PF340 PATIENTS WITH HIGHER BODY MASS INDEX TREATED WITH DIRECT / NON VITAMIN K DEPENDENT ANTICOAGULANTS (DOAC / NOAC) EXPERIENCE WORSE CLINICAL OUTCOMES
Authors: M. Lucijanic, I. Jurin, H. Jurin, B. Starcevic, M. Skelin, A. Glasnovic, I. Hadzibegovic
Journal: HemaSphere (2019)

Background: Advent of direct/non‐vitamin‐K‐dependent anticoagulants (DOAC/NOAC) has dramatically changed the practice of anticoagulation. Due to fixed dosing of direct oral anticoagulants (DOACs) and high lipophilicity, uncertainty exists about their efficacy/safety in a population of obese/overweight patients. Aims: We aimed to investigate in the real‐life setting whether DOAC anticoagulated patients with atrial fibrillation stratified according to the different BMI subgroups experience different risks of unwanted outcomes. Methods: We retrospectively investigated a real‐life cohort of 325 anticoagulated patients with atrial fibrillation who started anticoagulation in our institution in period 2011–2018. Patients received predominantly dabigatran [179/325 (55%)], followed by apixaban [74/325 (23%)] and rivaroxaban [72/325 (22%)]. Clinical data were obtained from the hospital information system. Patients were stratified according to the body mass index (BMI) subgroups: non‐obese with BMI &lt;30 kg/m 2 ; class I obesity with BMI 30–34.9 kg/m 2 ; class II+ obesity with BMI ≥35 kg/m 2 . Outcomes of interest were time to thrombosis (TTT; defined as time from inclusion to first occurrence of stroke or systemic embolism), time to bleeding [TTB; defined as time from inclusion to first occurrence of major bleeding event defined according to the International Society on Thrombosis and Haemostasis definition) and overall survival (OS; defined as time from inclusion to death of any cause). Time‐to‐event‐of‐interest curves were compared using the log‐rank test and log‐rank test for trend. Patients’ characteristics were compared using the Kruskal‐Wallis ANOVA and the χ 2 test. P values &lt;0.05 were considered to be statistically significant. The study complies with the Declaration of Helsinki and it was approved by the Institutional Review Board. Results: Among 325 analyzed patients, there were 172/325 (53%) male patients. Median age was 70 years. Three investigated BMI subgroups did not significantly differ regarding sex (P = 0.778), age (P = 0.130), estimated glomerular filtration rate (P = 0.581), predetermined stroke risk [CHA2DS2‐VASC ≥2 (P = 0.729)] or predetermined major bleeding risk [HAS‐BLED ≥3 (P = 0.519)]. Median follow‐up was 33 months. In the whole cohort of DOAC treated patients, those belonging to higher BMI subgroups were significantly more likely to experience shorter time to thrombosis (TTT, overall P = 0.083, P for trend = 0.043). This phenomenon was evident among dabigatran treated patients (TTT, overall P = 0.007, P for trend = 0.009), but not present in other DOAC subgroups. Similarly, considering whole cohort of patients, those belonging to higher BMI subgroups were significantly more likely to experience major bleeding sooner (TTB, overall P &lt; 0.001; P for trend &lt;0.001). Conversely, this phenomenon was most pronounced among patients treated with factor Xa inhibitors (TTB, overall P &lt; 0.001; P for trend &lt;0.001) but not evident in dabigatran treated patients. BMI subgroups did not differ regarding overall survival (OS, overall P = 0.470, P for trend = 0.279). Summary/Conclusion: Our findings indicate that obese patients receiving DOACs, especially ones with class II+ obesity, might be under higher risks of stroke/bleeding depending on DOAC subtype. Loss of efficacy might be associated with dabigatran, whereas higher risk of major bleeding might be associated with Xa inhibitors. Our results are limited by retrospective design, single center experience, limited number of patients and rareness of events, but deserve to be further evaluated in new and larger cohorts of patients. image