Intravenous Thrombolysis in Patients on Direct Oral Anticoagulants: Analysis of the Get With The Guidelines Stroke Registry

Abstract

Background

Intravenous thrombolysis for acute ischemic stroke (AIS) is a proven effective treatment. Whether thrombolysis in patients with AIS with recent direct oral anticoagulant (DOAC) use is safe and efficacious is not well established. We aimed to compare outcomes of patients with AIS and recent DOAC use who received thrombolysis to those otherwise eligible but excluded due to recent DOAC use.

Methods

This study included patients for the GWTG (Get With The Guidelines) registry with a diagnosis of AIS within 4.5 hours from last known normal, on a DOAC, and either (1) received intravenous thrombolysis, or (2) were excluded from thrombolysis with coagulopathy being the only reason for exclusion. We used univariate and adjusted binary logistic regression models with clustering by site to compare the 2 groups’ functional status (ambulation on discharge and discharge disposition) and reported rates of safety outcomes in the thrombolysis group.

Results

The study sample included 48 907 patients with AIS using a DOAC; 4702 received thrombolysis and 44 205 did not. In adjusted logistic regression models, patients with recent DOAC use receiving thrombolysis had increased odds of independent ambulation at discharge (odds ratio [OR], 1.35[ 95% CI, 1.21–1.50]) and home discharge (OR, 1.33 [95% CI, 1.22–1.46]). The rate of symptomatic intracranial hemorrhage with intravenous thrombolysis in patients with recent DOAC use was 3.5% (95% CI, 3.0%–4.1%).

Conclusions

In this study, intravenous thrombolysis was associated with improved functional outcomes in patients with recent DOAC use and appeared safe. Given the study limitations, findings require validation by prospective trials.

Nonstandard Abbreviations and Acronyms

DOAC

direct oral anticoagulant

GWTG

Get With The Guidelines

IPTW

inverse probability of treatment weighting

NIHSS

National Institutes of Health Stroke Scale

Clinical Perspective.

What Is New?

• This study suggests that intravenous thrombolysis may be safe and effective in patients with ischemic stroke with recent ingestion of a direct oral anticoagulant

What Are the Clinical Implications?

• This study supports a randomized controlled trial testing and efficacy and safety of intravenous thrombolysis in patients with ischemic stroke with recent ingestion of a direct oral anticoagulant

Stroke is a leading cause of death and disability. ¹ Intravenous thrombolysis for acute ischemic stroke is a robustly effective treatment, leading to a reduction in disability among 1 out of 3 patients treated. ² Intravenous thrombolysis is the standard of care for patients with acute ischemic stroke presenting within 4.5 hours. An important and common reason for exclusion from acute stroke thrombolysis is the use of anticoagulant medications within 48 hours before stroke. Direct oral anticoagulant (DOAC) use within 48 hours before presentation is an exclusion criterion for intravenous thrombolysis per the recent American Heart Association/American Stroke Association Guidelines. ³ This is largely due to the lack of data regarding safety of thrombolysis among patients with a recent DOAC ingestion. Consequently, clinical practice of thrombolysis among these patients is quite heterogenous. Although some clinicians treat patients on DOACs with thrombolysis based on features such as drug level, factor Xa level, or time within 48 hours since last ingestion, many clinicians consider DOAC use within 48 hours as an absolute exclusion to thrombolysis. ⁴ In Europe, where dabigatran is a commonly prescribed DOAC, the use of idarucizumab as a reversal agent followed immediately by alteplase has been described. ⁵

DOACs are the most commonly used anticoagulant medications and their use before stroke has been estimated to results in the exclusion of an estimated 20% to 30% of otherwise eligible patients from receiving intravenous thrombolysis. ⁶ Importantly, DOAC use is expected to increase among patients with incident or recurrent strokes with its expanding indications for patients with atrial fibrillation, ⁷ , ⁸ cardiovascular prevention, ⁹ and venous thromboembolism ¹⁰ as well as the increasing incidence of atrial fibrillation over time with the aging population.

In this study, we aimed to compare outcomes of patients with acute ischemic stroke with recent DOAC use and received thrombolysis to those would have been otherwise eligible but were not treated solely due to recent DOAC use.

METHODS

Regulatory Aspects and Data Sharing

The Lifespan Institutional Review Board waived this study as it is an analysis of deidentified data. Data from GWTG (Get With The Guidelines) are available upon approval of a submitted proposal to the American Heart Association. Each participating hospital received either human research approval to enroll cases without individual patient consent under the common rule, or a waiver of authorization and exemption from subsequent review by their institutional review board. Advarra, the institutional review board for the American Heart Association, determined that this study is exempt from institutional review board oversight.

