Direct oral anticoagulant (DOAC) use is steadily increasing as it offers effective prevention of cardioembolic stroke and venous thromboembolism.^{Reference Alam, Khan and Fatima1} It is estimated that approximately 20% of patients presenting with ischemic stroke are on DOACs and are therefore often excluded from receiving intravenous thrombolysis (IVT), even if they present within the therapeutic time window.^{Reference Bang, Park and Jeong2} This results in a significant proportion of patients being denied a potentially beneficial therapy. Importantly, recent evidence from large observational studies suggests that IVT in selected patients with recent DOAC use is not associated with an increased risk of intracranial hemorrhage (ICH).^{Reference Meinel, Wilson and Gensicke3,Reference Bücke, Jung and Kaesmacher4} The recent target trial analysis by Meinel et al. confirms prior observational data on the safety of off-label thrombolysis in recent DOAC use as it showed that recent DOAC use did not increase the risk of symptomatic ICH and patients who received IVT had better clinical outcomes after stroke.^{Reference Meinel, Bücke and D’Anna5} A recent meta-analysis reported that patients with acute ischemic stroke who received IVT while on DOAC therapy had similar rates of hemorrhagic complications and functional independence compared to those not on DOACs.^{Reference Ghannam, Almajali and Galecio-Castillo6} Despite this, the Canadian Stroke Best Practice Recommendations advise against the use of IVT in patients who have ingested DOACs within the past 48 hours.^{Reference Heran, Lindsay and Gubitz7} These recommendations are based primarily on the pharmacokinetics of DOACs, specifically their 12–15-hour half-life, and the theoretical risk of hemorrhagic complications, rather than data from randomized controlled trials.^{Reference Alam, Khan and Fatima1}

In this study, we aimed to assess real-world clinical practice and identify barriers to thrombolysis decision-making in the context of DOAC-associated ischemic stroke. To achieve this, we conducted a survey across 13 stroke centers in Canada, focusing on access and turnaround time for laboratory testing for DOAC levels, institutional practices for treating these patients with recent DOAC ingestion and lastly, availability and use of reversal agents in the setting of acute ischemic stroke, since understanding this variability is critical for informing future clinical guidance and research in this high-risk and growing patient population.

In the current study, we conducted an invite-only online survey via Microsoft Forms among established clinician scientists in stroke across 13 Canadian stroke centers (Table 1), representing the majority of provinces in Canada. Participating centers were identified through the Canadian Stroke Consortium based on their leadership in hyperacute stroke research and prior experience in multicenter clinical trials, representing major academic stroke centers and research-active stroke programs across multiple Canadian provinces. This was an invite-only survey, with one response per site. Collectively, the 13 centers represented 6 provinces across Canada and included 11 comprehensive stroke centers and 2 primary stroke centers. To preserve brevity, institutional patient volumes were not collected; however, all comprehensive centers function as tertiary or quaternary referral hubs for regional stroke care. The survey and its procedures were reviewed by the institutional Research Ethics Board and were deemed exempt from formal ethics review, as the project involved a voluntary, anonymized survey of healthcare professionals and did not include patient data.

Table 1. List of Canadian stroke centers and the respondents participating in this study

The aim of the study was to examine the routine clinical practice and barriers to administering IVT in patients who have recently taken DOAC within 48 hours before stroke. The survey was designed to capture real-world data about access and turnaround time for DOAC level testing, any specific institutional protocols for use of IVT for patients on DOAC, challenges to thrombolysis and reversal decision-making, availability and use of DOAC reversal agents such as idarucizumab and andexanet alfa in the setting of ischemic stroke and optional free text for qualitative data. The survey is available as Supplemental Material 1.

