Risk of adverse events in non-anticoagulated european and asian patients with atrial fibrillation and clinical complexity: an analysis from two prospective observational registries

Abstract Background Atrial fibrillation (AF) is often accompanied by clinical complexity (CC), a condition characterized by multiple comorbidities, which increase both thromboembolic and bleeding risks. In this setting, the clinical benefit of oral anticoagulation (OAC) might be uncertain. Purpose To assess the risk of adverse events in patients with Atrial Fibrillation and CC based on OAC use. Methods Post-hoc analysis of two prospective observational registries, from Europe and Asia. CC was defined as the presence of a CHA2DS2-VASc ≥2 and at least 2 of the following: age ≥75 years, body mass index ≤ 23/kg/m2, bleeding history and chronic kidney disease. Logistic regression was used to identify factors associated with OAC use. Cox regression analyses were used to calculate hazard ratios (HRs) and 95% CIs for the risk of adverse events in AF CC patients on OAC compared to non-OAC. The primary outcome was a composite of all-cause death (ACD) and major adverse cardiovascular events (MACE). Secondary outcomes were each component of the primary outcome and major bleeding (MB). Exploratory analyses investigated the risk of each MACE component (cardiovascular death, acute coronary syndrome or thromboembolic events). Interaction analysis was performed to investigate ethnic-related differences. Results We included 2029 AF CC patients (80.2±6.3 years, 48.6% females), of whom 355 were non-OAC and 1674 on OAC. AF CC non-OAC patients were older and had a higher cardiovascular burden compared to those on OAC. Logistic regression showed that antiplatelets, paroxysmal AF, advanced age, cancer, prior bleeding and dementia were linked to lower likelihood of being prescribed OAC whereas vascular disease was associated with higher OAC use. After a median follow up of 392 (IQR 346-729) days, the following outcomes occurred: 488 (24.1%) primary outcomes, including 392 (19.3%) ACD and 255 (12.6%) MACE. AF CC patients not on OAC had significantly higher incidence of MACE, MB, acute coronary syndrome, thromboembolic events and cardiovascular death compared to those on OAC. After adjustment for confounders, AF CC non-OAC patients had a higher risk of the primary outcome (HR 1.71, 95%CI 1.28-2.27), ACD (HR 1.98, 95%CI 1.47-2.66), MACE (HR 1.61, 95%CI 1.06-2.44) and cardiovascular death (HR 2.47, 95%CI 1.51-4.02), while the risk of MB was not different compared to patients on OAC (Table 1, Figure 1). On interaction analyses, no ethnic-related differences were found except for age that had a greater impact on the risk of both primary outcome (HR 1.06, 95%CI 0.41-2.73 vs HR 1.64, 95%CI 0.98-2.73, Pint=0.054) and ACD (HR 1.02, 95%CI 0.98-1.07 vs HR 2.81, 95%CI 1.13-6.99, Pint=0.045) when comparing Asians to Europeans. Conclusions AF CC non-OAC patients face a higher risk of death, cardiovascular death and thrombotic events, while their hemorrhagic risk is comparable to those on OAC, underscoring the need for safer therapies to prevent thrombosis without increasing bleeding.