Inclusion and Exclusion

This study used data from patients with acute ischemic stroke entered by individual sites into GWTG registry between November 13, 2014 until December 31, 2022. We included patients (1) with a diagnosis of acute ischemic stroke; (2) who presented to an acute care facility within 4.5 hours from last known normal; (3) who had recent use of DOAC; and (4) who either received intravenous thrombolysis or were excluded from thrombolysis with DOAC‐related coagulopathy being the only reason for exclusion listed.

We excluded patients who (1) were transferred to another acute care facility; (2) received thrombolysis at an outside facility; (3) had discharge destination missing or unable to determine; (4) experienced stroke in the hospital; and (5) had missing data on any major contraindication.

In the GWTG registry, recent use of DOAC was defined as within 7 days from hospital arrival. Although the exact date and time of last DOAC use were not available, a prior study from GWTG registry that linked GWTG patients with the ARAMIS Addressing Real‐World Anticoagulant Management Issues in Stroke) registry found that 53% of patients recorded as recent DOAC use in GWTG had recorded DOAC ingestion within 48 hours of hospital arrival. ¹¹ Furthermore, this study did not show differences in symptomatic intracranial hemorrhage rates between within 48 hours and beyond 48 hours treated patients. ¹¹

Covariates

We included the following covariates:

1. Demographic variables: age, biological sex, race (White, Black, Asian), ethnicity (Hispanic versus Non‐Hispanic), and arrival method (by emergency medical services versus others)

2. Medical history: atrial fibrillation, prosthetic heart valve, coronary artery disease or prior myocardial infarction, carotid stenosis, diabetes, peripheral vascular disease, hypertension, smoking, hyperlipidemia, heart failure, stroke, and chronic kidney disease.

3. Clinical variables: body mass index, National Institutes of Health Stroke Scale (NIHSS) score, systolic and diastolic blood pressure on arrival.

4. Laboratory and imaging variables: international normalized ratio (INR)

5. In‐hospital treatment: acute endovascular treatment

Outcomes

The primary outcomes were ambulatory status at discharge and discharge disposition. Good outcomes were considered as independent ambulation at discharge and discharge to home (versus other dispositions). The safety outcomes were symptomatic intracranial hemorrhage, serious systemic hemorrhage, and in‐hospital death or discharge to hospice. Symptomatic intracranial hemorrhage was defined using the GWTG definition that relies on the National Institute of Neurological Disorders and Stroke tissue plasminogen activator trials criteria, ¹² that is, presence of hemorrhage documented by computed tomography or magnetic resonance imaging and a physician’s note indicating clinical deterioration due to the hemorrhage. Serious systemic hemorrhage was defined as bleeding <36 hours from intravenous thrombolysis (not including symptomatic intracranial hemorrhage) and >3 U of packed red blood cell transfusion <7 days or before discharge (whichever was earlier), with a physician note attributing the bleeding problem as the reason for the transfusion.

Statistical Analysis

The American Heart Association Precision Medicine Platform (https://precision.heart.org) was used for data analysis. We compared 2 patient groups: those receiving intravenous thrombolysis and those excluded due to recent DOAC use. We compared the covariates between the 2 groups. We then calculated the safety outcome rates in patients receiving intravenous thrombolysis and used binary regression models including age and NIHSS score and other variables achieving statistical significance in univariate analyses to determine factors associated with symptomatic intracranial hemorrhage. We built binary logistic regression models to determine the association between intravenous thrombolysis and the primary outcomes, both unadjusted and adjusted for age, sex, White race, Black race, Asian race, Hispanic ethnicity, NIHSS score, atrial fibrillation, hypertension, coronary artery disease or prior myocardial infarction, carotid stenosis, diabetes, smoking, hyperlipidemia, history of stroke, arrival by emergency medical services, and acute endovascular treatment. In sensitivity analyses, we determined associations between intravenous thrombolysis and study outcomes across NIHSS score strata (0–5, 6–10, 11–15, and >15) and excluding patients who were not ambulating independently before the index ischemic stroke. We also performed interaction analyses to compare the rates of primary outcomes between the 2 groups stratified by NIHSS score <5 and NIHSS score ≥5 and by whether endovascular treatment was performed. Finally, to improve the robustness of our methodology and reduce bias, we performed additional analyses with inverse probability of treatment weighting and adjusting for age and NIHSS score as well as weighting and adjusting for age, NIHSS score, ambulatory status before admission, admission year, annual intravenous thrombolysis volume, sex, atrial fibrillation, diabetes, peripheral vascular disease, hyperlipidemia, heart failure, and INR. We accounted for within‐hospital clustering by fitting population‐averaged logistic models using generalized estimating equations, hospital‐level clustering, and robust SEs. Data were analyzed using Python and P<0.05 was considered significant. Missing data were not imputed.

