The 27,204 cohort members were observed for a total of 26,444 person-years, of which 8,847 (33.5%) person-years had received PPV23 in prior 5 years.
Mean age of study subjects when study started was 71.7 (SD: 8.6) years-old and 44.6% were male. Vaccinated group were significantly older, had more outpatient visits, had a much higher proportion of influenza vaccination and had more comorbidities than the unvaccinated group (Table ).
Baseline Characteristics of 27,204 cohort members according to their Pneumococcal vaccination status before the study started
During the 12-month follow-up, a validated episode of community acquired pneumonia was observed in 207 cases, a validated episode of acute myocardial infarction was observed in 130 cases and a validated episode of ischaemic stroke was observed in 121 cases. There was an incidence (per 1000 person-years) of 7.9 (95% CI: 6.9-9.0) for pneumonia, 4.9 (95% CI: 4.2-5.9) for myocardial infarction and 4.6 (95% CI: 3.8-5.5) for ischaemic stroke. Of the 27,204 cohort members, 840 died during study period (39 deaths from myocardial infarction/stroke). All-cause mortality rate was 31.8 per 1000 person-years (95% CI: 29.7-34.0), whereas specific mortality rates was 1.5 per 1000 (95% CI: 1.1-2.0) for myocardial infarction/stroke.
In the unadjusted analysis, we observed 63 episodes of pneumonia in 8,824 vaccinated person-years (7.1 per 1000 person-years) compared with 144 events in 17,546 unvaccinated person-years (8.2 per 1000 person-years). For myocardial infarction, there were 41 episodes of myocardial infarction in 8,830 vaccinated person-years (4.6 per 1000 person-years) compared with 89 events in 17,565 unvaccinated person-years (5.1 per 1000 person-years). For stroke, there were 30 events in 8,835 vaccinated person-years (3.4 per 1000 person-years) compared with 91 events in 17,559 unvaccinated person-years (5.2 per 1000 person-years). The unadjusted all-cause mortality rates were 26.1 and 34.6 per 1000 person-years among vaccinated and unvaccinated subjects, respectively.
In the multivariable analyses, despite vaccinated people had lower incidence rates than unvaccinated people, we found no evidence for an association between pneumococcal vaccination and risk of pneumonia (adjusted hazard ratio [HR]: 0.85; 95% CI: 0.62-1.15; p = 0.287) or myocardial infarction (adjusted HR: 0.83; 95% CI: 0.56-1.22; p = 0.347), but vaccination emerged significantly associated with a reduced risk of ischaemic stroke (adjusted HR: 0.65; 95% CI: 0.42-0.99; p = 0.048).
Although vaccinated subjects had lower all-cause mortality rates than unvaccinated subjects in the unadjusted analysis, vaccination was not associated with reduced risk of all-cause mortality in the multivariable analysis (adjusted HR: 0.88; 95% CI: 0.75-1.03; p = 0.118).
Table shows the values of unadjusted and adjusted analyses for the different outcomes. The covariate pneumococcal vaccine has proportional hazards in all the models. Footnotes in table indicate those predictor variables statistically significant (p < 0.05) or confounders in the final multivariable models.
Incidence and Risk of hospitalization for community acquired pneumonia (CAP), acute myocardial infarction (AMI), ischaemic stroke and death from any cause among patients 60 years or older in relation to pneumococcal-vaccination statusa
In a separate analysis including only immunocompetent people n = 24,278 persons, the results did not substantially vary. Among these subjects, with multivariable adjustment, pneumococcal vaccination did not emerge significantly effective against pneumonia (adjusted HR: 0.84; 95% CI: 0.59-1.19; p = 0.319), myocardial infarction (adjusted HR: 0.83; 95% CI: 0.55-1.25; p = 0.363) or death from any cause (adjusted HR: 0.84; 95% CI: 0.68-1.02; p = 0.083), but it was associated with a significant reduction in the risk of ischaemic stroke adjusted HR: 0.63; 95% CI: 0.40-0.99; p = 0.049).
Analyses restricted to persons with possible immunocompromise (n = 2,926 subjects) showed, in general, poor results. Among these subjects, we did not observe any significant protective effect of vaccination against pneumonia (adjusted HR: 0.92; 95% CI: 0.47-1.81; p = 0.811), myocardial infarction (adjusted HR: 0.81; 95% CI: 0.25-2.66; p = 0.732), ischaemic stroke (adjusted HR: 0.75; 95% CI: 0.23-2.41; p = 0.628) or death from any cause (adjusted HR: 0.99; 95% CI: 0.75-1.30; p = 0.941).
Analyses excluding people with history of prior coronary artery disease (n = 1,733 persons) or stroke (n = 1,294 persons), did not substantially vary the results.
In the analyses including exclusively 25,471 subjects without history of coronary artery disease, we observed 30 episodes of myocardial infarction in 8,236 vaccinated person-years (3.6 per 1000 person-years) compared with 48 events in 16,510 unvaccinated person-years (2.9 per 1000 person-years). This means that pneumococcal vaccination was not associated with significant reductions in the risk of myocardial infarction in the unadjusted analysis (HR: 1.25; 95% CI: 0.79-1.98; p = 0.344) neither in the multivariable analysis (adjusted HR: 1.12; 95% CI: 0.69-1.82; p = 0.660).
Among the 25,910 subjects without history of prior stroke, we observed 13 episodes of ischaemic stroke in 8,366 vaccinated person-years (1.6 per 1000 person-year) compared with 60 events among 16,810 unvaccinated person-years (3.6 per 1000 person-years), which pointed to a significant reduction in the risk of ischaemic stroke among vaccinated subjects in the unadjusted analysis (HR: 0.43; 95% CI: 0.24-0.79; p = 0.006). Multivariable analysis confirmed this association (adjusted HR: 0.46; 95% CI: 0.25-0.85; p = 0.013).
In the total study population, according to incidence data among vaccinated and unvaccinated subjects for the different outcomes, number needed to vaccinate for preventing one case of ischaemic stroke was 560 vaccinations (95% CI: 295 to 5,649). If we consider pneumonia and myocardial infarction, although the results did not reach statistical significance, number needed to vaccinate were 938 and 2,365 vaccinations, respectively (Table ).
Numbers needed to vaccinate for preventing one case of community acquired pneumonia, acute myocardial infarction or ischaemic stroke by pneumococcal vaccination in people 60 years or older