The VITAL Rhythm Study

心房颤动（AF）仍然是最常见的心律失常， 呈指数增长目前估计全世界有3350万人患有AF。 房颤已确定，与显着的发病率和死亡率相关，其中大部分不受当前的影响 治疗方案。在这项竞争性的VITAL节律研究的延续中，我们建议继续我们的 海洋欧米茄-3脂肪酸（840毫克二十碳五烯酸）的益处和风险平衡评估 [EPA]+二十二碳六烯酸[DHA]）和维生素D3（2，000 IU/天胆钙化醇）对AF发病率的影响 NIH资助的大规模临床试验，维生素D和OmegA-3 TriaL（VITAL）。Vital是一个 正在进行的随机、双盲、安慰剂对照、2x2析因试验，专门设计用于评估 维生素D3和海洋ω-3脂肪酸补充剂在癌症初级预防中的功效， 25，874名男性（50岁以上）和女性（55岁以上）的心血管疾病。获益和风险 关于AF事件，这两种常用补充剂的假设是基于 结果来自观察性研究和短期二级预防随机试验，但数据明确 缺乏大规模的一级预防随机试验。在这个竞争的延续中，我们建议 继续我们的辅助研究，该研究正在确定和裁定AF结局， VITAL试验，以测试是否长期治疗（5年）与ω-3脂肪酸和/或维生素D3 补充剂对老年人群7年随访期间的AF发生率有影响。情况 正在对房颤事件进行验证，包括系统确定医生对房颤的诊断， 每年的研究问卷，补充CMS链接，然后收集详细的诊断 医疗记录的信息。延长的随访将使我们能够充分确定和裁定房颤 在整个5年VITAL随机试验和2年干预后阶段发生的终点，以及 确定这些药物是否可能对持续性房颤和阵发性房颤产生选择性影响。 由于已知这两种药物都会影响心房结构和电生理过程中的生物学过程， 重塑、长期干预后获益和/或对持续性房颤的选择性获益， 貌似有理继续沿着单独判定的其他终点 在VITAL试验中对血浆25（OH）D和EPA+DHA测定的资助测量也将使我们能够 根据性别和基线营养水平进行重要的子分析。总之，我们建议建立 在第一个供资周期建立的基础设施和流程，并继续利用 在VITAL试验中投入了大量资源和基础设施，以提供一个明确和全面的 评估这些药物对AF发生率和持续性的获益和风险。如果是有益的， 药物将代表首个被证明有效预防房颤的疗法。

Atrial fibrillation (AF) remains the most common heart rhythm disturbance and the prevalence continues to grow exponentially. It is currently estimated that 33.5 million people worldwide are afflicted with AF. Once established, AF is associated with significant morbidity and mortality, much of which is not impacted by current treatment options. In this competing continuation of the VITAL Rhythm Study, we propose to continue our evaluation of the balance of benefits and risks of marine omega-3 fatty acid (840 mg eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) and vitamin D3 (2,000 IU/day cholecalciferol) on AF incidence in the setting of an NIH-funded large-scale clinical trial, the VITamin D and OmegA-3 TriaL (VITAL). VITAL is an ongoing, randomized, double-blind, placebo-controlled, 2x2 factorial trial specifically designed to evaluate the efficacy of vitamin D3 and marine omega-3 fatty acid supplements in the primary prevention of cancer and cardiovascular disease among 25,874 men (aged 50+ years) and women (aged 55+ years). Benefits and risks with respect to incident AF have been postulated for both of these commonly used supplements based on results from observational studies and short-term secondary prevention randomized trials, but definitive data from a large-scale primary prevention randomized trial are lacking. In this competing continuation, we propose to continue our ancillary study that is in the process of ascertaining and adjudicating AF outcomes within the VITAL trial to test whether long-term treatment (5-years) with omega-3 fatty acid and/or vitamin D3 supplementation has an impact on the incidence AF over 7-years of follow-up in an older population. Case validation of incident AF is ongoing and involves systematic ascertainment of physician diagnoses of AF on annual study questionnaires supplemented by CMS linkage followed by collection of detailed diagnostic information from medical records. The extended follow-up will allow us to fully ascertain and adjudicate the AF endpoints occurring throughout the 5 year VITAL randomized trial and a 2-year post-intervention period and determine whether these agents might have a selective impact on persistent versus paroxysmal forms of AF. Since both agents are known to impact biologic processes involved in atrial structural and electrical remodeling, long-term post-intervention benefits and/or selective benefits on persistent forms of AF are plausible. The additional endpoints that will be adjudicated during the continuation along with the separately funded measurements of plasma 25(OH)D and EPA+DHA assays in the VITAL trial will also allow us to perform important sub-analyses according to sex and baseline nutrient level. In summary, we propose to build on the infrastructure and processes created in the first funding cycle and continue to take advantage of the enormous investment of resources and infrastructure in the VITAL trial to provide a definitive and full assessment of the benefits and risks of these agents on AF incidence and persistence. If beneficial, then these agents would represent the first therapy proven effective for AF prevention.