RESULTS

We identified 128 758 patients with acute ischemic stroke who arrived at an acute health care facility within 4.5 hours from last known normal and had used a DOAC within the past 7 days. After applying the exclusion criteria in the Figure 1, the final sample included 48 907 patients; 4702 received thrombolysis and 44 205 did not. The mean age was 75.1 and 50.5% were men. The number of patients with absolute and relative contraindications for thrombolysis based on definitions used in the GWTG registry are shown in Table S1.

Figure 1. Patient flow chart.

GWTG‐Stroke indicates Get With The Guidelines‐Stroke.

Baseline Patient and Hospital Characteristics

A comparison of covariates across the 2 groups is shown in Table 1. It is noteworthy that patients who received thrombolysis were younger (median age,74 [interquartile range, 64–83] versus 77 [interquartile range, 68–85], P<0.001), had higher rates of arrival by emergency medical services (79% versus 69.8%, P<0.001), had higher median NIHSS score (9 [interquartile range, 5–16] versus 5 [interquartile range, 2–13], P<0.001), and had higher rates of receipt of endovascular treatment (19.9% versus 15.8%, P<0.001). Other variables are listed in Tables 1 and 2.

Table 1.

Baseline Characteristics of Patients With Versus Without Thrombolytic Therapy

	Missing	No thrombolysis (44 205)	Thrombolysis (4702)	P value
Age, y	0	77 (68–85)	74 (64–83)	<0.001
Male sex	12	50.2% (22180)	53.7% (2522)	<0.001
White race	7	79.0% (34921)	72.8% (3422)	<0.001
Black race	7	13.0% (5735)	16.1% (755)	<0.001
Asian race	7	2.5% (1083)	3.7% (173)	<0.001
Other race*	7	0.6% (252)	0.8% (37)	0.081
Hispanic ethnicity	7	6.3% (2805)	9.9% (467)	<0.001
Arrive by emergency medical services	11	69.8% (30835)	79.0% (3714)	<0.001
Atrial fibrillation	91	73.8% (32575)	70.1% (3289)	<0.001
Prosthetic heart valve	91	2.3% (1005)	1.1% (53)	<0.001
Coronary artery disease/prior myocardial infarction	91	32.3% (14234)	28.5% (1339)	<0.001
Carotid stenosis	91	5.0% (2186)	2.7% (126)	<0.001
Diabetes	91	34.7% (15306)	33.0% (1547)	0.019
Peripheral vascular disease	91	6.5% (2872)	3.8% (176)	<0.001
Hypertension	91	81.8% (36101)	79.7% (3741)	<0.001
Smoker	91	9.9% (4349)	12.4% (582)	<0.001
Hyperlipidemia	91	59.1% (26096)	51.3% (2407)	<0.001
Heart failure	91	21.7% (9569)	20.0% (938)	0.008
History of stroke	90	38.4% (16988)	28.9% (1357)	<0.001
Chronic kidney disease	91	14.4% (6340)	9.1% (427)	<0.001
Body mass index in kg/m2	12 810	27.8 (24.2–32.4)	28.2 (24.5–33.0)	<0.001
National Institutes of Health Stroke Scale score	671	5 (2–13)	9 (5–16)	<0.001
Systolic BP in mm Hg	11 083	150 (132–171)	153 (136–172)	<0.001
Diastolic BP in mm Hg	11 122	83 (72–95)	87 (75–99)	<0.001
International normalized ratio	15 468	1.2 (1.1–1.4)	1.1 (1.0–1.2)	<0.001
Endovascular treatment	0	15.8% (7004)	19.9% (934)	<0.001

BP indicates blood pressure.

^*Other indicates non‐White, non‐Black, and non‐Asian.

Table 2.

