The two-dose hepatitis B vaccine is not associated with an increased risk of acute MI

According to the CDC, the hepatitis B virus (HBV) affects approximately 296 million people worldwide.¹ This includes more than 6 million children under the age of 5.¹ Hepatitis B is a serious liver infection caused by HBV, and every 30 seconds someone dies from hepatitis-related illness.²

The Advisory Committee on Immunization Practices (ACIP) recommends that the following people be vaccinated against HBV³:

All infants

Unvaccinated people under the age of 19

Adults from 19 to 59 years old

Adults 60 years and older with risk factors for HBV

The World Health Organization’s goal is to eliminate hepatitis B by 2030. A white paper published by the World Hepatitis Alliance includes recommendations for preventing mother-to-child transmission,⁴ such as screening in early pregnancy and education provided as a standard of prenatal care.⁴ ACIP also released updated recommendations in 2022 that people 60 and older without risk factors for HBV can also receive the vaccine.⁵ The recommendations emphasize that health care providers should offer the vaccine to this population rather than waiting for patients to request it.⁵

HBV vaccine with cytosine phosphoguanine adjuvant (HepB-CpG vaccine; Heplisav-B) is a 2-dose series of vaccines approved for adults 18 years of age and older.⁶ In clinical studies, Heplisav-B has been shown to produce greater seroprotection than HBV at 3 doses with an aluminum hydroxide adjuvant (HepB-alun vaccine; Engerix-B).⁶ Engerix-B is approved for vaccination at birth and for pediatric and adult patients.⁶ A previous clinical trial reported a higher number of acute myocardial infarctions (MI) in patients receiving Heplisav-B (0.25%) than in those vaccinated with Engerix-B (0.04%).⁶ Heplisav-B was approved in 2017 and the FDA required a post-marketing study to assess the risk of acute MI.⁶

Hepatitis B vaccine and acute MI

The post-marketing study was conducted at Kaiser Permanente Southern California (KPSC) to compare rates of acute MI between people receiving Heplisav-B and Engerix-B.⁶ The prospective non-inferiority cohort study used a non-randomized cluster design to distribute HBV vaccines to KPSC medical centers.⁶ The people included in the study were at least 18 years of age or older.⁶ These individuals must have received at least 1 dose of HBV vaccine from August 7, 2018 to October 31, 2019 during a family medicine or internal medicine visit. Additionally, this was the time and setting where over 90% of HBV vaccines were administered.⁶ Patients on dialysis were excluded from the study.

Study participants were followed through the electronic health record system for 13 months. There were 31,183 patients included in the Heplisav-B group and 38,442 study participants in the Engerix-B group.⁶ The median age in both groups was 49 years.

During the study follow-up period, 74 potential acute MI events occurred in the Heplisav-B group and 128 in the Engerix-B group.⁶ In addition, 52 events were classified as acute MI type 1 (certain or probable) in the Heplisav-B group.⁶ There were 71 events classified as acute MI type 1 in the Engerix-B group.⁶ In addition, the rate per 1000 person-years of acute MI type 1 was 1.67 in the Heplisav-B group and 1.86 in the Engerix-B group.⁶ An analysis was performed to compare the incidence of acute MI type 1 between groups. Kaplan-Meier analysis (survival analysis) revealed that the cumulative incidence of acute MI type 1 events was similar between the groups (P = 0.56).⁶

The researchers pointed out several limitations of the study, such as the possibility of misclassification of vaccine exposure.⁶ However, the manufacturer and batch number information has been verified against the brand name. In addition, dose record reviews were also conducted. Possible misclassification of acute MI was also a limitation, but two cardiologists reviewed all the data.⁶

The study researchers concluded that there was no increased risk of acute MI with the Heplisav-B vaccine compared to the Engerix-B vaccine.⁶ These results were consistent across all subgroups defined by age group, diabetes, hypertension, receipt of concomitant vaccines, and whether the index dose (first dose during the study period) was the first HBV vaccine or subsequent vaccine.⁶

The references:

1. Quick facts about global hepatitis B. CDC. Updated July 27, 2022. Accessed February 27, 2023. https://www.cdc.gov/globalhealth/immunization/diseases/hepatitis-b/data/fast-facts.html

2. World Hepatitis Day 28 July. Global Hepatitis Alliance. Revised March 30, 2022. Accessed March 3, 2023. https://www.worldhepatitisday.org/

3. Hepatitis B questions and answers for healthcare professionals. CDC. Accessed February 27, 2023. https://www.cdc.gov/hepatitis/hbv/hbvfaq.htm

4. Mothers and Babies Can’t Wait: A Call to Action to End Mother-to-Child Transmission of Hepatitis B. World Hepatitis Alliance. Accessed March 3, 2023. https://www.worldhepatitisalliance.org/news/pmtctreport/

5. Weng MK, Doshani M, Khan MA, et al. Universal Hepatitis B Vaccination in Adults 19-59 Years of Age: Updated Recommendations from the Advisory Committee on Immunization Practices – United States, 2022. MMWR Morb Mortal Wkly Rep 2022;71(13):477 -483. doi: 10.15585/mmwr.mm7113a1

6. Bruxvoort K, Slezak J, Qian L, et al. Association between 2-dose versus 3-dose hepatitis B vaccine and acute myocardial infarction. JAMA. 2022;327(13):1260-1268. doi: 10.1001/jama.2022.2540