Thromboembolic risk in non-anticoagulated atrial fibrillation patients with valvular heart disease and low CHA2DS2-VASc scores: are these patients truly low risk of stroke?

Abstract Background Patients with atrial fibrillation and valvular heart disease (VHD) beyond moderate-to-severe mitral stenosis and/or a mechanical prosthetic valve, so-called EHRA Type 2 VHD, have been associated with a higher risk of thromboembolism compared with patients with atrial fibrillation and no VHD. A minor but important proportion of patients with atrial fibrillation and EHRA Type 2 VHD has 0 or 1 coexisting CHA2DS2-VASc stroke risk factors, and are therefore not strongly recommended oral anticoagulant therapy according to guidelines. Whether these patients are “truly low” risk of stroke has not been investigated. We aimed to describe the risk of thromboembolism in non-anticoagulated atrial fibrillation patients with and without EHRA Type 2 VHD and with 0 or 1 non-sex comorbidity of the CHA2DS2-VASc score. Methods Cohort study of atrial fibrillation patients with and without EHRA Type 2 VHD identified in nationwide Danish registries from 2000–2018. 1-year risk of thromboembolism was estimated for the study population divided into four subgroups in relation to non-sex CHA2DS2-VASc score comorbidities (except for previous thromboembolism) and age category (<65 or 65–74 years). Results We identified 1,907 and 53,707 incident atrial fibrillation patients with and without EHRA Type 2 VHD. Median age was 57 years and 55 years in patients with and without EHRA Type 2 VHD and 0 comorbidities and 67 years in patients with and without EHRA Type 2 VHD and 1 comorbidity. Percentage of females was approximately 44% in patients with and without EHRA Type 2 VHD and 0 comorbidities and 33% and 36% in patients with and without EHRA Type 2 VHD and 1 comorbidity. In patients with 1 comorbidity, the most prevalent stroke risk factor of the CHA2DS2-VASc score was hypertension. Cumulative incidence of thromboembolism according to presence of EHRA Type 2 VHD and age category in patients with 0 or 1 non-sex comorbidity of the CHA2DS2-VASc score are presented in the figure (the curve for patients with EHRA Type 2 VHD aged 65–74 years and with 0 comorbidities was omitted due to few events). At 1 year after atrial fibrillation diagnosis, patients with and without EHRA Type 2 VHD aged <65 or 65–74 years and with 0 or 1 comorbidity of the CHA2DS2-VASc score had a risk of thromboembolism ranging 1.3–2.2% and 0.5–1.7% according to age category and number of comorbidities of the CHA2DS2-VASc score. In patients with EHRA Type 2 VHD aged <65 years with 0 or 1 comorbidity, the risk was 1.5% and 2.2% at 1 year after the diagnosis of atrial fibrillation. Conclusion In atrial fibrillation patients with EHRA Type 2 VHD, we observed a risk of thromboembolism that may exceed the level above which oral anticoagulation is considered beneficial. No trial has specifically examined patients with EHRA Type 2 VHD and low CHA2DS2-VASc scores and, therefore, our observations may be important to patients who are not recommended oral anticoagulant therapy according to contemporary guidelines. Figure 1. Cumulative incidence of thromboembolism Funding Acknowledgement Type of funding source: Private company. Main funding source(s): The study was supported by “The BMS/Pfizer European Thrombosis Investigator Initiated Research Program (ERISTA) 2018” and the Obel Family Foundation.