Effect of the adult pneumococcal polysaccharide vaccine on cardiovascular disease: a systematic review and meta-analysis.

Animal models and clinical studies suggest a mechanistic link between the pneumococcal polysaccharide vaccine (PPV) and a cardiovascular protective effect. However, conflicting results exist from several large observational studies in humans. We set out to systematically review current literature and conduct meta-analyses of studies on PPV and cardiovascular outcomes. Medline, Embase and CENTRAL were searched for randomised controlled trials (RCTs) and observational studies in adults, using PPV as the intervention, up to 30 April 2014. Studies that compared PPV with a control (another vaccine, no vaccine or placebo) and recorded ischaemic events were included in this review. Two investigators extracted data independently on study design, baseline characteristics and summary outcomes. Study quality was examined using the Newcastle-Ottawa Quality Assessment Scale. Pooled estimates using random effects models and their 95% CIs were calculated separately for the outcomes of acute coronary syndrome (ACS) events and stroke. No RCT data were available. A total of 230 426 patients were included in eight observational studies and recorded as ACS events. PPV was associated with significantly lower odds of ACS events in patients 65 years and older (pooled OR=0.83 (95% CI 0.71 to 0.97), I(2)=77.0%). However, there was no significant difference in ACS events when younger people were included (pooled OR=0.86 (95% CI 0.73 to 1.01), I(2)=81.4%). Pooling of four studies, covering a total of 192 210 patients, did not find a significantly reduced risk of stroke in all patients (pooled OR=1.00 (95% CI 0.89 to 1.12), I(2)=55.3%), or when restricted to those 65 years and older (pooled OR=0.96 (95% CI 0.87 to 1.05), I(2)=22.5%). In this meta-analysis of observational studies, the use of PPV was associated with a significantly lower risk of ACS events in the older population, but not stroke. An adequately powered and blinded RCT to confirm these findings is warranted.