Two-Dose Hepatitis B Vaccine No More Likely to Result in Cardiac Event

Until a few years ago, adults looking to be inoculated against hepatitis B were given a 3-dose vaccine such as a HepB-alum vaccine, which has an aluminum hydroxide adjuvant. In 2017, the Food and Drug Administration (FDA) approved a 2-dose vaccine containing a cytosine phosphoguanine adjuvant (HepB-CpG). Clinical trials showed that the 2-dose HepB-CpG offered significantly higher and earlier protection than the 3-dose vaccine, with a similar safety profile characterized by mild and infrequent adverse events.

One clinical trial, however, resulted in 14 participants (0.25%) who received the HepB-CpG vaccine experiencing an acute myocardial infarction (MI), compared with 1 participant (0.04%) who received the HepB-alum vaccine experiencing the same. The FDA requested a postmarketing study of acute MI risk, spurring a large prospective cohort study carried out using data from patients seen at 15 different Kaiser Permanente Southern California medical centers.

The study, conducted by scientists at the University of Alabama Birmingham and Kaiser Permanente in Southern California and published in JAMA, included 31,183 patients who received the 2-dose HepB-CpG vaccine series and 38,442 who got the 3-dose HepB-alum vaccine series between August 2018 and October 2019. The incidence of previous comorbidities, number of risk factors for cardiovascular disease, number of cardiovascular medications taken, and level of health care usage were roughly even between the cohorts.

During the study, 74 potential acute MI events occurred among participants taking the HepB-CpG vaccine and 128 potential acute MI events happened in the group taking the HepB-alum vaccine. Out of those, 52 in the HepB-CpG group were determined to be acute MIs, while 71 in the HepB-alum group were acute MIs. Expressed in person-years, the acute MI rate was 1.67 per 1000 person-years in the HepB-CpG group, compared with 1.86 per 1,000 person-years in the HepB-alum vaccine group.

Because the study was designed to measure noninferiority, it is impossible to extrapolate that the HepB-CpG vaccine is superior to the HepB-alum vaccine. “Rather, we can say that HepB-CpG vaccine did not have a higher rate of acute MI compared to HepB-alum, or that there was no association between then-vaccine type and MI,” author Katia Bruxvoort, PhD, MPH, an epidemiologist at the University of Alabama Birmingham, told Contagion. “These safety findings are thus aligned with the current guidelines that either vaccine can be used for most adults.”

The results of the single trial that found a higher incidence of acute MI events in participants taking the HepB-CpG vaccine were not statistically significant, Bruxvoort told Contagion, and the overall rates of MI were lower than expected. In addition, the MI events occurred in participants who had significant cardiovascular risk factors, meaning the results likely were due to random variation.

Bruxvoort pointed out that the Advisory Committee on Immunization Practices (ACIP) now recommends hepatitis B vaccination for all adults between the ages of 19 and 59, and aged 60 and over based on risk factors. “Because HepB-CpG vaccine is a 2-dose vaccine administered over 2 months compared to a 3-dose vaccine over 6 months, and we know from our previous work that series completion for the 2-dose vaccine is higher than for the 3-dose vaccine, HepB-CpG may be a good option to help scale up adult hepatitis B vaccination coverage,” she said.