A comprehensive cohort study found that COVID-19 vaccination was generally associated with a lower incidence of cardiovascular events, with some rare exceptions.

In the study, published in Nature Communications, investigators analyzed the data of 45.7 million adults residing England from December 2020 to January 2022 to assess the cardiovascular safety of different COVID-19 vaccine doses and brands used in the UK vaccination program. All of the individuals included in the study were eligible for first-dose analyses, 37.3 million of them were eligible for second-dose analyses, and 35.9 million of them were eligible for booster dose analyses. The vaccines studied were ChAdOx1, BNT-162b2, and mRNA-1273.

The study, led by investigators from the University of Cambridge, University of Bristol, and other institutions utilized longitudinal electronic health records from the NHS England Secure Data Environment. The data encompassed primary care, hospital admissions, COVID-19 testing and vaccination records, dispensed medication records, and death registrations.

The investigators used Cox regression to estimate adjusted hazard ratios (HR) and corresponding 95% confidence intervals (CI) for various cardiovascular events in time intervals since vaccination. The analysis adjusted for a wide range of comorbidities, age, sex, and prior COVID-19 infections.

Among the key findings were:

• The incidence of common arterial thrombotic events (mainly acute myocardial infarction and ischemic stroke) was generally lower following each vaccine dose, brand, and combination.
• Similarly, the incidence of common venous thrombotic events (mainly pulmonary embolism and lower limb deep venous thrombosis) was lower following vaccination.
• Previously reported rare harms were observed. Vaccine-induced thrombotic thrombocytopenia occurred after first ChAdOx1 vaccination and myocarditis and pericarditis occurred after first, second, and transiently after booster mRNA vaccination (BNT-162b2 and mRNA-1273).

Arterial Thrombotic Events:

• Adjusted HRs for composite arterial thrombotic events 13 to 24 weeks after first vaccine dose = 0.99 (95% CI = 0.97–1.02) for ChAdOx1 and 0.90 (0.88–0.93) for BNT-162b2
• Adjusted HRs after second doses = 0.73 (0.70–0.76) for ChAdOx1 and 0.80 (0.77–0.83) for BNT-162b2
• Adjusted HRs for mRNA booster vaccination after primary course of ChAdOx1 = 0.71 (0.66–0.76) 13 to 24 weeks after BNT-162b2 and 0.67 (0.62–0.72) 5 to 24 weeks after mRNA-1273.

Venous Thrombotic Events:

• Adjusted HRs for composite venous thrombotic events 13 to 24 weeks after first vaccine doses = 0.94 (95% CI 0.90–0.98) for ChAdOx1 and 0.85 (0.81–0.88) for BNT-162b2
• Adjusted HRs after second doses = 0.68 (0.63–0.73) for ChAdOx1 and 0.77 (0.72–0.83) for BNT-162b2
• Adjusted HRs for mRNA booster vaccination after primary course of ChAdOx1 = 0.63 (0.54–0.74) 13 to 24 weeks after BNT-162b2 and 0.55 (0.47–0.65) 5 to 24 weeks after mRNA-1273

Rare Adverse Events:

• Intracranial venous thrombosis: higher incidence immediately after first dose of ChAdOx1 (adjusted HR = 5.92, 95% CI = 4.07–8.63 at 2 weeks postvaccination)
• Thrombocytopenia: higher incidence after first dose of ChAdOx1 (adjusted HR = 2.07, 95% CI = 1.67–2.58 at 2 weeks postvaccination)
• Myocarditis: higher incidence after first dose of BNT-162b2 (adjusted HR = 2.05, 95% CI = 1.28–3.29 at 1 week postvaccination) and after second dose (adjusted HR = 3.14, 95% CI = 2.04–4.85 at 1 week postvaccination)
• Pericarditis: higher incidence after first dose of ChAdOx1 (adjusted HR = 1.74, 95% CI = 1.04–2.91 at 2 weeks postvaccination) and after second dose of BNT-162b2 (adjusted HR = 2.42, 95% CI = 1.62–3.62 at 3 to 4 weeks postvaccination).

The study's strengths included its large sample size, comprehensive analysis of different vaccine combinations, and extensive adjustment for potential confounding factors. However, limitations included potential residual confounding and the inability to adjust for time-varying postbaseline factors that may have influenced vaccination receipt and outcomes.

The researchers noted that these findings, in conjunction with the known long-term higher risk of severe cardiovascular complications associated with COVID-19, provided evidence regarding the cardiovascular effects of COVID-19 vaccination. They suggested that the results could inform future vaccination programs and public health guidelines.

This findings provided data on the cardiovascular safety of COVID-19 vaccines, offering information to health care providers and the public while confirming the rare but known complications associated with specific vaccine brands.

Ethics declarations are available in the study.