Clinical Research Study|Articles in Press

Influenza Vaccination to Prevention Therapy for Stable Coronary Artery Disease and Acute Coronary Syndrome: A Meta-Analysis of Randomized Trials

Published:February 19, 2023DOI:



      Influenza can cause a significant burden on patients with coronary artery disease. This meta-analysis assessed the effectiveness of influenza vaccination in patients with acute coronary syndrome and stable coronary artery disease.


      We searched the Cochrane Controlled Register of Trials (CENTRAL), Embase, MEDLINE,, and the World Health Organization International Clinical Trials Registry Platform from inception to September 2021. Estimates were summarized using the Mantel-Haenzel method and a random-effects model. To assess heterogeneity the I² statistic was used.


      Five randomized trials, comprising 4187 patients, were included, 2 of which included patients with acute coronary syndrome and 3 that included patients with stable coronary artery disease and acute coronary syndrome. Influenza vaccination significantly reduced the risk for all-cause mortality (relative risk [RR] = 0.56; 95% confidence interval [CI], 0.38-0.84), cardiovascular mortality (RR = 0.54; 95% CI, 0.37-0.80), major acute cardiovascular events (RR = 0.66; 95% CI, 0.49-0.88), and acute coronary syndrome (RR = 0.63; 95% CI, 0.44-0.89). On subgroup analysis, influenza vaccination remained effective for these outcomes in acute coronary syndrome but did not meet statistical significance in coronary artery disease. Furthermore, influenza vaccination did not reduce the risk for revascularization (RR = 0.89; 95% CI, 0.54-1.45), stroke or transient ischemic attack (RR = 0.85; 95% CI, 0.31-2.32), or heart failure hospitalization (RR = 0.91; 95% CI, 0.21-4.00).


      Influenza vaccine is a cheap and effective intervention to reduce the risk for all-cause mortality, cardiovascular mortality, major acute cardiovascular events, and acute coronary syndrome among coronary artery disease patients, especially in those with acute coronary syndrome.


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        • Roth GA
        • Mensah GA
        • Johnson CO
        • et al.
        Global burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study.
        J Am Coll Cardiol. 2020; 76: 2982-3021
        • Corrales-Medina VF
        • Madjid M
        • Musher DM
        Role of acute infection in triggering acute coronary syndromes.
        Lancet Infect Dis. 2010; 10: 83-92
      1. World Health Organization (WHO). Global influenza strategy 2019-2030. Available at: Accessed October 5, 2022.

        • Phrommintikul A
        • Kuanprasert S
        • Wongcharoen W
        • Kanjanavanit R
        • Chaiwarith R
        • Sukonthasarn A
        Influenza vaccination reduces cardiovascular events in patients with acute coronary syndrome.
        Eur Heart J. 2011; 32: 1730-1735
        • Keshtkar-Jahromi M
        • Vakili H
        • Rahnavardi MT
        The efficacy of influenza vaccination in reducing cardiovascular events in patients with coronary artery diseases: IVCAD study.
        Clin Microbiol Infect. 2009; 15: S395-S396
        • Ciszewski A
        • Bilinska ZT
        • Brydak LB
        • et al.
        Influenza vaccination in secondary prevention from coronary ischaemic events in coronary artery disease: FLUCAD study.
        Eur Heart J. 2008; 29: 1350-1358
        • Gurfinkel EP
        • Leon de la Fuente R
        • Mendiz O
        • Mautner B
        Flu vaccination in acute coronary syndromes and planned percutaneous coronary interventions (FLUVACS) Study.
        Eur Heart J. 2004; 25: 25-31
        • Fröbert O
        • Götberg M
        • Erlinge D
        • et al.
        Influenza vaccination after myocardial infarction: a randomized, double-blind, placebo-controlled, multicenter trial.
        Circulation. 2021; 144: 1476-1484
        • Maniar YM
        • Al-Abdouh A
        • Michos ED
        Influenza vaccination for cardiovascular prevention: further insights from the IAMI trial and an updated meta-analysis.
        Curr Cardiol Rep. 2022; 24: 1327-1335
        • Page MJ
        • McKenzie JE
        • Bossuyt PM
        • et al.
        The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.
        BMJ. 2021; 372: n71
        • Udell JA
        • Zawi R
        • Bhatt DL
        • et al.
        Association between influenza vaccination and cardiovascular outcomes in high-risk patients: a meta-analysis.
        JAMA. 2013; 310: 1711-1720
        • Davis MM
        • Taubert K
        • Benin AL
        • et al.
        Influenza vaccination as secondary prevention for cardiovascular disease: a science advisory from the American Heart Association/American College of Cardiology.
        J Am Coll Cardiol. 2006; 48: 1498-1502
        • Collet JP
        • Thiele H
        • Barbato E
        • et al.
        2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation.
        Eur Heart J. 2021; 42: 1289-1367
        • Fonseca HAR
        • Furtado RHM
        • Zimerman A
        • et al.
        Influenza vaccination strategy in acute coronary syndromes: the VIP-ACS trial.
        Eur Heart J. 2022; 43: 4378-4388
        • Rodrigues BS
        • Alves M
        • Duarte GS
        • Costa J
        • Pinto FJ
        • Caldeira D
        The impact of influenza vaccination in patients with cardiovascular disease: an overview of systematic reviews.
        Trends Cardiovasc Med. 2021; 31: 315-320
        • Kinlay S
        • Ganz P
        Role of endothelial dysfunction in coronary artery disease and implications for therapy.
        Am J Cardiol. 1997; 80: 11I-16I
        • Conti CR
        Vascular events responsible for thrombotic occlusion of a blood vessel.
        Clin Cardiol. 1993; 16: 761-762
        • Hebsur S
        • Vakil E
        • Oetgen WJ
        • Kumar PN
        • Lazarous DF
        Influenza and coronary artery disease: exploring a clinical association with myocardial infarction and analyzing the utility of vaccination in prevention of myocardial infarction.
        Rev Cardiovasc Med. 2014; 15: 168-175
        • Bocale R
        • Necozione S
        • Desideri G
        The link between influenza and myocardial infarction: vaccination protects.
        Eur Heart J Suppl. 2022; 24: I84-I88
        • Naghavi M
        • Wyde P
        • Litovsky S
        • et al.
        Influenza infection exerts prominent inflammatory and thrombotic effects on the atherosclerotic plaques of apolipoprotein E-deficient mice.
        Circulation. 2003; 107: 762-768
      2. Centers for Disease Control and Prevention (CDC). FluVaxView: Influenza (Flu): Influenza vaccination coverage for persons 6 months and older. Available at: Accessed October 9, 2022.

      3. European Centre for Disease Prevention and Control (ECDC). Seasonal influenza vaccination and antiviral use in EU/EEA Member States: Overview of vaccine recommendations for 2017-2018 and vaccination coverage rates for 2015-2016 and 2016-2017 influenza seasons. Available at: Accessed February 20, 2023.

        • Toubasi AA
        • Al-Sayegh TN
        • Obaid YY
        • Al-Harasis SM
        • AlRyalat SAS
        Efficacy and safety of COVID-19 vaccines: a network meta-analysis.
        J Evid Based Med. 2022; 15: 245-262