterans With HFpEF Free of Atherosclerotic Cardiovascular Disease at Baseline, Stratified by Age, Race, Sex, Frailty, Diabetes, and ASCVD Risk Category Events/N = # of deaths per # of person-years of follow-up; RD = weighted incidence rate difference (ie, the # of fewer deaths per 1,000 Person-years for statin users vs nonusers).
Figure 2
Figure 2
Association Between Statin Use and Major Adverse Cardiovascular Events in 7,970 U.S. Veterans With HFpEF Free of Atherosclerotic Cardiovascular Disease at Baseline, Stratified by Age, Race, Sex, Frailty, Diabetes, and ASCVD Risk Category Events/N = # of deaths per # of person-years of follow-up; RD = weighted incidence rate difference (ie, the # of fewer deaths per 1,000 Person-years for statin users vs nonusers).
Central Illustration
Central Illustration
Association of New Statin Use With All-Cause Mortality, MACE, and Hospitalizations in Veterans HFpEF and No Atherosclerotic Cardiovascular Disease ASCVD = atherosclerotic cardiovascular disease; HF = heart failure; HFpEF = heart failure with preserved ejection fraction; MACE = major adverse cardiovascular events.
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