Participation in the survey was voluntary and anonymous, and responses were de-identified. Descriptive statistics were used to present the access to DOAC level testing along with reported use and availability of reversal agents. Categorical variables were reported as frequencies and percentages. Open-ended responses were reviewed to identify common concerns or variations in clinical reasoning. 95% confidence intervals for proportions were calculated using the Clopper–Pearson binomial method in R (version 4.4.1; Foundation for Statistical Computing, Vienna, Austria).

There was no formal hypothesis formulated given the exploratory aim of the study. This cross-sectional survey was conducted between February 1 and 24, 2025. Invitations were emailed to 13 stroke neurologists or site leads identified through the Canadian Stroke Consortium network, based on their leadership in hyperacute stroke research and previous participation in multicenter trials. Each center provided a single institutional response to avoid duplication. All invited participants completed the survey (100% response rate among invitees). Twelve respondents were stroke neurologists, and one was a general neurologist. The survey instrument was piloted and refined for clarity and face validity prior to distribution and is available in Supplementary Material 1.

Among the participating centers, 9/13 (69%) reported onsite availability of DOAC level testing, 2/13 (15%) had access to an external laboratory and 2/13 (15%) were not sure about its availability for assessing anticoagulant activity in DOAC-treated patients (Figure 1A). The centers with availability to assess DOAC levels indicated different turnaround times for getting the results, as 5/13 (38%) reported the turnaround time to be more than 60 minutes, 3/13 (23%) reported this to be 30–60 minutes, 1/13 (7%) indicated 15–30 minutes and 2/13 (15%) indicated that it was less than 15 minutes (Figure 1B).

Figure 1. Availability and turnaround time of direct oral anticoagulant (DOAC) level testing. The figure illustrates the proportion of centers with access to Factor Xa level testing (A) and the reported usual turnaround time (B). Data are presented as counts and percentages of total survey respondents.

In terms of institutional approaches to manage ischemic stroke patients who are receiving DOAC, 9/13 centers (69%) reported that DOAC level testing was not used in thrombolysis decision-making in DOAC-associated ischemic stroke, 2/13 centers (15%) indicated regular use of DOAC level testing who were the same participants with turnaround time less than 15 minutes and 2/13 centers (15%) reported that the use of DOAC level testing or decision-making depends on the clinical scenario of patients (Figure 2).

Figure 2. Use of direct oral anticoagulant (DOAC) levels testing to guide thrombolysis decisions in acute ischemic stroke patients who are taking DOAC. The figure summarizes participants’ reports regarding considering Factor Xa level testing result into thrombolysis decision-making. Data are presented as counts and percentages of total survey respondents.

Among the nine centers that did not routinely use DOAC level testing to guide thrombolysis, the most frequently reported barrier was a lack of clear guidelines (8/9 centers, 88%), followed by prolonged turnaround time (6/9 centers, 66%) and unavailability of testing (2/9 centers, 22%). When expressed relative to all participating centers, these barriers corresponded to 8/13 centers (61%), 6/13 centers (46%) and 2/13 centers (15%), respectively. In addition, 1 of 13 centers (7%) reported that the result of the test would not change treatment decision due to potential future randomization of the ACT GLOBAL (A Multi-faCtorial, mulTi-arm, Multi-staGe, Randomised, gLOBal Adaptive pLatform Trial for Stroke). One of 13 centers (7%) indicated a lack of knowledge to guide the treatment approach, and 1/13 center (7%) indicated concerns about justifying the use of a potentially prothrombotic reversal agent to enable thrombolysis, particularly given observational data suggesting the safety of thrombolysis in patients on DOACs. Barriers and their frequency are summarized in Figure 3.

Figure 3. Reported barriers to using direct oral anticoagulant (DOAC) level testing for guiding thrombolysis decisions in DOAC-treated ischemic stroke patients. The figure summarizes the barriers pointed out by the respondents to routinely using DOAC level results in thrombolysis decision-making. Data are presented as counts and percentages of the total number of respondents.

