Association Between Low-Dose Rivaroxaban With or Without Aspirin and Ischemic Stroke Subtypes

Abstract

IMPORTANCE The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) randomized clinical trial was stopped early owing to the efficacy of low-dose rivaroxaban plus aspirin in preventing major cardiovascular events. The main reason for early trial termination was the effect of combination therapy on reducing ischemic strokes. OBJECTIVE To analyze the association between low-dose rivaroxaban with or without aspirin and different ischemic stroke subtypes. DESIGN, SETTING, AND PARTICIPANTS This is a secondary analysis of a multicenter, double-blind, randomized, placebo-controlled study that was performed in 33 countries from March 12, 2013, to May 10, 2016. Patients with stable atherosclerotic vascular disease were eligible, and a total of 27 395 participants were randomized and followed up to February 6, 2017. All first ischemic strokes and uncertain strokes that occurred by this date were adjudicated using TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. The analysis of ischemic stroke subtypes was evaluated using an intention-to-treat principle. Statistical analysis was performed from March 12, 2013, to February 6, 2017. INTERVENTIONS Participants received rivaroxaban (2.5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban (5 mg twice a day), or aspirin (100 mg once a day). MAIN OUTCOMES AND MEASURES Risk of ischemic stroke subtypes during follow-up. RESULTS A total of 291 patients (66 women; mean [SD] age, 69.4 [8.5] years; 43 [14.8%] had a previous nonlacunar stroke) experienced an ischemic stroke. During the study, 49 patients (16.8%) received a diagnosis of atrial fibrillation. Applying TOAST criteria, 59 strokes (20.3%) were cardioembolic, 54 strokes (18.6%) were secondary to greater than 50% stenosis of the ipsilateral internal carotid artery, 42 strokes (14.4%) had a negative evaluation that met criteria for embolic stroke of undetermined source, and 21 strokes (7.2%) were secondary to small vessel disease. There were significantly fewer cardioembolic strokes (hazard ratio [HR], 0.40 [95% CI, 0.20-0.78]; P = .005) and embolic strokes of undetermined source (HR, 0.30 [95% CI, 0.12-0.74]; P = .006) in the combination therapy group compared with the aspirin-only group. A trend for reduction in strokes secondary to small vessel disease (HR, 0.36 [95% CI, 0.12-1.14]; P = .07) was not statistically significant. No significant difference was observed between the 2 groups in strokes secondary to greater than 50% carotid artery stenosis (HR, 0.85 [95% CI, 0.45-1.60]; P = .61). Rivaroxaban, 5 mg, twice daily showed a trend for reducing cardioembolic strokes compared with aspirin (HR, 0.57 [95% CI, 0.31-1.03]; P = .06) but was not associated with reducing other stroke subtypes. CONCLUSIONS AND RELEVANCE For patients with systemic atherosclerosis, low-dose rivaroxaban plus aspirin was associated with large, significant reductions in cardioembolic strokes and embolic strokes of undetermined source. However, these results of exploratory analysis need to be independently co...

Regional, sex, and age differences in diagnostic testing among participants in the NAVIGATE-ESUS trial

“…A recent secondary analysis of the Cardiovascular OutComes for People using Anticoagulation StrategieS (COMPASS) trial found that among patients with systemic atherosclerosis, low-dose rivaroxaban-plus-aspirin was associated with significant reductions in ESUS. 20 In view of the fact that two large, recent randomized trials failed to demonstrate the superiority of anticoagulants over aspirin in patients with ESUS, our findings support a strategy of extending the diagnosis evaluation of patients with ESUS, in an attempt to more precisely categorize the cause of the stroke and to individualize secondary prevention.…”

Inconsistent centralised versus non-centralised ischaemic stroke aetiology

“… 9–11 There are several aetiological subtyping systems 12–19 ; however, despite the limited discriminatory ability and prognostic value, 8 the Trial of Org 10 172 in Acute Stroke Treatment (TOAST) system 12 remains the most widely used aetiological categorising system in clinical research and practice. 20 21 …”

Vergangenheit und Zukunft des ESUS-Konzepts

“…In der COMPASS-Studie, die Patienten mit koronarer Herzerkrankung oder peripher-arterieller Verschlusskrankheit einschloss [23] gab es eine Untergruppe von Patienten, die einen Schlaganfall erlitten [24]. Die Patienten wurden dahingehend analysiert, welche Ätiologie des Schlaganfalls nach den TOAST-Kriterien vorlag.…”