Mortality, cardiovascular and bleeding risk according to anticoagulant type in patients with atrial fibrillation and cancer. Insights from the Nationwide Italian START registry

Background. The optimal management of anticoagulation in atrial fibrillation (AF) patients with cancer remains unclear. Beyond thromboembolism these patients have an increased risk of cardiovascular events (CVEs) and bleeding due to their frailty condition. We investigated all-cause mortality, CVEs and any bleeding risk comparing direct oral anticoagulants (DOACs) and vitamin K antagonists (VKA). Methods. AF Patients with cancer from the nationwide Italian START registry on treatment with oral anticoagulants were included. A propensity score matching (PSM) was performed. Results were expressed as hazard ratio (HR) and their 95% confidence interval (95%CI) for all-cause mortality using Cox regression analysis and as subdistribution HR (sHR) and their 95%CI for CVEs and bleeding risk taking account of competing risk using Fine-Gray analysis. Results. 1,605 of 10,369 AF patients had cancer (median 78 years, 44.7% women). During a median follow-up of 729.8±597.4 days, 153 deaths, 177 CVEs and 90 bleedings occurred. After PSM, DOACs were associated with lower all-cause mortality (HR: 0.37, 95%CI: 0.23-0.58, p<0.001) and CVEs (sHR 0.58, 95%CI 0.39-0.84, p=0.005) risk, but not bleeding risk, compared to warfarin. These results were more evident if patients treated with VKAs had a low anticoagulation quality (Time in Therapeutic Range <70%). In the subgroup analysis, we found a lower risk of all-cause of death and CVEs in patients treated with apixaban and dabigatran, and a higher risk of any bleeding in patients treated with edoxaban compared to VKA. Conclusion: DOACs are associated with a lower mortality and CVEs risk compared to VKAs in patients with AF and cancer, without difference in bleeding risk.