Among these centers, 9/13 (69%) had ready access to idarucizumab, a dabigatran reversal agent, 3/13 (23%) had access with special approval/orders and 1/13 (7%) had no access (Figure 4A). In the recent two years, 8/13 centers (61%) never used idarucizumab, and 5/13 centers (38%) reported using it 1–5 times for acute ischemic stroke patients (Figure 4B).

Figure 4. Availability and use of idarucizumab as a reversal agent for dabigatran and andexanet alfa for reversing the effects of factor Xa inhibitors. The figure summarizes the participants reporting availability of idarucizumab (A) and its use for acute ischemic stroke patients undergoing thrombolysis within the past two years (B), as well as the availability of andexanet alfa (C) and its use or acute ischemic stroke patients undergoing thrombolysis within the past two years (D).

Based on our survey study, access to andexanet alfa, a Factor Xa inhibitor reversal agent, was more limited across the participating Canadian centers compared to idarucizumab. Within these centers, 9/13 (69%) indicated that andexanet alfa was not available, 3/13 (23%) required special approval/orders and only 1/13 (7%) had ready access to andexanet alfa (Figure 4C). In the past two years, 12/13 centers (92%) never used andexanet alfa, and only 1/13 center (7%) used it 1–5 times (Figure 4D). A comprehensive summary of all survey responses, including absolute counts, percentages and 95% confidence intervals for each item, is provided in Supplementary Material 2.

The current survey across 13 Canadian stroke centers demonstrates significant variability in the current practice in using IVT for acute ischemic stroke patients who have taken DOAC within the last 48 hours. Our findings reveal that there is no harmonized approach across different centers, and there is a large variance in access to reversal agents and use of DOAC level testing. This lack of a standardized approach highlights an important gap in the acute stroke care for the growing patient populations using DOAC treatment, as previously reported.^{Reference Kristoffersen, Seiffge and Meinel8} In fact, the majority of the participants do not use DOAC level testing to guide their IVT decision in ischemic stroke patients on DOAC therapy, perhaps due to either a lack of available and/or timely testing or the absence of a clear recommendation for performing and interpreting these tests. There were various multifactorial barriers associated with complicated decision-making including limited availability of DOAC level testing, prolonged turnaround time and, more importantly, the absence of clear guidelines. These barriers emphasize infrastructural and clinical uncertainty.

Our survey findings indicate that, in the absence of reliable evidence, variations in practice persist, and it is further influenced by local resources and different interpretations of the limited available data. Given that approximately 20% of patients with ischemic stroke are taking DOAC, the lack of a solid evidence-based approach would contribute to missed treatment opportunities.^{Reference Bang, Park and Jeong2}

To address this issue, the Canada-led international multicenter randomized trial (DOSE subdomain of ACT GLOBAL trial, NCT06352632) is well-designed to address the knowledge gap by assessing the safety and efficacy of a lower dose of tenecteplase (0.18 mg/kg body weight) and standard dose of tenecteplase (0.25 mg/kg body weight) in patients being treated with DOAC. The DOAC Intravenous Thrombolysis Trial (NCT# NCT06571149) is another Swiss-led trial that is testing the safety and efficacy of standard dose IVT in DOAC-treated patients. Both trials do not require DOAC level measurements prior to enrollment. Results from these trials could standardize national guidelines and improve time-sensitive IVT therapy for patients who are taking DOAC. Together, these findings point to important policy implications and suggest that clinical trials and guideline development may help reduce unwarranted variation in practice and promote more consistent, evidence-based care.

This study should be interpreted in light of certain limitations. This invite-only survey sampled major academic stroke centers and therefore may not reflect the full spectrum of frontline practice across Canadian hospitals. As a result, access to DOAC level testing and reversal agents may be overestimated, while barriers to thrombolysis decision-making may be underestimated in primary or rural settings. Nevertheless, characterizing practice patterns and perceived barriers in these centers remains important, as they frequently inform guideline development, participate in clinical trials and serve as early adopters of emerging evidence.