A randomized controlled trial of influenza vaccine to prevent adverse vascular events.

心血管疾病是全球死亡的主要原因，估计每年造成约1700万人死亡。心脏病和中风占所有死亡人数的近三分之一，是住院治疗的主要原因。充血性心力衰竭（CHF）患者的风险特别高。临床试验表明，近三分之一的CHF患者会发生心肌梗死（MI）、卒中或因CHF住院治疗。观察性研究已经确定了流感感染与主要不良血管事件之间的关联。因此，对CHF患者这样的高危人群接种流感疫苗可能会预防不良血管事件。然而，这些研究存在偏倚，需要设计良好的临床试验来测试流感疫苗接种对预防不良血管事件的影响。本研究的目的是评估灭活流感疫苗是否可以减少高风险参与者的不良血管事件。我们将在三个流感季节内，将血管不良事件高危患者随机分配至每年接种一次灭活流感疫苗或安慰剂组。主要结局是心血管（CV）死亡、非致死性心肌梗死（MI）、非致死性卒中和因CHF住院的复合终点。我们将从七个国家的中心招募3，500名参与者：菲律宾（牵头中心）、莫桑比克、苏丹、乌干达、沙特阿拉伯、马来西亚和中国。这项随机试验对主要不良血管事件高危患者的管理具有重要意义。尽管许多国家每年都建议糖尿病和心血管疾病患者接种流感疫苗，但这些建议的接受率相对较低。大多数辖区的心脏病专家通常不建议他们的患者每年接种流感疫苗，作为减少未来不良血管事件（如急性冠状动脉综合征或中风）的策略。心脏病患者的流感疫苗接种率因国家而异，但在INTER-CHF研究中心（将进行试验），平均为11%。严格证明流感疫苗导致主要不良血管事件减少将是一项具有里程碑意义的研究。我们预计，这样的试验将影响医生对主要血管事件高风险患者的管理决策。我们建议测试的效果大小与现有的二级预防策略相当，并且考虑到疫苗每年接种一次的事实，它既简单又便宜。考虑到巨大的疾病负担，降低心血管和卒中相关死亡的可能性是本试验的一个令人信服的论据。如果流感疫苗被证明可以减少不良血管事件，这将代表如何预防不良血管事件的重要变化。事实上，我们的主要结果是一个复合，包括各种形式的血管疾病将增加普遍性。这项研究将是一个里程碑，有助于以证据为基础的临床以及公共卫生政策。

Cardiovascular disease is a leading cause of death globally estimated to be responsible for approximately 17 million deaths annually. Heart disease and stroke account for nearly one third of all deaths and are a major cause of hospitalization. Patients with congestive heart failure (CHF) are at particularly high risk. Clinical trials demonstrate that nearly one third of patients with CHF will experience a myocardial infarction (MI), stroke, or hospitalization for CHF. Observational studies have established an association between influenza infection and major adverse vascular events . It follows that vaccinating such a high risk group as patients with CHF against influenza may prevent adverse vascular events. However, these studies are subject to bias and a well designed clinical trial is needed to test the effect of influenza vaccination on preventing adverse vascular events. The goal of this study is to assess whether inactivated influenza vaccine can reduce adverse vascular events in high risk participants. We will address the question by randomizing patients at high risk for adverse vascular events to either annual inactivated influenza vaccine or to placebo over three influenza seasons. The primary outcome is a composite of cardiovascular (CV) death, non-fatal myocardial infarction (MI), non- fatal stroke, and hospitalization for CHF. We will enroll 3,500 participants from centres in seven countries: Philippines (the lead centre), Mozambique, Sudan, Uganda, Saudi Arabia, Malaysia, China. This proposed randomized trial has important implications for the management of patients at high risk for major adverse vascular events. Although the influenza vaccine is recommended annually for groups with diabetes and cardiovascular disease in many counties, uptake of these recommendations is relatively low. Cardiologists in most jurisdictions do not routinely recommend annual influenza vaccine for their patients as a strategy to reduce future adverse vascular events such as acute coronary syndrome or stroke. Uptake of influenza vaccine in patients with heart disease varies by country but in INTER-CHF sites (where are trial will be conducted) is 11% on average. Rigorous demonstration of influenza vaccine leading to a reduction in major adverse vascular events would represent a landmark study. We anticipate that such a trial would influence management decisions by physicians for patients at high risk for major vascular events. The effect size we propose testing is comparable to secondary prevention strategies available and given the fact that a vaccine is given once annually it is simple and inexpensive. Given the large burden of disease, the possibility to reduce cardiovascular and stroke related death is a compelling argument for this trial. If influenza vaccine is shown to reduce adverse vascular events, it will represent an important change in how prevention of adverse vascular events is thought about. The fact that our primary outcome is a composite, including various forms of vascular disease will increase generalizability. The study would be a milestone in contributing to evidence-based clinical as well public health policy.