The VITAL Rhythm Study

房颤(房颤)仍然是最常见的心律失常，而且患病率仍在继续。 成倍增长。据估计，目前全球有3350万人患有房颤。一次 房颤的确诊与严重的发病率和死亡率有关，其中大部分不受当前疾病的影响 治疗方案。在这项重要节律研究的竞争性延续中，我们建议继续我们的 海洋omega-3脂肪酸(840毫克二十碳五烯酸)的利弊平衡评价 [EPA]+二十二碳六烯酸[DHA])和维生素D3(2,000IU/天胆钙化醇)对房颤发病率的影响 由美国国立卫生研究院资助的大规模临床试验，即维生素D和omega-3试验(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omega-3脂肪酸补充剂在一级预防癌症和 25,874名男性(50岁以上)和女性(55岁以上)患有心血管疾病。收益与风险 关于事件房颤，这两种常用的补充剂都是基于以下假设的 来自观察性研究和短期二级预防随机试验的结果，但确定的数据 从大规模的初级预防来看，缺乏随机试验。在这一竞争的延续中，我们建议 继续我们的辅助研究，即在确定和判断房颤结果的过程中 一项重要试验，以测试欧米茄-3脂肪酸和/或维生素D3的长期治疗(5年)是否 补充剂对老年人群7年以上随访的房颤发生率有影响。案例 房颤事件的确认正在进行中，包括系统地确定医生对房颤的诊断 由CMS连锁补充的年度研究问卷，然后收集详细的诊断 医疗记录中的信息。延长的后续行动将使我们能够充分确定和裁决房颤 在5年的VITAL随机试验和2年的干预后期间发生的终点 确定这些药物是否对持续性房颤和阵发性房颤有选择性影响。 由于已知这两种药物都会影响涉及心房结构和电信号的生物过程 持续性房颤的重塑、长期介入后益处和/或选择性益处包括 看似合理。将在继续期间与单独的 在VITAL试验中对血浆25(OH)D和EPA+DHA分析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。总而言之，我们建议建立 关于在第一个供资周期中建立的基础设施和进程，并继续利用 在至关重要的试验中投入巨大的资源和基础设施，以提供最终和完整的 评估这些药物对房颤发生率和持续性的益处和风险。如果有益，那么这些 药物将是第一种被证明有效预防房颤的治疗方法。

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.