高剂量与标准剂量四价流感疫苗在老年心血管疾病患者中的相对有效性：DANFLU-1随机临床试验的预先设定分析。

Relative Effectiveness of High-Dose Versus Standard-Dose Quadrivalent Influenza Vaccine in Older Adults With Cardiovascular Disease: A Prespecified Analysis of the DANFLU-1 Randomized Clinical Trial.

作者信息

Christensen Jacob, Johansen Niklas Dyrby, Modin Daniel, Janstrup Kira Hyldekær, Nealon Joshua, Samson Sandrine, Loiacono Matthew, Harris Rebecca, Larsen Carsten Schade, Jensen Anne Marie Reimer, Landler Nino Emanuel, Claggett Brian L, Solomon Scott D, Gislason Gunnar H, Køber Lars, Landray Martin J, Sivapalan Pradeesh, Jensen Jens Ulrik Stæhr, Biering-Sørensen Tor

机构信息

Center for Translational Cardiology and Pragmatic Randomized Trials (J.C., N.D.J., D.M., K.H.J., A.M.R.J., N.E.L., T.B.-S.), Copenhagen University Hospital, Herlev and Gentofte, Denmark.

Cardiovascular Non-Invasive Imaging Research Laboratory, Department of Cardiology (J.C., N.D.J., D.M., K.H.J., A.M.R.J., N.E.L., T.B.-S.), Copenhagen University Hospital, Herlev and Gentofte, Denmark.

出版信息

Circ Cardiovasc Qual Outcomes. 2025 Feb;18(2):e011496. doi: 10.1161/CIRCOUTCOMES.124.011496. Epub 2024 Aug 31.

DOI:10.1161/CIRCOUTCOMES.124.011496

PMID:39215646

Abstract

BACKGROUND

Influenza vaccination reduces the risk of adverse outcomes in patients with cardiovascular disease (CVD). We sought to evaluate whether the presence of CVD modified the relative effectiveness of the high-dose quadrivalent influenza vaccine (QIV-HD) versus standard-dose quadrivalent influenza vaccine (QIV-SD) in this prespecified analysis of the DANFLU-1 trial (Feasibility of Randomizing Danish Citizens Aged 65-79 Years to High-Dose Quadrivalent Influenza Vaccine Versus Standard-Dose Quadrivalent Influenza Vaccine in a Pragmatic Registry-Based Setting).

METHODS

DANFLU-1 was a pragmatic, open-label, randomized feasibility trial of QIV-HD versus QIV-SD in adults aged 65 to 79 years during the 2021/2022 influenza season in Denmark. Vaccines were allocated in a 1:1 ratio. Baseline and follow-up data regarding diagnoses and mortality were obtained from Danish national registers. The trial is registered at Clinicaltrials.gov: NCT05048589. The CVDs assessed included heart failure, ischemic heart disease, atrial fibrillation, and a combined group denoted chronic CVD consisting of the aforementioned diseases, among others. Prespecified outcomes included hospitalizations for pneumonia or influenza, respiratory disease, CVD, cardiorespiratory disease, all-cause hospitalizations, and mortality. Effect modification was tested using interaction terms.

RESULTS

The final study population included 12 477 participants (mean age of 71.7±3.9 years and 5877 [47.1%] were female), of whom 2540 (20.4%) had chronic CVD. QIV-HD versus QIV-SD was associated with a lower incidence of hospitalizations for pneumonia or influenza (incidence rate ratio [IRR], 0.30 [95% CI, 0.14-0.64]) and all-cause mortality (IRR, 0.51 [95% CI, 0.30-0.86]) regardless of chronic CVD (=0.57 and 0.49, respectively). The relative effectiveness of QIV-HD versus QIV-SD against all-cause hospitalizations was modified in participants with chronic CVD (overall: IRR, 0.87 [95% CI, 0.76-0.99]; no chronic CVD: IRR, 0.79 [95% CI, 0.67-0.92]; chronic CVD: IRR, 1.11 [95% CI, 0.88-1.39]; =0.026). No other effect modification was observed by the presence of chronic CVD, heart failure, ischemic heart disease, or atrial fibrillation.

CONCLUSIONS

The relative effectiveness of QIV-HD versus QIV-SD was consistent against hospitalizations for pneumonia or influenza and all-cause mortality regardless of chronic CVD. However, the relative effectiveness against all-cause hospitalizations was modified by the presence of chronic CVD. These results should be considered hypothesis generating.

REGISTRATION

URL: https://www.clinicaltrials.gov; Unique identifier: NCT05048589.

摘要

背景

流感疫苗接种可降低心血管疾病（CVD）患者出现不良后果的风险。在这项对DANFLU-1试验（在基于实用登记的环境中将65至79岁丹麦公民随机分配至高剂量四价流感疫苗与标准剂量四价流感疫苗的可行性）的预先设定分析中，我们试图评估CVD的存在是否改变了高剂量四价流感疫苗（QIV-HD）与标准剂量四价流感疫苗（QIV-SD）的相对有效性。

方法

DANFLU-1是一项在丹麦2021/2022流感季节对65至79岁成年人进行的QIV-HD与QIV-SD的实用、开放标签、随机可行性试验。疫苗按1:1比例分配。关于诊断和死亡率的基线及随访数据来自丹麦国家登记处。该试验已在Clinicaltrials.gov注册：NCT05048589。评估的心血管疾病包括心力衰竭、缺血性心脏病、心房颤动，以及一个由上述疾病等组成的称为慢性心血管疾病的组合组。预先设定的结局包括因肺炎或流感、呼吸系统疾病、心血管疾病、心肺疾病导致的住院、全因住院和死亡率。使用交互项检验效应修饰。

结果

最终研究人群包括12477名参与者（平均年龄71.7±3.9岁，5877名[47.1%]为女性），其中2540名（20.4%）患有慢性心血管疾病。无论是否患有慢性心血管疾病（分别为=0.57和0.49），QIV-HD与QIV-SD相比，因肺炎或流感导致的住院发生率（发生率比值[IRR]，0.30[95%CI，0.14 - 0.64]）和全因死亡率（IRR，0.51[95%CI，0.30 - 0.86]）较低。在患有慢性心血管疾病的参与者中，QIV-HD与QIV-SD相比在预防全因住院方面的相对有效性有所改变（总体：IRR，0.87[95%CI，0.76 - 0.99]；无慢性心血管疾病：IRR，0.79[95%CI，0.67 - 0.92]；慢性心血管疾病：IRR，1.11[95%CI，0.88 - 1.39]；=0.026）。未观察到慢性心血管疾病、心力衰竭、缺血性心脏病或心房颤动的存在对其他方面的效应修饰。