Association Between Influenza Vaccination and Cardiovascular Outcomes in High-Risk Patients

Abstract

Among nontraditional cardiovascular risk factors, there remains interest in a potential association between respiratory tract infections, of which influenza and influenzalike illnesses are common causes,^1,2 and subsequent cardiovascular events.^3-9 Prior studies suggest that seasonal influenzalike illnesses may explain a major determinant of the timing of acute thrombotic vascular events in patients with previously stable coronary artery disease (CAD) and cerebrovascular disease.³ Further supporting this hypothesis, several epidemiological studies have suggested a strong inverse longitudinal relationship between influenza vaccination and the risk of fatal and nonfatal cardiovascular events.^4,10-19 A few small randomized clinical trials (RCTs) have explicitly tested whether influenza vaccination may reduce the risk of cardiovascular events with large treatment effects.^20-24 Based largely on observational findings, medical association guidelines recommend universal vaccination in patients with, or at risk of, cardiovascular disease for protection from general influenza complications.^25-27 Cardiovascular associations specifically recommended influenza vaccination for the secondary prevention of ischemic heart disease in 2006 based on the earliest reported RCT.^28-31 Because of the potential for confounding in an observational study of this subject^32-34 and because prior meta-analyses included observational studies but omitted a systematic review of all influenza vaccination randomized trials,^7,35,36 we set out to perform a systematic review and meta-analysis of all randomized clinical trials of influenza vaccine that studied cardiovascular events as efficacy or safety outcomes.