Pneumococcal vaccination and risk of acute coronary syndromes in patients with pneumonia: population-based cohort study
- Dean T Eurich1,2,
- Jennie J Johnstone3,
- Jasjeet K Minhas-Sandhu2,
- Thomas J Marrie4,
- Sumit R Majumdar1,2,5
- 1Department of Public Health Sciences, School of Public Health, University of Alberta, Edmonton, Alberta, Canada
- 2ACHORD, 2-040 Li Ka Shing Center, University of Alberta, Edmonton, Alberta, Canada
- 3Department of Medicine, McMaster University, Hamilton, Ontario, Canada
- 4Department of Medicine, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
- 5Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
- Correspondence to Dr Dean Eurich, Associate Professor, 2-040 Li Ka Shing Center for Health Research Innovation, University of Alberta, Edmonton, AB T6G 2E1, Canada;
Contributors All authors contributed to the conception and design; DTE, JMS, JJ and SRM contributed to the analysis and interpretation of data; DTE, JJ and JMS drafted the article; all authors revised it critically for important intellectual content; and all authors provided final approval of the version to be published. All authors had full access to all of the data (including statistical reports and tables) in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
- Accepted 1 April 2012
Background It is vigorously debated whether pneumococcal polysaccharide vaccination (PPV) reduces risk of acute coronary syndrome (ACS) events in patients with community-acquired pneumonia (CAP).
Methods Clinical data were prospectively collected on a population-based cohort of adults presenting with CAP in Edmonton (Alberta, Canada). Multivariable Cox models and propensity matching were used to examine the association between PPV status and ACS events within 90 days of pneumonia. Sensitivity analyses related to PPV administration (before pneumonia vs after) and duration of benefit (90 days vs 1 year) were conducted to rule out confounding.
Results Overall, 6171 patients were included; mean age 59 (SD 21) years, 53% male subjects, 18% had ischaemic heart disease and 2738 (44%) were hospitalised. Within 90 days of pneumonia, ACS events occurred in 175 (3%) patients and most were non-fatal (162 (93%)). In multivariable analyses, PPV exposure was associated with a 58% reduction in ACS events (12 vs 16 events per 100 patient-years, adjusted HR (aHR) 0.42 (0.27 to 0.66)) and results were nearly identical with propensity matching (aHR 0.46 (0.28 to 0.73)). However, indepth sensitivity analyses, with some with large assumptions, could not refute the existence of a small protective benefit of PPV.
Conclusion Even after extensive adjustment using clinical data, the authors observed that PPV exposure was associated with a 60% reduction in ACS events among patients with pneumonia. Sensitivity analyses demonstrated that these findings, at least in part, were probably a result of confounding, most likely the ‘healthy-vaccinee’ effect. Previous observational studies using administrative data suggesting a very large protective benefit of PPV on ACS events may have been heavily confounded.
Funding DTE receives salary support from Alberta Heritage Foundation for Medical Research (AHFMR) and the Canadian Institutes for Health Research (CIHR). SRM receives salary support from AHFMR and holds an endowed chair in patient health management. TJM received Grants-in-aid from Capital Health; and unrestricted grants from Abbott Canada, Pfizer Canada and Janssen-Ortho Canada. The study sponsors played no role in study design or conduct; collection, analysis, interpretation of data; writing of the report; or in the decision to submit the paper for publication. All authors declare that DTE, JJ, JMS, TJM, SRM have no non-financial interests that may be relevant to the submitted work.
Competing interests None.
Ethical approval Ethical approval for the study was obtained from The Health Research Ethics Board of the University of Alberta approved the study (approval number pro00004999).
Provenance and peer review Not commissioned; internally peer reviewed.