Pneumococcal Polysaccharide Vaccination Does Not Reduce Rates of Cardiovascular Events

Twenty-three-valent pneumococcal polysaccharide vaccination (PPSV23; Pneumovax; Merck & Co) did not reduce rates of fatal and nonfatal acute coronary syndrome and ischemic stroke compared with placebo, according to results from a double-blind, placebo-controlled, parallel-arm, randomized clinical trial published in the Journal of the American Medical Association.¹

How Can Pneumococcal Vaccines Offer Cardioprotective Effects?

Vaccine-preventable respiratory diseases have been linked to an elevated risk of cardiovascular and cerebrovascular complications, heightening mortality and morbidity risk. Through exacerbating preexisting conditions or inducing new cardiac events, the mechanisms behind respiratory diseases can interplay with the complex functions of the cardiac system, causing unforeseen complications and burdens to patients. This is why it is paramount for individuals to receive routine vaccinations, especially if they are at a high risk of poor outcomes.²

Pneumococcal disease is no exception. Caused by the Streptococcus pneumoniae bacteria, research has found that up to 30% of patients admitted to hospitals with invasive pneumococcal disease (IPD) experience a major adverse cardiovascular event, including new or worsening heart failure and myocardial infarction (MI). Accordingly, pneumococcal vaccination has been shown to be cardioprotective, reducing the risk of MI and all-cause cardiovascular mortality.^3,4

Although investigations have examined the protective effects of pneumococcal vaccination in general, data is lacking on whether different pneumococcal vaccines can provide the same effects. Two different types of pneumococcal vaccines are used in the United States—PPSV23, which utilizes a sugar component to stimulate an immune response, and pneumococcal conjugate vaccines (PCVs), which utilize a protein carrier to stimulate immunity. While each vaccine offers protection against pneumococcal serotypes, whether they offer differing cardiovascular protection is unknown.^1,5

Can PPSV23 Specifically Provide Cardiovascular Protection?

Given the lack of randomized clinical trials on the subject, the current study authors sought to determine the cardioprotective effects specifically of PPSV. Specifically, they aimed to examine whether pneumococcal polysaccharide vaccination can protect against a composite primary outcome of fatal and nonfatal acute coronary syndrome and ischemic stroke in patients at increased cardiovascular risk, with average follow-up of 7 years post-immunization.¹

Patients were enrolled across 6 study centers in Australia from 2016 to 2017, with enrollees being community-dwelling adults aged 55 through 60 years at baseline. The patients had to harbor at least 2 risk factors for cardiovascular disease—such as obesity, hypertension, or hypercholesterolemia—but no prior cardiovascular event or indication for early pneumococcal vaccination. The authors analyzed the data between February 2023 and December 2024, utilizing competing risk proportional hazards regression models.¹

In total, 4725 participants (mean [SD] age, 58.0 [1.7] years) were included in the study and were randomized to receive either PPSV23 or placebo in the form of saline. According to the investigators, 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). Moreover, there were no significant differences regarding the exploratory outcomes of all-cause mortality, all-cause hospital presentations, and cardiovascular-related hospital procedures.¹

The investigators noted that the results were tempered by the lower-than-expected event rate, leading to underpowered results. Underpowered studies do not have a sufficiently large sample size to answer the question at hand. Therefore, further research—using larger samples and in a randomized format—is necessary to confirm the results garnered in this study. However, the data tentatively shine a light on the potential differences in cardiovascular protection among pneumococcal vaccines. A direct comparison between vaccines is essential for a more thorough elucidation of their purported cardiovascular protection.^1,6

REFERENCES

1. Hure A, Peel R, D’Este C, et al. Prevention of adverse cardiovascular events using the 23-valent pneumococcal polysaccharide vaccine: A randomized clinical trial. JAMA Cardiology. Published online September 17, 2025. doi:10.1001/jamacardio.2025.3043

2. Halpern L. Pneumococcal vaccination is underutilized in adults with high cardiovascular risk. Pharmacy Times. Published September 19, 2025. Accessed October 7, 2025. https://www.pharmacytimes.com/view/pneumococcal-vaccination-is-underutilized-in-adults-with-high-cardiovascular-risk

3. Africano HF, Serrano-Mayorga CC, Ramirez-Valbuena PC, et al. Major adverse cardiovascular events during invasive pneumococcal disease are serotype dependent. Clin Infect Dis. 2020;72(11):e711-e719. doi:10.1093/cid/ciaa1427

4. Jaiswal V, Peng Ang S, Lnu K, et al. Effect of pneumococcal vaccine on mortality and cardiovascular outcomes: A systematic review and meta-analysis. J Clin Med. 2022;11(13):3799. doi:10.3390/jcm11133799

5. Pneumococcal—Pneumococcal vaccine recommendations. CDC. Last Updated October 26, 2024. Accessed October 7, 2025. https://www.cdc.gov/pneumococcal/hcp/vaccine-recommendations/index.html

6. Case LD, Ambrosius WT. Power and sample size. Methods Mol Biol. 2007;404:377-408. doi:10.1007/978-1-59745-530-5_19