ImportanceHigh-dose trivalent compared with standard-dose quadrivalent influenza vaccine did not significantly reduce all-cause mortality or cardiopulmonary hospitalizations in patients with high-risk cardiovascular disease in the INVESTED trial. Whether humoral immune response to influenza vaccine is associated with clinical outcomes is unknown.ObjectiveTo examine the antibody response to high-dose trivalent compared with standard-dose quadrivalent inactivated influenza vaccine and its associations with clinical outcomes.Design, Setting, and ParticipantsThis secondary analysis is a prespecified analysis of the immune response substudy of the randomized, double-blind, active-controlled INVESTED trial, which was conducted at 157 sites in the United States and Canada over 3 influenza seasons between September 2016 and January 2019. Antibody titers were determined by hemagglutination inhibition assays at randomization and 4 weeks during the 2017-2018 and 2018-2019 seasons. Eligibility criteria included recent acute myocardial infarction or heart failure hospitalization and at least 1 additional risk factor. Data were analyzed from February 2023 to June 2023.Main Outcomes and MeasuresMean antibody titer change, seroprotection (antibody titer level ≥1:40) and seroconversion (≥4-fold increase in titer) at 4 weeks, and the association between seroconversion status and the risk for adverse clinical outcomes.InterventionsHigh-dose trivalent or standard-dose quadrivalent inactivated influenza vaccine, with revaccination up to 3 seasons.ResultsAntibody data were available for 658 of 5260 randomized participants (12.5%; mean [SD] age, 66.2 [11.4] years; 507 male [77.1%], 151 female [22.9%]; 348 with heart failure [52.9%]). High-dose vaccine was associated with an increased magnitude in antibody titers for A/H1N1, A/H3N2, and B-type antigens compared with standard dose. More than 92% of all participants achieved seroprotection for each of the contained antigens, while seroconversion rates were higher in participants who received high-dose vaccine. Seroconversion for any antigen was not associated with the risk for cardiopulmonary hospitalizations or all-cause mortality (hazard ratio, 1.09; 95% CI, 0.79-1.53; P = .59), irrespective of randomized treatment (P = .38 for interaction).Conclusions and RelevanceHigh-dose vaccine elicited a more robust humoral response in patients with heart failure or prior myocardial infarction enrolled in the INVESTED trial, with no association between seroconversion status and the risk for cardiopulmonary hospitalizations or all-cause mortality. Vaccination to prevent influenza remains critical in high-risk populations.Trial RegistrationClinicalTrials.gov Identifier: NCT02787044

中文翻译：

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高危心血管疾病患者的流感疫苗免疫反应

重要性 在 INVESTED 试验中，与标准剂量四价流感疫苗相比，高剂量三价流感疫苗并未显着降低高危心血管疾病患者的全因死亡率或心肺住院率。对流感疫苗的体液免疫反应是否与临床结果相关尚不清楚。目的检查与标准剂量四价灭活流感疫苗相比，高剂量三价灭活流感疫苗的抗体反应及其与临床结果的关联。设计、设置和参与者此二次分析是对随机、双盲、主动对照 INVESTED 试验的免疫反应亚研究进行预先指定的分析，该试验在 2016 年 9 月至 2019 年 1 月的 3 个流感季节在美国和加拿大的 157 个地点进行。 2017-2018 赛季和 2018-2019 赛季随机和 4 周进行血凝抑制测定。资格标准包括近期急性心肌梗死或心力衰竭住院治疗以及至少 1 个其他危险因素。数据分析时间为 2023 年 2 月至 2023 年 6 月。 主要结果和测量 4 周时的平均抗体滴度变化、血清保护（抗体滴度水平≥1:40）和血清转化（滴度增加≥4 倍），以及血清转化状态与血清转化之间的关联。干预措施高剂量三价或标准剂量四价灭活流感疫苗，重新接种最多 3 个季节。结果 5260 名随机参与者中的 658 名获得了抗体数据（12.5%；平均 [SD] 年龄，66.2 [11.4] ] 年；507 名男性 [77.1%]，151 名女性 [22.9%]；348 名患有心力衰竭 [52.9%]）。与标准剂量相比，高剂量疫苗与 A/H1N1、A/H3N2 和 B 型抗原的抗体滴度增加有关。超过 92% 的参与者对每种所含抗原都实现了血清保护，而接受高剂量疫苗的参与者的血清转化率更高。任何抗原的血清转化与心肺住院或全因死亡的风险无关（风险比，1.09；95% CI，0.79-1.53​​；磷= .59），无论随机治疗（磷= .38（交互作用））。结论和相关性高剂量疫苗在参与 INVESTED 试验的心力衰竭或既往心肌梗死患者中引发了更强烈的体液反应，血清转化状态与心肺住院或全因住院风险之间没有关联死亡。预防流感的疫苗接种对于高危人群仍然至关重要。试验注册ClinicalTrials.gov 标识符：NCT02787044