The Vital Rhythm Trial: Omega-3 Fatty Acid and Vitamin D Supplementation in the Primary Prevention of Atrial Fibrillation
Author Block: Christine M Albert, Cedars Sinai Medical Ctr, Los Angeles, CA; Nancy R Cook, Julie Pester, Manickavasagar Vinayagamoorthy, Claire Ridge, Brigham and Women's Hosp, Boston, MA; Jacqueline Suk Danik, Brigham and, Boston, MA; Baris Gencer, TIMI Study Group, Boston, MA; Hasan K Siddiqi, Brigham and Women's Hosp, Boston, MA; Chee Ng, Massachusetts General Hosp, Boston, MA; Heike Gibson, Harvrrd Sch of Public Health, Boston, MA; Samia Mora, Julie Elizabeth Buring, JoAnn E Manson, Brigham and Women's Hosp, Boston, MA
Disclosure Block: C.M.Albert: Research Grant; Significant; St. Jude Medical, Abbott, Roche . H.Gibson: None. S.Mora: Speaker/Speaker's Bureau; Modest; Quest Diagnostics. J.E.Buring: None. J.E.Manson: None. N.R.Cook: None. J.Pester: None. M.Vinayagamoorthy: None. C.Ridge: n/a. J.Danik: n/a. B.Gencer: None. H.K.Siddiqi: None. C.Ng: None.
Introduction: Atrial fibrillation (AF) is the most common heart rhythm disturbance and continues to grow in incidence. Once AF develops, a multitude of adverse clinical consequences ensue. Current treatment options employed relatively late in the disease process are associated with limited long-term success and significant risks. Despite the pressing need for primary preventive strategies, AF primary prevention randomized controlled trials (RCTs) have not been performed, largely due to concerns regarding feasibility. Hypothesis: Marine omega-3s and Vitamin D are commonly used supplements which have been implicated in upstream biologic processes leading to the development of AF. Data from observational studies and short-term secondary prevention RCTs have been conflicting, and as a result, both risks and benefits on AF have been postulated. We hypothesized that long-term administration of these supplements might be effective in the primary prevention of AF. Methods: The VITAL Rhythm Study (HL116690; NCT02178410) is an AF primary prevention RCT embedded within the VITamin D and OmegA-3 TriaL (VITAL trial; NCT01169259) that tested supplementation with vitamin D3 (2000 IU/day) and omega-3 fatty acids (EPA:DHA in 1:3 ratio, 840mg/day) in a 2x2 factorial design for the prevention of CVD and cancer among 25,871 men (aged 50+ years) and women (aged 55+ years). Incident AF diagnoses were prospectively ascertained both by participant self-report and linkage to claims data from Centers for Medicare and Medicaid Services (CMS). An event committee reviewed medical records pertaining to AF diagnoses, and ECG evidence of AF and/or a physician’s report documenting a new diagnosis of AF were required for confirmation of the primary endpoint. The separate main effects of intention-to-treat with EPA/DHA and Vitamin D3 on AF incidence will be estimated using Cox proportional hazards models and event-free survival curves using Kaplan-Meier estimates and the log-rank test. Results: From the parent VITAL trial, 25119 participants without a history of AF were enrolled in the VITAL Rhythm Study (mean age 67, 51% women, 21% black) and were followed for a median of 5.3 years at the end of randomized treatment, December 31, 2017. The last reported AF diagnoses occurring during the trial were ascertained by CMS linkage in October 2019. Currently, 888 incident AF events have been confirmed as occurring during randomized treatment, and AF adjudication will be completed by September 2020. Final analyses will be presented for both arms for the primary endpoint of incident AF as well as for AF subtypes of paroxysmal and non-paroxysmal AF. We are currently > 90% powered to detect to detect a 20% reduction or increase in AF incidence. Conclusions: The results from this first-of-its-kind AF primary prevention RCT will provide much needed data on the long-term benefits and risks of these commonly used supplements on AF incidence.