Reassuring Data on Two-Dose Hep B Vaccine, Risk of Acute MI

There was no higher risk of heart attack for recipients of the two-dose hepatitis B cytosine phosphoguanine adjuvant vaccine (Heplisav-B) compared to the three-dose hepatitis B vaccine with an aluminum hydroxide adjuvant (Engerix-B), a prospective study found.

Among nearly 70,000 adults who received at least one hepatitis B vaccine dose, type 1 acute myocardial infarctions (MIs) occurred at a rate of 1.67 per 1,000 person-years for those who received the two-dose vaccine and 1.86 per 1,000 person-years for recipients of the three-dose vaccine, which met noninferiority criteria (adjusted HR 0.92, one-sided 97.5% CI ∞ to 1.32, P<0.001), reported Katia Bruxvoort, PhD, of the University of Alabama at Birmingham, and colleagues in JAMA.

Clinical trials showed that the two-dose vaccine led to significantly greater seroprotection, which was also achieved earlier than the three-dose vaccine. However, one clinical trial found the two-dose vaccine was also associated with a greater number of MIs, Bruxvoort’s group noted. Of those, participants who experienced acute MIs had greater cardiovascular risk factors at baseline, while the events occurred randomly without a “temporal relationship to vaccination,” they added.

The FDA approved Heplisav-B in November 2017 but required a postmarket trial at Kaiser Permanente Southern California (KPSC) due to safety concerns surrounding the risk of MI and immune-mediated diseases.

For their study, the researchers examined electronic health records data from 69,625 adults who received at least one hepatitis B vaccine dose at KPSC from Aug. 7, 2018 to Oct. 31, 2019. Those who received an index dose of the two-dose vaccine (n=31,183) or the three-dose vaccine (n=38,442) at the internal medicine or family medicine department of the integrated healthcare system were included. Excluded were those undergoing dialysis.

To assess the risk of type 1 acute MI, participants were followed up until the first occurrence of an acute MI, disenrollment from KPSC, death, or after 13 months.

Inverse probability treatment weighting adjusted for socio-demographics and clinical characteristics. Two cardiologists confirmed acute MI events, which could be adjudicated by a third cardiologist.

Median patient age was 49, just over half were men, and roughly half were Hispanic. In the year prior to their index dose of a hepatitis B vaccine, 58-59% had diabetes, 41-42% had dyslipidemia, and 42-44% had a Charlson Comorbidity index score of 1. Nearly one-quarter had obesity, while only 0.4-0.5% had had an acute MI. Nearly two-thirds were on cardiovascular disease medication in the year prior to their index vaccine dose. Nearly half (47-49%) received other vaccines concomitantly with their index dose.

At follow-up, 52 of 74 potential acute MI events were confirmed type 1 MIs in the two-dose vaccine group versus 71 of 128 in the three-dose vaccine group.

The authors acknowledged limitations to the data, including the potential for misclassifying vaccine exposures or acute MI diagnoses.