Effect of Influenza Vaccination in Patients with Cardiovascular Disease: An Updated Meta-Analysis of Randomized Controlled Trials

Background: Influenza is a major cause of morbidity and mortality in patients with cardiovascular disease (CVD). The aim of this updated systematic review and meta-analysis was to evaluate the effect of influenza vaccination (IV) on morbidity and morbidity in adult patients with CVD. Methods: We conducted a systematic review and meta-analysis (PubMed, Cochrane Library, International Clinical Trials Registry Platform, and manual search of conference presentations) of randomized clinical trials published up to April 2022 analyzing whether IV reduced all-cause mortality in adult patients with CVD, including heart failure (HF) and coronary artery disease (CAD), compared with patients who were not vaccinated. Results: A total of six clinical trials comprising 9316 patients were analyzed. Five trials included CAD patients, and one trial included HF patients. Mean follow-up was 16 ± 9.7 months. Influenza vaccine was associated with a reduction of mortality compared to controls: relative risk (RR) 0.67, 95% confidence interval (95% CI), 0.47-0.95; p = 0.03; I2 = 53%, and with reduction of cardiovascular death compared to controls: RR 0.64; 95% CI 0.44-0.94; p = 0.02; I2 = 54%. There was a non-statistically significant reduction in myocardial infarction compared to control: RR 0.82, 95% CI 0.60-1.12; p = 0.57; I2 = 0%. Conclusion: In this meta-analysis of six randomized controlled clinical trials, IV was associated with a 33% and 36% relative risk reduction of all-cause mortality and cardiovascular death, respectively, in patients with CVD. We sought to promote consensus about the persistent benefits of influenza vaccination in patients with CVD by including two new clinical trials in CAD and HF, confirming the association of vaccination with risk reduction in subjects with CVD.