Clinical Question

Does an influenza vaccine given shortly after acute myocardial infarction (MI) reduce the likelihood of death or cardiovascular events in the following year?

Bottom Line

The researchers found a clinically and statistically significant reduction in all-cause mortality for patients given an influenza vaccine immediately following an MI (number needed to treat [NNT] = 50). The results are consistent with those of several other studies and a meta-analysis of four randomized controlled trials and 12 observational studies. (Level of Evidence = 1b)

Synopsis

The study identified 2,571 adults in eight countries who were hospitalized with acute MI and had not received the influenza vaccine in the past 12 months. The patients were randomized to receive the influenza vaccine or placebo within 72 hours of admission or angiography. Participants were enrolled during the flu season (September through February in the northern hemisphere). The study was terminated before achieving the target enrollment of 4,372 patients because of the COVID-19 pandemic.

The primary outcome of death, MI, or stent thrombosis was based on a telephone interview 12 months after randomization. That is a potential limitation, although the authors performed a masked adjudication of any of these events after reviewing medical records. Groups were similar at baseline with a mean age of 60 years, 81% were men, and 54% had ST-elevation MI. There were more patients with two-vessel disease in the vaccine group (25.2% vs. 21.7%) and correspondingly fewer with one-vessel disease. The composite of all-cause mortality, stent thrombosis, and recurrent MI was less frequent in the vaccine group (5.0% vs. 7.2%; hazard ratio = 0.72; 95% CI, 0.52 to 0.99; NNT = 45). Most of this difference was due to significantly lower rates of all-cause mortality (2.9% vs. 4.9%; NNT = 50) and cardiovascular mortality (2.7% vs. 4.5%; NNT = 56). There was no significant difference between the vaccine and placebo groups with regard to MI (2.0% vs. 2.4%) or stent thrombosis (0.5% vs. 0.2%). There were some subgroup differences, with greater benefit seen for nonsmokers, those without a previous MI, and with non–ST-elevation MI. There was a large benefit for the 2017–2018 and 2019–2020 influenza seasons, but not for the 2016–2017 and 2018–2019 seasons. This was likely because the match between the vaccine and the circulating influenza strains was better in those two seasons. Harms were limited to mild injection site reactions. Industry support and participation were limited to provision of the influenza vaccine. Adverse effects were rare and similar between groups. Approximately one in seven patients in both groups reported seeking an influenza vaccine outside of the trial.

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry and foundation

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Reference: Fröbert O, Götberg M, Erlinge D, et al. Influenza vaccination after myocardial infarction: a randomized, double-blind, placebo-controlled, multicenter trial. Circulation. 2021;144(18):1476-1484.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.