Despite concerns about the potential bleeding risk, IV thrombolysis could be safely given to ischemic stroke patients within a day of direct oral anticoagulant (DOAC) therapy, according to observational data from Japan.
Between DOAC users and peers not taking oral anticoagulants within 48 hours of stroke onset, rates of symptomatic intracranial hemorrhage, accompanied by a ≥4-point increase on the NIH Stroke Scale score from baseline, were a comparable 2.5% and 2.4%, respectively, after alteplase (tPA) administration, based on a single-center prospective Japanese registry.
There were also no significant differences in intracranial hemorrhage within 36 hours or mortality at 3 months.
Notably, Japan-approved alteplase at a lower dose of 0.6 mg/kg, and the country’s guidelines permit IV thrombolysis at least 4 hours after most recent DOAC dose in select patients, according to Masatoshi Koga, MD, PhD, of the National Cerebral and Cardiovascular Center in Oasaka, and colleagues in the Journal of the American Heart Association.
Koga’s group cautioned that the results may not be extrapolated to other countries using alteplase at 0.9 mg/kg, and that the Japanese decide on IV thrombolysis for people on anticoagulants based on nonspecific coagulation assays, not necessarily blood concentrations of DOACs.
Even so, similar findings have been reported in a recent analysis of DOAC users in the U.S. “Get With the Guidelines-Stroke” registry.
“Most societal guidelines recommend against the use of intravenous alteplase in patients who have taken a DOAC within the preceding 48 hours, owing to the perceived increased risk of hemorrhage, though the evidence for this has never been firmly established,” commented Wayneho Kam, MD, of Duke University Medical Center in Durham, North Carolina, and Ying Xian, MD, PhD, of University of Texas Southwestern Medical Center in Dallas.
“Based on these findings, it appears safe to administer low-dose alteplase to selected patients who had taken DOACs within 24 hours before stroke onset,” Kam and Xian wrote in an accompanying editorial. “Given the established benefit and relatively low risk of harm associated with low-dose alteplase, future guidelines may consider omitting recent use of DOACs within 48 hours as an absolute contraindication to intravenous alteplase for patients with acute ischemic stroke.”
The Japanese registry covered consecutive patients with acute ischemic stroke presenting at one center from 2011 to 2021. These were stroke patients admitted 7 days from symptom onset or the last known well time.
Of the 793 eligible individuals who received IV thrombolysis, 753 had not taken any oral anticoagulants, whereas 40 patients had taken DOACs — dabigatran (Pradaxa, n=6), rivaroxaban (Xarelto, n=8), apixaban (Eliquis, n=16), and edoxaban (Lixiana, n=10) — within 24 hours of stroke onset. There were no patients with last DOAC intake 24-48 hours in the study.
DOAC users were older (ages 80 vs 76); presented with higher baseline NIH Stroke Scale scores (15 vs 9); and more frequently had atrial fibrillation (90.0% vs 31.3%), congestive heart failure (22.5% vs 9.7%), and prior strokes (47.8% vs 16.1%).
Ultimately, however, this group still had no more major hemorrhagic events (2.5% vs 1.1%) or mortality at 3 months (5.0% vs 5.7%, respectively) than DOAC nonusers, according to Koga and colleagues. They also reported that the two groups shared similarly favorable outcomes at 3 months (modified Rankin Scale score 0-2: 59.4% vs 58.2%, P=0.46).
“Therefore, it could be argued that the odds of symptomatic intracranial hemorrhage would be even lower and the odds of favorable outcomes would be even higher in the DOAC group if further adjustments could be made,” Kam and Xian suggested.
“Although this study did not provide a definite answer to the safety of intravenous alteplase for patients with ischemic stroke with recent use of DOACs, its findings partially affirm the recommendations set forth by the Japan Stroke Society,” they said.
Koga and colleagues acknowledged that the results of their small and single-center study should be confirmed in larger, prospective studies.
Disclosures
The study was funded by a Japan Agency for Medical Research and Development grant.
Koga disclosed relationships with Daiichi Sankyo and support from Takeda, Daiichi-Sankyo, Nippon Boehringer Ingelheim, and Shionogi. Co-authors disclosed relationships with, and/or support from, Takeda Pharmaceutical, Nippon, Boehringer Ingelheim, Daiichi Sankyo, Eisai, Panasonic, GE Precision Healthcare, Bristol Myers Squibb, Shimadzu, Bayer Yakuhin, Otsuka, Novartis, and Abbott Medical.
Xian disclosed support from the American Heart Association and Genentech and a relationship with Boehringer Ingelheim. Kam disclosed no relationships with industry.
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