Effects of Annual Influenza Vaccination on Winter Mortality in Elderly People With Chronic Heart Disease

Cinta de Diego; Angel Vila-Córcoles; Olga Ochoa; Teresa Rodriguez-Blanco; Elisabeth Salsench; Imma Hospital; Ferran Bejarano; M. del Puy Muniain; Mercé Fortin; Montserrat Canals and EPIVAC Study Group


Eur Heart J. 2009;30(2):209-216. 

In This Article


During the total study period, the 1340 cohort members were observed for an amount of 4027 person-years (209 968 person-weeks). The mean age when the study started was 76.2 years (SD: 7.1) and 47.4% were men. At baseline, 1068 (82.3%) of patients had some other form of co-morbidity, mostly hypertension (64.5%), diabetes mellitus (32.3%), or chronic lung disease (19.3%). Table 1 shows the characteristics of the Study Population when the study started (1 January 2002) according to the reception or non-reception of the influenza vaccine in the Autumn 2001. As it can be seen in Table 1, at the beginning of the study, vaccinated subjects were slightly older than non-vaccinated subjects (mean age: 76.7 vs. 75.5; P = 0.004), and they had more frequency of attendance and co-morbidity than non-vaccinated subjects.

Of the 1340 cohort members, 277 (20.7%) died during the total 40 months follow-up, and 16 (1.2%) moved during the study period. Figure 1 shows the survival of cohort members throughout the 40 months study period.

Figure 1.

A Survival Flow Chart of Cohort Members During the 40 Month Study Period

If we consider those cohort members who remained in the closed cohort at the beginning of each year (excluding patients who died or moved during the prior year), the annual vaccination coverage reached 64.2% in the winter 2002, 69.3% in 2003, 73.5% in 2004, and 72.3% in 2005. In total 83 196 person-weeks were observed within the overall January–April periods 2002–2005, of which 57 980 person-weeks (69.7%) were vaccinated and 25 216 person-weeks were non-vaccinated against influenza in the respective previous autumn.

The mean incidence rate of all-cause death throughout the total 40 months study period was 68.8 deaths per 1000 person-years (132 per 100 000 person-weeks). Mortality varied significantly throughout the months of the year. We observed 134 deaths within the influenza periods of January–April and 75 deaths during the reference summer periods (June–September).

Among the total 134 deaths occurring within January–April, cause-specific death was registered in the primary care clinical record in only 82 cases (61.2%). Among these 82 patients, the specific cause of death was a cardiovascular disorder in 28 cases (34.1%), a cancer in 24 cases (29.3%), a respiratory cause in seven cases (8.5%), an infectious cause in six cases (7.3%), and other causes in 17 cases (20.7%).

Considering the overall influenza periods 2002–2005, 85 deaths were observed among persons who had received the influenza vaccine in the prior autumn and 49 deaths among persons who had not received the vaccine in the previous autumn. This meant an all-cause mortality rate (per 100 000 person-weeks) of 146.6 (95% CI: 117–181) in vaccinated subjects and 194.3 (95% CI: 144–257) in non-vaccinated subjects. Table 2 shows the absolute number of deaths, mortality rates, and different results of the influenza vaccine's effectiveness in reducing mortality risk within the influenza periods (January–April) and within the reference non-influenza periods (June–September).

Unadjusted analysis showed that influenza vaccination was associated with a marginally significant decreasing rate of mortality within the overall influenza periods [hazard ratio (HR): 0.75; 95% CI: 0.52–1.06; P = 0.101], whereas it was not significant during the June–September control period (HR: 1.15; 95% CI: 0.68–1.90; P = 0.630).

Considering the sum of influenza periods 2002–2005, attributable risk among non-vaccinated subjects was 47.7 deaths per 100 000 person-weeks, so the number needed to vaccinate to save one death during one influenza period was 122 annual vaccinations (95% CI: 53 to infinite).

Multivariable analyses showed that annual vaccination was associated with a statistically significant reduction in the risk of all-cause mortality of 37% throughout the overall influenza periods 2002–2005 (adjusted HR: 0.63; 95% CI: 0.44–0.91; P = 0.013), whereas it was not significant during the reference summer period (adjusted HR: 0.94; 95% CI: 0.56–1.58; P = 0.814).

When we consider vaccine impact on winter mortality in each of the four analysed influenza seasons, the unadjusted protective effect of vaccination ranged from –8 to 40% (Table 3). Although the upper limit of the confidence interval did not reach statistical significance, we estimated that the numbers needed of annual vaccinations to save one death within each influenza period were 99 in the 2001–2002 influenza season, 455 in the 2002–2003 influenza season, 162 in the 2003–2004 influenza season, and 49 in the 2004–2005 influenza season.

Multivariable analysis showed that the adjusted effectiveness of vaccination against winter mortality varied between 20% in the 2002–2003 influenza season (adjusted HR: 0.80; 95% CI: 0.36–1.76; P = 0.572) to 54% in the 2001–2002 influenza season (adjusted HR: 0.46; 95% CI: 0.21–1.03; P = 0.059) (Table 3).

In supplementary analyses by sex, table not shown, vaccine effectiveness did not reach statistical significance in men. Vaccination effectiveness within the overall influenza period 2002–2005 was found in women (HR: 0.49; 95% CI: 0.30–0.78; P = 0.003). In stratified analyses by year, no statistically significant effect was observed in men, whereas a marginally significant effect was found in women in Winter 2002 (HR: 0.32; 95% CI: 0.10–1.04; P = 0.059) and 2005 (HR: 0.49; 95% CI: 0.23–1.02; P = 0.058).


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