美国阿拉巴马大学伯明翰分校Katia Bruxvoort团队研究了接种2剂和3剂乙肝疫苗与急性心肌梗死的相关性。2022年3月25日出版的《美国医学会杂志》发表了这项成果。

在许可前试验中，带有胞嘧啶磷鸟嘌呤佐剂的2剂乙肝疫苗（HepB-CpG疫苗；Heplisav-B）比带有氢氧化铝佐剂的3剂乙肝疫苗（HepB-明矾疫苗；Engerix-B）产生了更高的血清保护。然而，在1项试验中，接受HepB-CpG疫苗的患者中观察到急性心肌梗死（MI）事件数高于接受HepB-明矾疫苗的患者，该结果需进一步研究。

为了比较HepB-CpG疫苗和HepB-明矾疫苗接种者MI的发生率，研究组在南加州凯撒永久医疗中心（KPSC）进行了一项前瞻性队列非劣效性研究，KPSC是一个拥有15个医疗中心和大约470万成员的综合医疗保健系统。

该研究包括69625名未接受透析的成年人，他们在2018年8月7日至2019年10月31日（2020年11月30日，最终随访）期间，在KPSC的家庭医学或内科门诊接种了至少1剂乙肝疫苗（HepB-CpG疫苗或HepB-明矾疫苗）。研究期间的第一次剂量为指数剂量。

对接种指数剂量后的患者随访13个月，观察1型MI的发生率。使用诊断代码识别潜在事件，并由心脏病专家判定。通过比较HepB-CpG疫苗接种者和HepB-明矾疫苗接种者，来估计MI的校正危险比（HR），并采用治疗加权逆概率（IPTW）校正人口统计学和临床特征。将单侧97.5%置信区间的上限与非劣效边缘2进行比较。

31183名HepB-CpG疫苗接种者的中位年龄为49岁，51.2%为男性，52.7%为西班牙裔。38442名HepB-明矾疫苗接种者的中位年龄为49岁，50.8%为男性，47.1%为西班牙裔。IPTW后，疫苗组之间的特征非常平衡。

接种HepB-CpG疫苗的受试者中，共确诊了52例1型MI事件，发病率为1.67/1000人-年；在接种HepB-明矾疫苗的受试者中，共确诊71例1型MI事件，确诊率为1.86/1000人-年，校正后的HR为0.92，低于非劣效性边缘。

研究结果表明，在这项队列研究中，与HepB-明矾疫苗相比，接种HepB-CpG疫苗不符合MI风险增加的统计标准。

附：英文原文

Title: Association Between 2-Dose vs 3-Dose Hepatitis B Vaccine and Acute Myocardial Infarction

Author: Katia Bruxvoort, Jeff Slezak, Lei Qian, Lina S. Sy, Bradley Ackerson, Kristi Reynolds, Runxin Huang, Zendi Solano, William Towner, Cheryl Mercado, Steven J. Jacobsen

Issue&Volume: 2022-03-25

Abstract:

Importance  The 2-dose hepatitis B vaccine with a cytosine phosphoguanine adjuvant (HepB-CpG vaccine; Heplisav-B) generated higher seroprotection in prelicensure trials than did a 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant (HepB-alum vaccine; Engerix-B). However, in 1 trial, a higher number of acute myocardial infarction (MI) events were observed among those who received the HepB-CpG vaccine than among those who received the HepB-alum vaccine, an outcome requiring further study.

Objective  To compare the rate of acute MI between recipients of HepB-CpG vaccine and HepB-alum vaccine.

Design, Setting, and Participants  This prospective cohort noninferiority study was conducted at Kaiser Permanente Southern California (KPSC), an integrated health care system with 15 medical centers and approximately 4.7 million members. The study included 69625 adults not undergoing dialysis who received at least 1 dose of a hepatitis B vaccine in either family medicine or internal medicine departments at KPSC from August 7, 2018, to October 31, 2019 (November 30, 2020, final follow-up).

Exposures  Receipt of HepB-CpG vaccine vs HepB-alum vaccine. The first dose during the study period was the index dose.

Main Outcomes and Measures  Individuals were followed up for 13 months after the index dose for occurrence of type 1 acute MI. Potential events were identified using diagnosis codes and adjudicated by cardiologists. The adjusted hazard ratio (HR) of acute MI was estimated comparing recipients of HepB-CpG vaccine with recipients of HepB-alum vaccine, with inverse probability of treatment weighting (IPTW) to adjust for demographic and clinical characteristics. The upper limit of the 1-sided 97.5% CI was compared with a noninferiority margin of 2.

Results  Of the 31183 recipients of HepB-CpG vaccine (median age, 49 years; IQR, 38-56 years), 51.2% (n=15965) were men, and 52.7% (n=16423) were Hispanic. Of the 38442 recipients of HepB-alum (median age, 49 years; IQR, 39-56 years), 50.8% (19533) were men, and 47.1% (n=18125) were Hispanic. Characteristics were well-balanced between vaccine groups after IPTW. Fifty-two type 1 acute MI events were confirmed among recipients of HepB-CpG vaccine for a rate of 1.67 per 1000-person-years, and 71 type 1 acute MI events were confirmed among recipients of HepB-alum vaccine for a rate of 1.86 per 1000 person-years (absolute rate difference, 0.19 [95% CI, 0.82 to 0.44]; adjusted HR, 0.92 [1-sided 97.5% CI, ∞ to 1.32], which was below the noninferiority margin; P<.001 for noninferiority).

Conclusions and Relevance  In this cohort study, receipt of HepB-CpG vaccine compared with HepB-alum vaccine did not meet the statistical criterion for increased risk of acute myocardial infarction.

DOI: 10.1001/jama.2022.2540

Source: https://jamanetwork.com/journals/jama/fullarticle/2790492