Influenza vaccination and risk for cardiovascular events: a nationwide self-controlled case series study

Sen, Abhijit; Bakken, Inger Johanne; Govatsmark, Ragna Elise Støre; Varmdal, Torunn; Bønaa, Kaare Harald; Mukamal, Kenneth Jay; Håberg, Siri Eldevik; Janszky, Imre

BACKGROUND: US and European guidelines diverge on whether to vaccinate adults who are not at high risk for cardiovascular events against influenza. Here, we investigated the associations between influenza vaccination and risk for acute myocardial infarction, stroke and pulmonary embolism during the 2009 pandemic in Norway, when vaccination was recommended to all adults. METHODS: Using national registers, we studied all vaccinated Norwegian individuals who suffered AMI, stroke, or pulmonary embolism from May 1, 2009 through September 30, 2010. We defined higher-risk individuals as those using anti-diabetic, anti-obesity, anti-thrombotic, pulmonary or cardiovascular medications (i.e. individuals to whom vaccination was routinely recommended); all other individuals were regarded as having lower-risk. We estimated incidence rate ratios with 95% CI using conditional Poisson regression in the pre-defined risk periods up to 180 days following vaccination compared to an unexposed time-period, with adjustment for season or daily temperature. RESULTS: Overall, we observed lower risk for cardiovascular events following influenza vaccination. When stratified by baseline risk, we observed lower risk across all three outcomes in association with vaccination among higher-risk individuals. In this subgroup, relative risks were 0.72 (0.59–0.88) for AMI, 0.77 (0.59–0.99) for stroke, and 0.73 (0.45–1.19) for pulmonary embolism in the period 1–14 days following vaccination when compared to the background period. These associations remained essentially the same up to 180 days after vaccination. In contrast, the corresponding relative risks among subjects not using medications were 4.19 (2.69–6.52), 1.73 (0.91–3.31) and 2.35 (0.78–7.06). CONCLUSION: In this nationwide study, influenza vaccination was associated with overall cardiovascular benefit. This benefit was concentrated among those at higher cardiovascular risk as defined by medication use. In contrast, our results demonstrate no comparable inverse association with thrombosis-related cardiovascular events following vaccination among those free of cardiovascular medications at baseline. These results may inform the risk–benefit balance for universal influenza vaccination.