Recurrent Stroke With Rivaroxaban Compared With Aspirin According to Predictors of Atrial Fibrillation

Abstract

IMPORTANCE The NAVIGATE ESUS randomized clinical trial found that 15 mg of rivaroxaban per day does not reduce stroke compared with aspirin in patients with embolic stroke of undetermined source (ESUS); however, it substantially reduces stroke risk in patients with atrial fibrillation (AF).OBJECTIVE To analyze whether rivaroxaban is associated with a reduction of recurrent stroke among patients with ESUS who have an increased risk of AF. DESIGN, SETTING, AND PARTICIPANTS Participants were stratified by predictors of AF, including left atrial diameter, frequency of premature atrial contractions, and HAVOC score, a validated scheme using clinical features. Treatment interactions with these predictors were assessed. Participants were enrolled between December 2014 and September 2017, and analysis began March 2018. INTERVENTION Rivaroxaban treatment vs aspirin. MAIN OUTCOMES AND MEASURES Risk of ischemic stroke.RESULTS Among 7112 patients with a mean (SD) age of 67 (9.8) years, the mean (SD) HAVOC score was 2.6 (1.8), the mean (SD) left atrial diameter was 3.8 (1.4) cm (n = 4022), and the median (interquartile range) daily frequency of premature atrial contractions was 48 (13-222). Detection of AF during follow-up increased for each tertile of HAVOC score: 2.3% (score, 0-2), 3.0% (score, 3), and 5.8% (score, >3); however, neither tertiles of the HAVOC score nor premature atrial contractions frequency impacted the association of rivaroxaban with recurrent ischemic stroke (P for interaction = .67 and .96, respectively). Atrial fibrillation annual incidence increased for each tertile of left atrial diameter (2.0%, 3.6%, and 5.2%) and for each tertile of premature atrial contractions frequency (1.3%, 2.9%, and 7.0%). Among the predefined subgroup of patients with a left atrial diameter of more than 4.6 cm (9% of overall population), the risk of ischemic stroke was lower among the rivaroxaban group (1.7% per year) compared with the aspirin group (6.5% per year) (hazard ratio, 0.26; 95% CI, 0.07-0.94; P for interaction = .02). CONCLUSIONS AND RELEVANCEThe HAVOC score, left atrial diameter, and premature atrial contraction frequency predicted subsequent clinical AF. Rivaroxaban was associated with a reduced risk of recurrent stroke among patients with ESUS and moderate or severe left atrial enlargement; however, this needs to be independently confirmed before influencing clinical practice.

Left Atrial Volume Index Predicts New-Onset Atrial Fibrillation and Stroke Recurrence in Patients with Embolic Stroke of Undetermined Source

“…Historically, the most commonly used measurement of LA size is the linear anterioposterior dimension due to its ease of use. Exploratory subgroup analyses of NAVIGATE ESUS found that rivaroxaban reduced the risk of ischemic stroke in patients with LAD >4.6 cm, and LAD was associated with higher risk of AF [8], but not recurrent stroke [9]. Recent trials such as the ARCADIA trial investigates the use of anticoagulation in ESUS patients at high risk of atrial cardiopathy, adopting a LADi cutoff of ≥3 cm/m 2 as a marker of left atrial enlargement [10].…”

Atrial Cardiopathy and Likely Pathogenic Patent Foramen Ovale in Embolic Stroke of Undetermined Source

“…22 In addition, ongoing research aims to assess the optimal antithrombotic treatment in patients with ESUS and atrial cardiopathy. [23][24][25][26] With regard to PFO, although it is now clear that percutaneous closure of PFO reduces the risk of stroke recurrence in patients younger than 60 years of age, there are many other questions still open, like whether percutaneous PFO closure is beneficial in older patients, and whether the echocardiographic characteristics of the PFO (e.g., the size of the shunt and the presence of atrial septal aneurysm) and the clinical characteristics of the patient (e.g., the RoPE score) could identify a subpopulation which may benefit by percutaneous PFO closure beyond current recommendations. 8,9,[27][28][29] Ongoing and future research will hopefully address many of these open questions and facilitate the improvement of outcomes in this population.…”

Vergangenheit und Zukunft des ESUS-Konzepts

“…In der NAVIGATE-ESUS-Studie wurde bei 4022 Teilnehmen der Durchmesser des linken Vorhofs in der Echokardiographie gemessen [16]. Der mittlere Durchmesser betrug 3,8 cm.…”