Study Evaluates Risk of Acute Myocardial Infarction With 2-Dose vs 3-Dose Hepatitis B Vaccine
An earlier clinical trial found a higher number of acute myocardial infarction events in those administered HepB-CpG vaccine versus those administered the HepB-alum vaccine.
Administration of the 2-dose hepatitis B virus (HBV) vaccine with a cytosine phosphoguanine adjuvant (HepB-CpG vaccine; Heplisav-B) has been found to produce higher seroprotection in prelicensure trials compared with the 3-dose HBV vaccine with an aluminum hydroxide adjuvant (HepB-alum vaccine; Engerix-B).
However, a clinical trial found a higher number of acute myocardial infarction (MI) events in those administered HepB-CpG vaccine versus those administered the HepB-alum vaccine. To assess this risk, a study published in JAMA evaluated the rate of acute MI between recipients of HepB-CpG vaccine versus the HepB-alum vaccine.
The investigators conducted the prospective cohort noninferiority study at Kaiser Permanente Southern California (KPSC), which is an integrated health care system with approximately 4.7 million members. The investigators evaluated 69,625 adults who were not undergoing dialysis and who were administered at least 1 dose of the HBV vaccine at KPSC from August 7, 2018, to October 31, 2019.
The first dose administered during the study accrual period was considered the index dose. Patients were included in the study even if the index dose was not the first dose of an HBV vaccine that they had received. Patients were followed up via electronic health record from their index date until the first occurrence of the outcome, disenrollment from KPSC, death, or 13 months, whichever occurred first.
Patients were followed for 13 months following the initial dose of the HBV vaccine for occurrence of type 1 acute MI, with potential events identified using diagnosis codes and adjudicated by cardiologists. The investigators estimated the adjusted hazard ratio (HR) of acute MI by comparing recipients of HepB-CpG vaccine versus recipients of HepB-alum vaccine, with inverse probability of treatment weighting (IPTW) to adjust for demographic and clinical characteristics.
Among 31,183 individuals administered the HepB-CpG vaccine, the median age was 49 years; (IQR, 38-56 years), 51.2% (n = 15,965) were male, and 52.7% (n = 16,423) were Hispanic. Among 38,442 individuals administered HepB-alum, the median age was 49 years (IQR, 39-56 years), 50.8% (19,533) were male, and 47.1% (n = 18,125) were Hispanic. The researchers noted that the characteristics were well-balanced between both cohorts after IPTW.
The study showed 52 type 1 acute MI events confirmed among recipients of the HepB-CpG vaccine, which translated to a rate of 1.67 per 1000-person-years compared with 71 type 1 acute MI events confirmed among recipients of the 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).
The investigators noted that the findings were consistent across subgroups defined by age group, diabetes, hypertension, and receipt of concomitant vaccines and by whether the index dose was the first or subsequent HBV vaccine dose.
The study authors noted several limitations, the first of which was a potential misclassification of the vaccine exposure; however, the manufacturer and lot number descriptions were checked against the brand name, and a chart review of doses with potential discrepancies was conducted.
Secondly, misclassification of acute MI outcome was also possible; however, all potential events were adjudicated by at least 2 cardiologist reviewers, according to the study. They also noted there were more events from claims outside the KPSC health system among those administered the HepB-alum vaccine, with a lower proportion adjudicated as definite or probable type 1 acute MI.
They added that the HR for acute MI comparing recipients of the HepB-CpG vaccine versus the HepB-alum vaccine would have been even lower if some events adjudicated as not acute MI were instead true acute MI.
The researchers concluded that administration of the HepB-CpG vaccine did not meet the statistical criterion for increased risk of acute MI compared with the HepB-alum vaccine.
Bruxvoort K, Slezak J, Qian L, et al. Association Between 2-Dose vs 3-Dose Hepatitis B Vaccine and Acute Myocardial Infarction. JAMA. 2022;327(13):1260–1268. doi:10.1001/jama.2022.2540