Trends in Oral Anticoagulant Choice for Acute Stroke Patients with Nonvalvular Atrial Fibrillation in Japan: The SAMURAI-NVAF Study

Abstract

BackgroundLarge clinical trials are lack of data on non‐vitamin K antagonist oral anticoagulants for acute stroke patients.AimTo evaluate the choice of oral anticoagulants at acute hospital discharge in stroke patients with nonvalvular atrial fibrillation and clarify the underlying characteristics potentially affecting that choice using the multicenter Stroke Acute Management with Urgent Risk‐factor Assessment and Improvement‐NVAF registry (ClinicalTrials.gov NCT01581502).MethodThe study included 1192 acute ischemic stroke/transient ischemic attack patients with nonvalvular atrial fibrillation (527 women, 77·7 ± 9·9 years old) between September 2011 and March 2014, during which three nonvitamin K antagonist oral anticoagulant oral anticoagulants were approved for clinical use. Oral anticoagulant choice at hospital discharge (median 23‐day stay) was assessed.ResultsWarfarin was chosen for 650 patients, dabigatran for 203, rivaroxaban for 238, and apixaban for 25. Over the three 10‐month observation periods, patients taking warfarin gradually decreased to 46·5% and those taking nonvitamin K antagonist oral anticoagulants increased to 48·0%. As compared with warfarin users, patients taking nonvitamin K antagonist oral anticoagulants included more men, were younger, more frequently had small infarcts, and had lower scores for poststroke CHADS 2, CHA 2 DS 2‐VASc, and HAS‐BLED, admission National Institutes of Health stroke scale, and discharge modified Rankin Scale. Nonvitamin K antagonist oral anticoagulants were started at a median of four‐days after stroke onset without early intracranial hemorrhage. Patients starting nonvitamin K antagonist oral anticoagulants earlier had smaller infarcts and lower scores for the admission National Institutes of Health stroke scale and the discharge modified Rankin Scale than those starting later. Choice of nonvitamin K antagonist oral anticoagulants was independently associated with 20‐day or shorter hospitalization (OR 2·46, 95% CI 1·87–3·24).ConclusionsWarfarin use at acute hospital discharge was still common in the initial years after approval of nonvitamin K antagonist oral anticoagulants, although nonvitamin K antagonist oral anticoagulant users increased gradually. The index stroke was milder and ischemia‐risk indices were lower in nonvitamin K antagonist oral anticoagulant users than in warfarin users. Early initiation of nonvitamin K antagonist oral anticoagulants seemed safe.

Early Anticoagulation for Recurrent Ischemic Stroke despite the Presence of Ventricular Bleeding

“…As advanced age is not a contraindication to the use of rivaroxaban [14], he was treated with this DOAC at the dose of 15 mg/die starting 5 days after the index event, despite the presence of intraventricular bleeding occurred after the thrombolytic therapy for the first event. Our results are even more encouraging given that randomized clinical trials with DOACs have excluded acute ischemic stroke patients, and the safety of DOAC administration soon after an index event has only been addressed by observational, prospective, and non-randomized studies [8][9][10][11][12][13]. In particular, in two prospective studies, the treatment with DOACs was commenced after a mean time of four and five days from the index event and no intracranial bleeding was observed during hospitalization [8,13], suggesting the safety of the early use of DOACs after an ischemic episode.…”

“…Our results are even more encouraging given that randomized clinical trials with DOACs have excluded acute ischemic stroke patients, and the safety of DOAC administration soon after an index event has only been addressed by observational, prospective, and non-randomized studies [8][9][10][11][12][13]. In particular, in two prospective studies, the treatment with DOACs was commenced after a mean time of four and five days from the index event and no intracranial bleeding was observed during hospitalization [8,13], suggesting the safety of the early use of DOACs after an ischemic episode. Furthermore, the early use of DOACs seems to have the best safety profile when compared with other anticoagulants [11].…”

“…However, randomized clinical trials on DOACs have systematically excluded patients with recent ischemic stroke (<7 days) in whom the risk of sHT is higher [4][5][6][7]. Despite the lack of conclusive clinical evidence, the available data from observational, longitudinal studies suggest that the early use of DOACs is safe and might reduce the risk of sHT [8][9][10][11][12][13]. Therefore, in clinical practice, these agents are perceived as safe and increasingly used even during the first days after ischemic stroke.…”

Efficacy and Safety of Dabigatran Etexilate vs. Warfarin in Asian RE-LY Patients According to Baseline Renal Function or CHADS₂ Score

“…19 The majority of non-valvular AF patients in clinical settings have normal renal function or mild impairment. 20, 21 The results of this study indicated that DE may provide a balance between the risk for ischemic stroke and the risk for bleeding in patients with decreased renal function (CrCl <50 ml/min). At the same time, it is suggested that a high dose of DE (150 mg) can be effective and may be recommended for patients with a high …”

Is Anticoagulant Therapy Unnecessary for Lower-Risk Japanese Patients With Atrial Fibrillation?

“…The neurologists often complain when they see victims of underuse or underdosing of anticoagulation. Figure 1 shows the percentages of patients with low (0), intermediate (1), and high (≥2) CHADS2 scores who were registered in the prospective, multicenter, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-NVAF Study. EDITORIAL TOYODA K of their study is the higher incidence of ischemic stroke in patients with CHADS2 score ≥2, not the low incidence in those with CHADS2 score ≤1.…”