Association Between Influenza Vaccination and Cardiovascular Outcomes in High-Risk Patients: A Meta-analysis | Cardiology | JAMA | JAMA Network
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Original Investigation
October 23/30, 2013

Association Between Influenza Vaccination and Cardiovascular Outcomes in High-Risk Patients: A Meta-analysis

Author Affiliations
  • 1Women’s College Research Institute and Cardiovascular Division, Department of Medicine, Women’s College Hospital, University of Toronto, Toronto, Ontario, Canada
  • 2Medical University of the Americas, Nevis, West Indies
  • 3VA Boston Healthcare System, Harvard Medical School, Boston, Massachusetts
  • 4Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 5Clinical Research and Development Center, Shahid Modarres Medical Center, Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University (MC), Tehran, Iran
  • 6Division of Infectious Disease, Department of Medicine, Pennsylvania State University School of Medicine, Hershey
  • 7Institute of Psychiatry, King’s College London, London, United Kingdom
  • 8South London and Maudsley National Health Service Foundation Trust, London, United Kingdom
  • 9Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
  • 10Institute of Cardiology, Warsaw, Poland
  • 11Cardiovascular Research Center, Shahid Modarres Medical Center, Shahid Beheshti University (MC), Tehran, Iran
  • 12Peter Munk Cardiac Centre, University Health Network, Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, University of Toronto, Toronto, Ontario, Canada
JAMA. 2013;310(16):1711-1720. doi:10.1001/jama.2013.279206

Importance  Among nontraditional cardiovascular risk factors, recent influenzalike infection is associated with fatal and nonfatal atherothrombotic events.

Objectives  To determine if influenza vaccination is associated with prevention of cardiovascular events.

Data Sources and Study Selection  A systematic review and meta-analysis of MEDLINE (1946-August 2013), EMBASE (1947-August 2013), and the Cochrane Library Central Register of Controlled Trials (inception-August 2013) for randomized clinical trials (RCTs) comparing influenza vaccine vs placebo or control in patients at high risk of cardiovascular disease, reporting cardiovascular outcomes either as efficacy or safety events.

Data Extraction and Synthesis  Two investigators extracted data independently on trial design, baseline characteristics, outcomes, and safety events from published manuscripts and unpublished supplemental data. High-quality studies were considered those that described an appropriate method of randomization, allocation concealment, blinding, and completeness of follow-up.

Main Outcomes and Measures  Random-effects Mantel-Haenszel risk ratios (RRs) and 95% CIs were derived for composite cardiovascular events, cardiovascular mortality, all-cause mortality, and individual cardiovascular events. Analyses were stratified by subgroups of patients with and without a history of acute coronary syndrome (ACS) within 1 year of randomization.

Results  Five published and 1 unpublished randomized clinical trials of 6735 patients (mean age, 67 years; 51.3% women; 36.2% with a cardiac history; mean follow-up time, 7.9 months) were included. Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs 4.7%; RR, 0.64 [95% CI, 0.48-0.86], P = .003) in published trials. A treatment interaction was detected between patients with (RR, 0.45 [95% CI, 0.32-0.63]) and without (RR, 0.94 [95% CI, 0.55-1.61]) recent ACS (P for interaction = .02). Results were similar with the addition of unpublished data.

Conclusions and Relevance  In a meta-analysis of RCTs, the use of influenza vaccine was associated with a lower risk of major adverse cardiovascular events. The greatest treatment effect was seen among the highest-risk patients with more active coronary disease. A large, adequately powered, multicenter trial is warranted to address these findings and assess individual cardiovascular end points.