Patients with atrial fibrillation and common exclusion criteria from clinical trials are at high risk of clinical events: The Murcia AF Project II (MAFP-II) cohort study

Abstract Background: Some clinical characteristics and comorbidities in atrial fibrillation (AF) patients are common exclusion criteria in randomized clinical trials (RCTs) investigating oral anticoagulation. However, these characteristics are present in real-world patients. We compared the risk of adverse clinical outcomes between patients with and without RCT exclusion criteria. Methods: The Murcia AF Project II (MAFP-II) cohort study was an observational study including AF outpatients starting vitamin K antagonist (VKA) therapy from July, 2016 to June, 2018. For the selection of the exclusion criteria, the four pivotal RCTs of direct-acting oral anticoagulants (DOACs) were used as reference. During 2-years of follow-up, ischemic strokes/transient ischemic attacks, major adverse cardiovascular events (MACEs), major bleeds, and all-cause deaths, were recorded. Results: 1050 patients (51.5% female, median age 77 years) were included, of whom 368 (35%) met at least one exclusion criterion for RCTs. During follow-up, the incidence rate ratios for major bleeding, MACE and all-cause mortality were higher among patients with exclusion criteria (all p<0.001). Patients fulfilling at least one exclusion criterion had increased risks of major bleeding (aHR 1.48; 95% CI 1.22-1.81; p<0.001), MACE (aHR 1.51, 95% CI 1.10-2.09, p=0.012), and mortality (aHR 3.22, 95% CI 2.32-4.48, p<0.001), as well as a lower event-free survival (all log-rank p<0.001) Conclusions: In this real-world AF cohort of patients taking VKAs, more than one-third had at least one RCT exclusion criteria, which translates into an increased risk of major bleeding, MACE, and death. The outcomes of RCT on anticoagulation may not be applicable to all AF patients.