Hospital Characteristics Stratified Based on Thrombolysis Versus No Thrombolysis

	Missing	No thrombolysis (44 205)	Thrombolysis (4702)	P value
Hospital bed number	4600
0–74		2.1% (837)	1.2% (50)	<0.001
75–199		19.7% (7883)	16.2% (684)	<0.001
200–299		35.7% (14300)	38.1% (1609)	0.002
300–399		19.8% (7930)	20.4% (861)	0.359
400–499		12.1% (4854)	13.8% (583)	0.002
≥500		10.7% (4280)	10.3% (436)	0.495
Annual thrombolysis volume	0	33.5 (20.4–48.9)	36.9 (23.9–53.4)	<0.001
Teaching hospital	6509	57.3% (21964)	59.2% (2393)	0.018

Association Between Intravenous Thrombolysis and Primary Outcomes

In unadjusted logistic regression, intravenous thrombolysis was not associated with disposition to home (odds ratio [OR], 0.97 [95% CI, 0.90–1.04]) nor independent ambulation upon discharge (OR, 1.04 [95% CI, 0.95–1.13]). However, after adjusting for potential confounders, intravenous thrombolysis was associated with increased odds of discharge to home (adjusted OR [aOR], 1.33 [95% CI, 1.22–1.46]) and independent ambulation at discharge (aOR, 1.35 [95% CI, 1.21–1.50]) (Table 3).

Table 3.

Comparison of Primary and Safety Outcomes Across Both Groups (When Applicable)

	Nonthrombolysis	Thrombolysis	Unadjusted OR	Model 1 adjusted OR	Model 2 adjusted OR
Efficacy outcomes
Disposition home	49.9% (22 042/44 205)	49.0% (2304/4702)	0.97 (0.90–1.04)	1.31 (1.21–1.42)	1.33 (1.22–1.46)
Independent ambulation	49.4% (19 975/40 456)	50.3% (2174/4326)	1.04 (0.95–1.13)	1.33 (1.21–1.47)	1.35 (1.21–1.50)
Safety outcomes
Death or hospice	12.1% (5336/44 205)	11.7% (548/4702)	0.96 (0.87–1.07)	0.71 (0.63–0.79)	0.70 (0.62–0.80)
Symptomatic intracranial hemorrhage	Not applicable	3.5% (163/4671)	Not applicable		Not applicable
Systemic hemorrhage	Not applicable	0.5% (25/4671)	Not applicable		Not applicable

Model 1 adjusted for age and National Institutes of Health Stroke Scale score, and model 2 adjusted for age, sex, White race, Black race, Asian race, Hispanic ethnicity, National Institutes of Health Stroke Scale score, atrial fibrillation, hypertension, coronary artery disease/prior myocardial infarction, carotid stenosis, diabetes, smoking, hyperlipidemia, history of stroke, emergency medical services arrival, endovascular treatment, annual thrombolysis volume, hospital bed number and teaching status.

OR indicates odds ratio.

Safety Outcomes

The rate of symptomatic intracranial hemorrhage in patients who received thrombolysis was 3.5% (95% CI, 3.0%–4.1%) (163/4671) and the rate of systemic hemorrhage was 0.5% (95% CI, 0.4%–0.8%) (25/4671). In binary logistic regression analysis, the only factor associated with symptomatic intracranial hemorrhage was a higher NIHSS score (aOR, 1.05 per point [95% CI, 1.04–1.07], P<0.001). Furthermore, in adjusted analyses, thrombolysis was associated with lower risk of in‐hospital death or discharge to hospice (aOR, 0.70 [95% CI, 0.62–0.80]) (Table 3).

Sensitivity Analysis

In sensitivity analyses, the risk of symptomatic intracranial hemorrhage with thrombolysis increased with increasing NIHSS scores, but the association between thrombolysis and discharge to home and independent ambulation at discharge remained present across all NIHSS strata (Table 4).

Table 4.

Risks and Benefits of Intravenous Thrombolysis in NIHSS Strata

	Number of patients	Adjusted OR for independent ambulation	Adjusted OR for discharge home	sICH rate
NIHSS score 0–5	24 035	1.28 (1.10–1.50)	1.43 (1.23–1.66)	1.5% (22/1429)
NIHSS score 6–10	9058	1.43 (1.22–1.67)	1.40 (1.21–1.62)	2.4% (28/1171)
NIHSS score 11–15	5389	1.56 (1.28–1.91)	1.52 (1.26–1.83)	3.2% (25/787)
NIHSS score >15	9754	1.51 (1.26–1.81)	1.32 (1.12–1.56)	6.9% (88/1276)

NIHSS indicates National Institutes of Health Stroke Scale; OR, odds ratio; and sICH, symptomatic intracranial hemorrhage.

