COVID Shots Tied to Lower Risks of Heart Attack, Cardiac Death

COVID-19 vaccines were associated with a lower risk of major adverse cardiovascular events (MACE), in addition to other outcomes, particularly among older adults, according to three studies.

Among over 1 million veterans who received the 2024-2025 COVID vaccine, vaccine effectiveness was 37.7% (95% CI 18.2-54.9) for preventing COVID-associated MACE, a composite endpoint of cardiovascular death, myocardial infarction, stroke, and heart failure hospitalization, with a risk difference per 10,000 people of 2.04 (95% CI 0.85-3.65) versus those who didn’t get a COVID vaccine, reported Ziyad Al-Aly, MD, of the VA St. Louis Health Care System, and colleagues in JAMA Internal Medicine.

Looking at each endpoint, COVID vaccination was 57.9% effective at preventing COVID-associated cardiovascular death (95% CI 25.2-78.2), with a risk difference of 1.0 per 10,000 people (95% CI 0.3-2.1). Vaccination was 38.5% effective against COVID-associated myocardial infarction (95% CI 4.3-62.3), and 41.9% effective against COVID-associated hospitalization for heart failure (95% CI 4.1-67.5).

In a subgroup analysis by age, vaccine effectiveness for COVID-associated MACE was statistically significant only in those older than 75 years, with a vaccine effectiveness of 50.7% (95% CI 31.8-65.6). This group also had the largest absolute risk reduction (5.48 fewer events per 10,000 people).

Secondary analyses showed that vaccination was also linked with lower risks for all-cause MACE, hospitalization, or death.

Despite widespread immunity through COVID infection and vaccination, “our study findings show that vaccination continues to provide protection against associated cardiovascular outcomes,” Al-Aly and colleagues wrote. “The magnitude of this vaccine effectiveness, however, is lower than estimates from the early phase of the vaccine rollout.”

More Studies, More Vaccine Benefits

The 2024-2025 vaccines also demonstrated effectiveness against COVID-associated emergent care, hospitalization, and critical illness among adults in the 7 to 299 days after vaccination, reported Ryan Wiegand, PhD, of the CDC’s National Center for Immunization and Respiratory Diseases, and colleagues in JAMA Internal Medicine.

Estimated vaccine effectiveness was 26% against emergency department/urgent care visits (95% CI 23-29), 35% against hospitalization (95% CI 30-40), and 41% against critical illness (95% CI 28-51). Vaccine effectiveness rates were basically identical for people ages 65 and older.

For immunocompromised adults, estimated vaccine effectiveness was 24% against COVID-associated hospitalization (95% CI 13-34).

“For practicing clinicians, these results affirm that annual COVID-19 vaccination continues to meaningfully reduce the risk of severe outcomes, especially in the first 6 months after vaccination and among patients at highest risk,” Wiegand and colleagues wrote.

Finally, a European case-control study published in JAMA Network Open showed that the 2025-2026 COVID vaccines mirrored the performance of the prior season’s shots. Among older patients, overall COVID vaccine effectiveness against symptomatic disease was 59% (95% CI 14-83).

Cardiovascular Benefits ‘Much Greater’ Than Risks

Given the drop in COVID deaths and disability, “it should no longer be treated as exceptional but as one of many infectious diseases for which vaccination is protective,” noted former FDA Commissioner Robert Califf, MD, of Duke University School of Medicine in Durham, North Carolina, in an accompanying editorial in JAMA Internal Medicine.

“The important issue for clinical decision-making is whether the clearly demonstrated modest benefit is worth the cost or the risk of rare adverse effects,” he wrote, “because the absolute beneficial difference in serious outcomes such as hospitalization and death is lower in younger populations.”

For cardiovascular risk-benefit calculations, the results are clear: “Taken together, these reports offer convincing evidence that the cardiovascular benefits of vaccination for COVID-19 are much greater than the risks, demonstrated or potential, that have been identified,” Califf added.

Overall, the new studies, alongside previous studies, “provide strong evidence of a favorable balance of benefit to risk for updated COVID-19 vaccine boosters across the population,” he wrote — although the differences are small, particularly in low-risk populations.

Vaccines Also Tied to Lower All-Cause MACE

To assess cardiovascular events that may have been driven by undiagnosed or untested SARS-CoV-2 infection, Al-Aly and team evaluated potential links between COVID vaccination and all-cause MACE, hospitalization, and death.

Vaccination was 6.2% effective against all-cause MACE (95% CI 3.8-8.9), with 23.7 fewer events per 10,000 people. Vaccine effectiveness was 6.6% against all-cause hospitalization (95% CI 4.4-9.1), with 29.9 fewer events per 10,000 people, and 7.1% against all-cause death (95% CI 3.9-10.5), with 15.8 fewer deaths per 10,000 people.

“Extrapolating these estimates to a population of 1 million people, vaccination could plausibly be associated with averting approximately 2,370 MACE events and 1,580 deaths over an 8-month period,” Al-Aly and colleagues wrote.

“Effectiveness extends to broader outcomes (all-cause MACE, hospitalization, and death), likely reflecting the hidden burden of undetected SARS-CoV-2 and associated complications that are reduced by COVID-19 vaccination,” they concluded.

Their study included 349,085 veterans who received same-day coadministration of a 2024-2025 COVID vaccine and a 2024-2025 seasonal influenza vaccine, and 690,574 veterans who received the flu vaccine only. Mean patient age was 70.1 years, and 91.8% were men.

Study limitations included the predominantly older, white, male U.S. veteran population, which may limit the findings’ generalizability. In addition, the researchers didn’t evaluate SARS-CoV-2 variant-specific vaccine effectiveness.