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.