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

Abstract

IMPORTANCEThe 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 PARTICIPANTSThis 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 69 625 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. RESULTSOf the 31 183 recipients of HepB-CpG vaccine (median age, 49 years; IQR, 38-56 years), 51.2% (n = 15 965) were men, and 52.7% (n = 16 423) were Hispanic. Of the 38 442 recipients of HepB-alum (median age, 49 years; IQR, 39-56 years), 50.8% (19 533) were men, and 47.1% (n = 18 125) 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, −ϱ to 1.32], which was below the noninferiority margin; P < .001 for noninferiority). CONCLUSIONS AND RELEVANCEIn 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.

Universal hepatitis B vaccination in adults aged 19–59 years: Updated recommendations of the advisory committee on immunization practices—United States, 2022

“…The 2‐dose HepB vaccine (Heplisav‐B) was approved by FDA in 2017 and recommended by ACIP in 2018. No difference in occurrence of serious adverse events (GRADE evidence type 1; high certainty evidence) was found for Heplisav‐B compared with a 3‐dose vaccine (Engerix‐B), and serious adverse events were rare for both vaccines 8,9 …”

Data Errors

“…The Original Investigation titled “Association Between 2-Dose vs 3-Dose Hepatitis B Vaccine and Acute Myocardial Infarction,” published in the April 5, 2022, issue of JAMA , had data errors. In the primary analysis in the Abstract and Results section, the infinity symbol should have been negative.…”