Prevention of Adverse Cardiovascular Events Using the 23-Valent Pneumococcal Polysaccharide Vaccine: A Randomized Clinical Trial.

Importance Animal studies and meta-analysis of human observational data suggest that pneumococcal polysaccharide vaccination (PPV) could be protective against atherosclerosis; however, to the authors' knowledge, no randomized clinical trial has been conducted. Objective To determine whether pneumococcal vaccination (Pneumovax [Merck Sharp & Dohme Corp]) decreases the composite primary outcome of fatal and nonfatal acute coronary syndrome and ischemic stroke in people at increased risk, with an average follow-up of 7 years after immunization. Design, Setting, and Participants This was a double-blind, placebo-controlled, parallel-arm randomized clinical trial conducted at 6 centers across Australia. Participants were community-dwelling adults 55 to 60 years of age at baseline in 2016 to 2017, with at least 2 risk factors (obesity, hypertension, or hypercholesterolemia) for cardiovascular disease (CVD) but no prior CVD event or indication for early pneumococcal vaccination. Data were analyzed from February 2023 to December 2024 using competing risk proportional hazards regression models, stratified by sex and center. Interventions Participants received either 23-valent PPV (PPV23) or placebo (saline). Main Outcomes and Measures The primary outcome was a composite of fatal and nonfatal myocardial infarction or ischemic stroke, ascertained via electronic medical records from emergency department, admitted patient, and mortality data collections using International Statistical Classification of Diseases, Tenth Revision, Australian Modification (ICD-10-AM) codes. Results A total of 4725 participants (mean [SD] age, 58.0 [1.7] years; 2433 male [52%]) were included in this study. There was no significant difference in the primary outcome (58 of 2366 events in the active PPV23 group compared with 64 of 2357 events in the control group, hazard ratio, 0.90; 95% CI, 0.63-1.28; P = .57). Similarly, no significant differences occurred in the exploratory outcomes of all-cause mortality, all-cause hospital presentations, and CVD-related hospital procedures. These results are tempered by the lower than expected event rate leading to low power. Conclusions and Relevance Results of this randomized clinical trial found that PPV23 did not reduce the rates of fatal and nonfatal acute coronary syndrome and ischemic stroke, although the study was underpowered. Trial Registration ANZCTR Identifier: ACTRN12615000536561.