Original Article
Evaluating Clinical Effectiveness of Pneumococcal Vaccination in Preventing Stroke: The CAPAMIS Study, 3-Year Follow-up

https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.12.047Get rights and content

Background

Cerebrovascular benefits using the 23-valent pneumococcal polysaccharide vaccine (PPV23) are controversial. This study assessed clinical effectiveness of PPV23 in preventing ischemic stroke in people older than 60 years.

Methods

We conducted a population-based cohort study involving 27,204 individuals of 60 years or older in Tarragona, Spain, who were prospectively followed from December 01, 2008, until November 30, 2011. Outcomes were neuroimaging-confirmed ischemic stroke, 30-day mortality from stroke, and all-cause death. Pneumococcal vaccination effectiveness was evaluated by Cox regression analyses, estimating hazard ratios (HRs) adjusted for age, sex, comorbidities, and influenza vaccine status.

Results

Cohort members were followed for a total of 76,033 person-years, of which 29,065 were for vaccinated subjects. Overall, 343 cases of stroke, 45 deaths from stroke, and 2465 all-cause deaths were observed. Pneumococcal vaccination did not alter the risk of stroke (multivariable HR: 1.04; 95% confidence interval [CI]: .83-1.30; P = .752), death from stroke (HR: 1.14; 95% CI: .61-2.13; P = .686), and all-cause death (HR: .97; 95% CI: .89-1.05; P = .448). In analyses focused on people with and without a history of cerebrovascular disease, the PPV23 did not emerge effective in preventing any analyzed event, but influenza vaccine emerged independently associated with a reduced risk of death from stroke (HR: .51; 95% CI: .28-.93; P = .029) and all-cause death (HR: .73; 95% CI: .67-.81; P < .001).

Conclusions

Our data support that the PPV23 does not provide benefit against ischemic stroke, but it also supports a beneficial effect of influenza vaccine in reducing specific- and all-cause mortality risk in the general population older than 60 years.

Introduction

The use of the 23-valent polysaccharide pneumococcal vaccine (PPV23) is commonly recommended for high-risk adults and elderly people.1 Protective effects of vaccination against invasive pneumococcal disease have been clearly proved, whereas a possible effectiveness in preventing other clinically relevant outcomes remains more controversial.2

In recent years, because some studies reported an increasing risk of thrombotic events among patients with acute respiratory infections (including influenza and pneumonia),3, 4 it has been suggested that pneumococcal vaccination would protect patients from acute thrombotic events.5, 6 In the last decade, several studies have investigated this issue with conflicting results.7, 8, 9, 10, 11, 12, 13

If we concretely consider cerebrovascular thrombotic events, 3 retrospective studies using distinct health databases have evaluated the relationship between pneumococcal vaccination and the risk of stroke with nondefinitive results.7, 9, 12 Thus, considering that a potential effect of pneumococcal vaccination in preventing cerebrovascular disease could have large clinical implications, a prospective study using validated clinical data to clarify whether a protective effect of vaccination is real would be greatly needed.

In the authors' study region (Southern Catalonia, Spain), the PPV23 is recommended and publicly funded for people older than 60 years since 2003. Considering this, we designed a 3-year prospective cohort study, known as CAPAMIS (Community Acquired Pneumonia, Acute Myocardial Infarction and Stroke),14 with the major aim of evaluating clinical benefits from PPV23 use. An interim analysis at 12-month follow-up and a summarized research letter have been published.15, 16 This article reports the analyses of PPV23 effectiveness against ischemic stroke at the end of 36-month follow-up, assessing possible vaccination effectiveness as in primary prevention (people without a history of cerebrovascular disease) and in secondary prevention (patients with a history of stroke).

Section snippets

Design, Setting, and Study Population

Study design has been extensively described elsewhere.14 In brief, this is a closed cohort study that included all people assigned to 9 Primary Care Centers (PCCs) in the region of Tarragona, Spain, who were 60 years or older on December 1, 2008 (N = 27,204 individuals). Cohort members were followed from the start of the study (December 1, 2008) until the occurrence of a first episode of stroke, disenrollment from the PCC, death, or until the end of the study (November 30, 2011). The study was

Results

The 27,204 cohort members were observed for a total of 76,033 person-years, of which 29,065 (38%) person-years corresponded to vaccinated subjects. At the study start, 8981 cohort members were classified as vaccinated and 18,223 as unvaccinated. Of the 18,223 subjects initially considered as unvaccinated, 2390 (13%) received PPV23 later (contributing to the analyses with 3472 person-years in the nonvaccinated group and 3597 person-years in the vaccinated group).

The mean age of study subjects

Discussion

We undertook a large cohort study to assess the clinical effectiveness of the PPV23 in preventing stroke in older adults (main target population where PPV23 is recommended). To our knowledge, this is the first prospective study using validated clinical data to evaluate the potential role of pneumococcal vaccination in cerebrovascular prevention. As the main findings, our data show no benefit of PPV23 against incident and/or recurrent ischemic stroke, death from stroke, and all-cause death. In

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    Grant support: Funding for the study was provided by a grant from the “Fondo de Investigación Sanitaria” of the Instituto de Salud Carlos III (FIS 09/00043) of the Spanish Health Ministry.

    This study sponsor had no role in the design or implementation of the study, analysis of data, or reporting of the results.

    The work was performed at the Primary Care Service “Camp de Tarragona,” Institut Catala de la Salut, Tarragona, Spain.

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