Enhanced Estimates of the Influenza Vaccination Effect in Preventing Mortality: A Prospective Cohort Study

Mortality is a major end-point in the evaluation of influenza vaccine effectiveness. However, this effect is not well known, since most previous studies failed to show good control of biases. We aimed to estimate the effectiveness of influenza vaccination in preventing all-cause mortality in community-dwelling seniors. Since 2009, a population-based cohort study using healthcare databases has been conducted in Navarra, Spain. In 2 late influenza seasons, 2011/2012 and 2012/2013, all-cause mortality in the period January to May was compared between seniors (65 years or over) who received the trivalent influenza vaccine and those who were unvaccinated, adjusting for demographics, major chronic conditions, dependence, previous hospitalization, and pneumococcal vaccination. The cohort included 103,156 seniors in the 2011/2012 season and 105,140 in the 2012/2013 season (58% vaccinated). Seniors vaccinated in the previous season who discontinued vaccination (6% of the total) had excess mortality and were excluded to prevent frailty bias. The final analysis included 80,730 person-years and 2778 deaths. Vaccinated seniors had 16% less all-cause mortality than those unvaccinated (adjusted rate ratio [RR] = 0.84; 95% confidence interval 0.76–0.93). This association disappeared in the post-influenza period (adjusted RR = 0.96; 95% confidence interval 0.85–1.09). A similar comparison did not find an association in January to May of the 2009/2010 pandemic season (adjusted RR = 0.98; 95% confidence interval 0.84–1.14), when no effect of the seasonal vaccine was expected. On average, 1 death was prevented for every 328 seniors vaccinated: 1 for every 649 in the 65 to 74 year age group and 1 for every 251 among those aged 75 and over. These results suggest a moderate preventive effect and a high potential impact of the seasonal influenza vaccine against all-cause mortality. This reinforces the recommendation of annual influenza vaccination in seniors.