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Triple AXEL: Rivaroxaban, warfarin confer similar safety, efficacy in AF-related stroke
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Use of rivaroxaban or warfarin initiated within 5 days of stroke onset yielded comparable safety and efficacy for prevention of early clinical stroke recurrence in patients with mild atrial fibrillation-related acute ischemic stroke.
“In this first trial to compare novel oral anticoagulants and vitamin K antagonists in patients with AF-related acute ischemic stroke, there was no difference between rivaroxaban and warfarin in the combined surrogate endpoint of new ischemic lesion or new intracranial hemorrhage on results of follow-up MRI at 4 weeks. In addition, there were no differences between the two groups in the individual components of new ischemic lesion and new intracranial hemorrhage,” researchers wrote in JAMA Neurology.
Early anticoagulation for stroke
Keun-Sik Hong, MD, from the department of neurology in Ilsan Paik Hospital at Inje University in Goyang, South Korea, and colleagues analyzed data on 195 patients who had a mild AF-related acute ischemic stroke in the previous 5 days, nonvalvular AF and were suitable for early anticoagulation. Aspirin or heparin was administered once MRI results confirmed the patient had an acute ischemic lesion.
Patients were randomly assigned to 4 weeks of rivaroxaban (n = 101; Xarelto, Janssen) or dose-adjusted warfarin (n = 94; target INR, 2.0-3.0). The rivaroxaban dose was 10 mg per day for 5 days, followed by 15 mg or 20 mg per day thereafter. Aspirin or heparin was discontinued 24 hours before treatment with rivaroxaban was initiated or when an INR of 1.7 was attained with warfarin.
MRI and other imaging tests was performed at 4 weeks to assess for new intracranial hemorrhage and ischemic lesions.
New lesions, hemorrhages
The primary endpoint was a composite of new intracranial hemorrhage or new ischemic lesion at follow-up. Secondary efficacy endpoints included length of hospitalization, new intracranial hemorrhage, major bleeding, ACS and various composites.
The modified intention-to-treat group comprised 183 patients (mean age, 70 years; 42% women) who were assessed for the primary endpoint, which occurred in 49.5% of patients assigned rivaroxaban vs. 54.5% assigned warfarin (RR = 0.91; 95% CI, 0.69-1.2). Similar findings were seen after sensitivity analyses and adjustment for factors such as age, sex and center.
New ischemic lesions were observed in 29.5% of the rivaroxaban group vs. 35.6% of the warfarin group (RR = 0.83; 95% CI, 0.54-1.26). One clinical ischemic stroke recurred in each group, which the researchers assumed to be cardioembolism.
There were no differences in the occurrence of new intracranial hemorrhages in the rivaroxaban and warfarin groups (31.6 vs. 28.7%; RR = 1.1; 95% CI, 0.7-1.71). The intracranial hemorrhages were asymptomatic hemorrhagic transformations that were close to the original ischemic lesion, according to the researchers.
In other findings, patients assigned rivaroxaban had a median hospital stay of 4 days compared with 6 days among those assigned warfarin (P < .001).
“Because this study selected patients with mild stroke severity who were considered at low risk of intracranial hemorrhage with early anticoagulation, the findings would not be applicable to those with moderate to severe stroke,” Hong and colleagues wrote.
Anticoagulation timing
The Triple AXEL trial is “interesting” in the discussion of anticoagulation timing for AF in acute ischemic stroke, Kelvin K. H. Ng, MBBS, assistant professor in stroke medicine at McMaster University in Hamilton, Ontario, Canada, and William Whiteley, BMBCh, MRC clinician scientist and honorary consultant neurologist at the Centre for Clinical Brain Sciences at the University of Edinburgh in Scotland, wrote in a related editorial.
“Early anticoagulation with a direct oral anticoagulant and warfarin in patients with mild stroke is feasible, but whether this is of benefit to all patients with acute stroke and AF has yet to be demonstrated,” Ng and Whiteley wrote.
The editorial authors also noted that early vs. late direct oral anticoagulation is under investigation in “at least” three randomized trials, including ELAN, START and Timing of Oral Anticoagulant Therapy in Acute Ischemic Stroke with Atrial Fibrillation. – by Darlene Dobkowski
Disclosures: Hong reports he received grants from Bayer, Bayer Korea Ltd, Boehringer Ingelheim, Boehringer Ingelheim Korea, Ostuka Korea and Pfizer Korea and personal fees from Bayer Korea, Boehringer Ingelheim Korea, Chong Kun Dang Pharm, Daichi Sankyo Korea, Dong Wha Pharm, Pfizer Korea, Sanofi Korea and United Pharm. Nh and Whiteley report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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