Frobert O, Gotberg M, Erlinge D, et al. Influenza Vaccination After Myocardial Infarction: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial. Circulation. 2021 Nov 2;144(18):1476-1484. doi: 10.1161/CIRCULATIONAHA.121.057042. Epub 2021 Aug 30. (Original study)

BACKGROUND: Observational and small, randomized studies suggest that influenza vaccine may reduce future cardiovascular events in patients with cardiovascular disease.

METHODS: We conducted an investigator-initiated, randomized, double-blind trial to compare inactivated influenza vaccine with saline placebo administered shortly after myocardial infarction (MI; 99.7% of patients) or high-risk stable coronary heart disease (0.3%). The primary end point was the composite of all-cause death, MI, or stent thrombosis at 12 months. A hierarchical testing strategy was used for the key secondary end points: all-cause death, cardiovascular death, MI, and stent thrombosis.

RESULTS: Because of the COVID-19 pandemic, the data safety and monitoring board recommended to halt the trial before attaining the prespecified sample size. Between October 1, 2016, and March 1, 2020, 2571 participants were randomized at 30 centers across 8 countries. Participants assigned to influenza vaccine totaled 1290 and individuals assigned to placebo equaled 1281; of these, 2532 received the study treatment (1272 influenza vaccine and 1260 placebo) and were included in the modified intention to treat analysis. Over the 12-month follow-up, the primary outcome occurred in 67 participants (5.3%) assigned influenza vaccine and 91 participants (7.2%) assigned placebo (hazard ratio, 0.72 [95% CI, 0.52-0.99]; P=0.040). Rates of all-cause death were 2.9% and 4.9% (hazard ratio, 0.59 [95% CI, 0.39-0.89]; P=0.010), rates of cardiovascular death were 2.7% and 4.5%, (hazard ratio, 0.59 [95% CI, 0.39-0.90]; P=0.014), and rates of MI were 2.0% and 2.4% (hazard ratio, 0.86 [95% CI, 0.50-1.46]; P=0.57) in the influenza vaccine and placebo groups, respectively.

CONCLUSIONS: Influenza vaccination early after an MI or in high-risk coronary heart disease resulted in a lower risk of a composite of all-cause death, MI, or stent thrombosis, and a lower risk of all-cause death and cardiovascular death, as well, at 12 months compared with placebo. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02831608.

Discipline Area Score
Internal Medicine 7 / 7
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Cardiology 6 / 7
Comments from MORE raters

Cardiology rater

This only confirms a Class I recommendation that is already standard of care.

Cardiology rater

This RCT has important implications for cardiologists because it provides high-quality evidence to support more frequent recommendations about receiving the influenza vaccine.

Family Medicine (FM)/General Practice (GP) rater

Yet another reason to vaccinate people!

Family Medicine (FM)/General Practice (GP) rater

Supports an obvious supposition that may encourage high vaccination rates.

General Internal Medicine-Primary Care(US) rater

In this double-blind controlled study, 2571 patients with a recent acute MI were given influenza immunization or placebo. There was a significant decrease in the rates of death and cardiovascular death, but not MI recurrence. This study was done during the Covid epidemic when influenza rates were low and suggests that in a regular year this effect would be even greater.

Internal Medicine rater

Looks like the flu is associated with clots also. Interesting that lining up the vaccine well with the circulating virus seemed to make a difference.
Comments from EvidenceAlerts subscribers

Mr. Leon Petruniak (11/4/2021 11:38 AM)

A large study across several geographic regions during a global health crisis. Perhaps a signal, but too many confounders for me to accept this paper's claims.