PPV23 Vaccination and Risk of Cardiovascular Events: A Meta-Analysis.

BACKGROUND: Prior observational studies have suggested that 23-valent pneumococcal polysaccharide vaccination (PPV23) may be associated with lower cardiovascular risk, but whether this association persists in randomized trials and adjusted observational studies remains uncertain. OBJECTIVES: This study evaluated whether PPV23 vaccination is associated with reduced risk of acute coronary syndrome (ACS) events, stroke, and all-cause mortality using evidence from randomized trials and propensity-adjusted observational studies. METHODS: MEDLINE, Embase, and Cochrane CENTRAL were systematically searched from inception to October 10, 2025. The authors included randomized controlled trials and observational cohort studies using propensity-based adjustment that compared PPV23 with placebo or no vaccination and reported ACS events, stroke, or all-cause mortality. Two reviewers independently extracted data and assessed risk of bias. Random-effects Bayesian and frequentist meta-analyses were used to pool HRs with 95% credible intervals (CrIs) or CIs. RESULTS: Six studies, including 2 randomized trials and 4 propensity-adjusted cohort studies were included. In the Bayesian analysis, the pooled HR for ACS events was 0.87 (95% CrI: 0.64-1.14), corresponding to an 85% posterior probability of any benefit, although the CrI and prediction interval indicated substantial uncertainty. Bayesian estimates did not suggest benefit for stroke (HR: 1.10; 95% CrI: 0.83-1.48) or all-cause mortality (HR: 1.02; 95% CrI: 0.83-1.29). Frequentist analyses were directionally consistent, with 95% CIs crossing the null for ACS events, stroke, and all-cause mortality. The certainty of evidence by Grading of Recommendations Assessment, Development and Evaluation was low across all outcomes. CONCLUSIONS: Current evidence remains insufficient to establish a cardiovascular benefit of PPV23. Further adequately powered evidence is needed to resolve the remaining uncertainty.