In sensitivity analyses excluding patients with relative contraindications to thrombolysis (Table S1), thrombolysis treatment remained associated with increased likelihood of home discharge (aOR, 1.40 [95% CI, 1.27–1.53]) and independent ambulation at discharge (aOR, 1.37 [95% CI, 1.23–1.52]).

Finally, in sensitivity analysis excluding patients not ambulating independently before the index ischemic stroke [4% (1397/36 005)], thrombolysis treatment remained associated with increased likelihood of home discharge (aOR, 1.25 [95% CI, 1.13–1.38]) and independent ambulation at discharge (aOR, 1.33 [95% CI, 1.18–1.50]).

Interaction Analyses

In interaction analyses, the benefit of thrombolysis appeared to be more pronounced in the subgroup of patients with NIHSS score ≥5 compared with those with NIHSS score <5 for the outcomes of independent ambulation at discharge (P for interaction <0.01) and for discharge to home (P for interaction <0.01) (Table 5).

Table 5.

Interaction Analyses Stratified by NIHSS Score (<5 and ≥5) and Endovascular Treatment

	Discharge home (IVT vs no IVT)	P interaction	Independent ambulation (IVT vs no IVT)	P interaction
Stratified by NIHSS score		<0.001		<0.001
NIHSS score <5	72.8% (1049/1441) vs 68.4% (15 458/22 594) Adjusted OR, 1.06 (95% CI, 0.94–1.20)		67.7% (975/1441) vs 62.2% (14 045/22 594) Adjusted OR, 1.06 (95% CI, 0.94–1.20)
NIHSS score ≥5	38.4% (1246/3243) vs 29.7% (6227/20 958) Adjusted OR, 1.39 (95% CI, 1.29–1.51)		36.8% (1192/3243) vs 27.1% (5673/20 958) Adjusted OR, 1.43 (95% CI, 1.32–1.56)
Stratified by EVT		0.499		0.392
EVT	34.2% (319/934) vs 29.0% (2034/7004) Adjusted OR, 1.38 (95% CI, 1.18–1.62)		33.8% (316/934) vs 29.8% (2087/7004) Adjusted OR, 1.26 (95% CI, 1.07–1.49)
No EVT	52.7% (1985/3768) vs 53.8% (20 008/37 201) Adjusted OR, 1.30 (95% CI, 1.20–1.40)		49.3% (1858/3770) vs 48.0% (17 891/37 243) Adjusted OR, 1.37 (95% CI, 1.27–1.48)

EVT indicates endovascular treatment; IVT, intravenous thrombolysis; NIHSS, National Institutes of Health Stroke Scale; and OR, odds ratio.

Inverse Probability of Treatment Weighting Analyses

In models weighted and adjusted for age and NIHSS score using inverse probability of treatment weighting, intravenous thrombolysis was associated with increased odds of independent ambulation at discharge (aOR, 1.27 [95% CI, 1.15–1.39], P<0.001) and home discharge (aOR, 1.23 [95% CI, 1.14–1.34], P<0.001) as well as reduced odds of in‐hospital death or discharge to hospice (aOR, 0.74 [95% CI, 0.66–0.83], P<0.001). In binary logistic regression models weighted and adjusted for age, NIHSS score, ambulatory status before admission, admission year, annual intravenous thrombolysis volume, sex, atrial fibrillation, diabetes, peripheral vascular disease, hyperlipidemia, heart failure, and INR, annual intravenous thrombolysis volume was associated with increased odds of independent ambulation at discharge (aOR, 1.15 [95% CI, 1.04–1.27], P=0.007) and home discharge (aOR, 1.25 [95% CI, 1.13–1.38], P<0.001). Post weighting, standardized mean differences were all <0.1 except for NIHSS and INR, which were 0.17 and −0.203, respectively (Table S2).

DISCUSSION

In this US nationwide registry‐based analysis of patients with ischemic stroke with recent DOAC use, intravenous thrombolysis was associated with improved functional outcome at discharge compared with withholding thrombolysis. This finding was more pronounced in patients with baseline NIHSS score ≥5 and did not differ by whether the patient underwent endovascular treatment or not. The rate of symptomatic intracranial hemorrhage in those receiving intravenous thrombolysis was comparable to the previously reported national average in non‐DOAC patients treated with thrombolysis, which is 3.5%. ¹¹ , ¹³

