Risk of worsening heart failure and all-cause mortality following mRNA COVID-19 vaccination in patients with heart failure: a Danish nationwide real-world safety study

Abstract

Abstract Background The studies investigating the safety and efficacy of the SARS-COV2 mRNA vaccines only included a limited number of heart failure patients and no separate analyses were performed regarding the safety of the vaccines in this patient population. Purpose The aims of this study were to investigate the risk of worsening heart failure and all-cause mortality associated with the SARS-COV-2 mRNA vaccines in a nationwide cohort of patients with heart failure. Methods Using the Danish nationwide registries, two cohorts were constructed; 1) all prevalent heart failure patients in 2019 and 2) all prevalent heart failure patients in 2021 who were vaccinated with either of the two mRNA vaccines (BNT162B2 or mRNA-1273). The patients in the two cohorts were matched 1:1 using exact exposure matching on age, sex, and duration of heart failure (intervals). For patients in the 2021 cohort, the index date was defined as the date of the patients' second vaccination. Patients in the 2019 cohort were assigned the index day and month of their 1:1 match in the 2021 cohort, but used the pre-vaccination index year 2019. The primary outcomes were worsening heart failure and all-cause mortality and secondary outcomes were myocarditis and venous thromboembolism. Standardized risks were estimated based on outcome-specific Cox regression analyses, and all models were standardized to age, sex, duration of heart failure, use of SGLT2 inhibitors or Entresto, ischemic heart disease, cancer, diabetes, atrial fibrillation, and admission with heart failure <90 days before index. Results The total study population comprised 101,786 patients, with 50,893 patients in each cohort. The median age of the study population was 74 (interquartile range (IQR); 66,81), and duration of heart failure was 4.1 (IQR: 2.0,6.7) years. The standardized risk of all-cause mortality within 90 days was 2.2% (95% CI: 2.1% to 2.4%) in the 2021 cohort and 2.6% (95% CI: 2.4% to 2.7%) in the 2019 cohort, showing a significantly lower risk difference for all-cause mortality in 2021 versus 2019 (risk difference: −0.3% (95% CI: −0.5% to −0.1%)) Figure 1)). The standardized risk of worsening heart failure within 90 days was 1.1% (95% CI: −1.0% to 1.2%) in the 2021 cohort and 1.1% (95% CI: 1.0% to 1.2%) in the 2019 cohort showing no significant difference in the risk of worsening heart failure between the two cohorts (risk difference: 0% (95% CI: −0.1% to 0.1%)). No significant differences were found for venous thromboembolism or myocarditis. Conclusion This study showed that the SARS-COV2 mRNA vaccines were not associated with an increased risk of worsening heart failure, venous thromboembolism or myocarditis, but was associated with a decreased risk of all-cause mortality. Our study may suggest that these vaccines are safe in heart failure patients. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Heart FoundationLæge Sofus Carl Emil Friis og hustrus legat