These findings are timely and relevant due to the high rates of morbidity and mortality in patients with acute ischemic stroke on DOACs. ⁶ , ¹⁴ In a single‐center study of 44 consecutive patients excluded from thrombolysis due to recent DOAC ingestion, nearly 70% of patients had death or disability at 90 days (modified Rankin Scale score, 3–6) and almost 35% of patients died within 90 days with 77% of the deaths being stroke related. Similarly, data from a multicenter study showed that among 1409 anticoagulated patients with ischemic stroke in the setting of atrial fibrillation, 69% had death or disability at 90 days. ¹⁴

Another compelling reason to suggest that thrombolysis is safe in patients with recent DOAC ingestion is that DOACs have a short half‐life in patients with normal kidney function (10–12 hours). Thus, beyond 12 hours, the anticoagulation effect and drug level may be low enough to safely allow thrombolysis. ¹⁵ , ¹⁶ Current guidelines, however, suggest near complete drug elimination (4–5 half‐lives) to consider thrombolysis treatment. ³

Observational data suggest that intravenous thrombolysis may be safe in select patients using DOACs within 48 hours of hospital arrival, with or without use of predefined drug levels or calibrated anti‐factor‐Xa activity. ¹⁷ In one large case–control multicenter international study, the risk of symptomatic intracranial hemorrhage with intravenous thrombolysis was lower in 832 patients with DOAC use within 48 hours compared with 32 375 patients without DOAC use within 48 hours (aOR, 0.57 95% CI, 0.36–0.92). ¹⁸ Among patients with DOAC use, 252 (30.3%) received DOAC reversal before intravenous thrombolysis (all idarucizumab), 225 (27.0%) had DOAC‐level measurements, and 355 (42.7%) received thrombolysis without measuring DOAC plasma levels or reversal treatment. ¹⁸

In meta‐analyses of observational studies, the symptomatic intracranial hemorrhage risk following thrombolysis was similar across patients with acute ischemic stroke taking a DOAC, vitamin K antagonist with INR ≤1.7, or no anticoagulant. ¹³ , ¹⁹ Moreover, in a study from GWTG of 163 038 patients treated with intravenous alteplase (median age, 70 [IQR, 59–81] years; 49.1% women), 2207 (1.4%) were taking DOACs. ¹¹ After adjusting for baseline clinical factors, the risk of symptomatic intracranial hemorrhage was not significantly different between groups (aOR, 0.88 [95% CI, 0.70–1.10]). ¹¹ Finally, a single‐center study from Asia showed that among patients on DOACs receiving thrombolysis, the rate of intracranial hemorrhage was higher in patients ≤4 hours from last intake than those >4 hours (38% versus 10%, P=0.033). ²⁰

Our study adds to the body of literature on the potential efficacy of thrombolysis in patients with recent DOAC ingestion. There are, however, several major limitations. First, we did not capture the exact timing of last DOAC ingestion including whether it occurred within the past 48 versus 49 hours to 7 days. Prior analysis from GWTG data linking GWTG patients with the ARAMIS registry found that 53% of such patients had recent DOAC ingestion within 48 hours of hospital arrival and did not show differences in symptomatic intracranial hemorrhage rates between patients treated within 48 hours and beyond 48 hours. ¹¹ Second, our study is observational and not randomized and thus subject to confounding bias. Despite adjusting for several potential confounders and covariates, we cannot eliminate the possibility of residual or unmeasured confounding. Third, we lack granular data on the type of DOAC used and thus we are unable to determine whether the risks and benefits apply to all DOACs. Fourth, we have data on discharge outcomes but not 90‐day outcomes. Discharge outcomes have been shown to correlate with 90‐day outcomes, however. ²¹ , ²² , ²³ Finally, a large number of patients were excluded due to missing data on at least 1 major contraindication (49 657 patients) or intravenous thrombolysis status (14 839 patients) as well as the number of patients with missing variables such as body mass index, systolic blood pressure, and diastolic blood pressure, which is an inherent limitation of the Get With The Guidelines database, and thus our findings should be interpreted with caution.

CONCLUSIONS

In this analysis from GWTG registry, intravenous thrombolysis was associated with improved functional outcome in patients with recent DOAC use. Given the limitations of our analysis, these findings require validation by prospective randomized trials with low risk of bias.

Sources of Funding

The GWTG‐Stroke (Get With The Guidelines–Stroke) program is provided by the American Heart Association. GWTG‐Stroke is sponsored, in part, by Novartis, Novo Nordisk, AstraZeneca, Bayer and HCA Healthcare.

Disclosures

None.

Supporting information

Tables S1–S2