These authors contributed equally to the manuscript as first author.
Mechanical thrombectomy (MT) is an effective treatment for patients with basilar artery occlusion (BAO) acute ischemic stroke. It remains unclear whether bridging intravenous thrombolysis (IVT) prior to MT confers any benefit. This study compared the outcomes of acute BAO patients who were treated with direct MT versus combined IVT plus MT.
This multicenter retrospective cohort study included patients who were treated for acute BAO from eight comprehensive stroke centers between January 2015 and December 2019. Patients received direct MT or combined bridging IVT plus MT. Primary outcome was favorable functional outcome defined as modified Rankin Scale 0–3 measured at 90 days. Secondary outcome measures included mortality and symptomatic intracranial hemorrhage (sICH).
Among 322 patients, 127 (39.4%) patients underwent bridging IVT followed by MT and 195 (60.6%) underwent direct MT. The mean±standard deviation age was 67.5±14.1 years, 64.0% were male and median National Institutes of Health Stroke Scale was 16 (interquartile range, 8 to 25). At 90-day, the rate of favorable functional outcome was similar between the bridging IVT and direct MT groups (39.4% vs. 34.4%,
Functional outcomes were similar in BAO patients treated with bridging IVT versus direct MT. In the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT may potentially confer benefit and this warrants further investigation.
Acute basilar artery occlusion (BAO) is a cerebrovascular emergency that still causes devastating rates of morbidity and mortality despite the advances in acute ischemic stroke (AIS) care [
Pooled analyses from several studies provide conflicting results regarding the efficacy of bridging IVT, with some studies reporting equivalent effects achieved in bridging IVT and direct MT [
We therefore performed a multicenter retrospective cohort study conducted across comprehensive stroke centers in Europe and Asia to determine whether outcomes of direct MT alone would be comparable to bridging IVT plus MT treatment in patients with BAO AIS.
This retrospective cohort study was approved by the Institutional Review Boards (IRB) of each respective institution. Waiver of individual participant consent was granted.
Consecutive patients from eight comprehensive stroke centers across five countries (
At all centers, patients were considered eligible for MT if the procedure could be initiated within 24 hours of the time of stroke onset and had an angiographically confirmed occlusion in the basilar artery. Patients were excluded from thrombectomy when pre-treatment imaging revealed extensive ischemic changes in the brainstem, or if the stroke was considered mild, based on an admission National Institutes of Health Stroke Scale (NIHSS) score of 3 or less. There was no upper limit on either the age of the patient or admission NIHSS score for inclusion across all centers.
Clinical monitoring was performed in either the intensive care unit or high dependency unit setting during the initial acute episode. All patients were managed according to international guidelines for the management of AIS [
The following epidemiological information was extracted from patient records: age, sex, race, and smoking history. Comorbidities studied included hypertension, hyperlipidaemia, diabetes mellitus, atrial fibrillation, and previous ischemic stroke. The mechanism of ischemic stroke was defined according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification [
The primary outcome measure was a favorable functional outcome defined as a mRS ≤3 after 90 days [
Numeric variables were first tested for normality with the Shapiro-Wilk test. A Student’s t-test was used for normally distributed data and a Mann-Whitney U test for non-normally distributed data. Categorical variables were compared using a Pearson chi-square test, with computation of Wald and score 95% confidence interval (CI) for the incidence odds ratio (OR). Subsequently, multivariable logistic regression was carried out to identify predictors for primary and secondary outcome measures. In addition, the following exploratory subgroup analyses were performed: (1) age 75 years or younger vs. older than 75 years; (2) male vs. female sex; and (3) TOAST mechanism of large-artery atherosclerosis (LAA) vs. non-LAA strokes.
A total of 322 patients were included in the study. Of these patients, 127 (39.4%) underwent bridging IVT prior to MT while 195 (60.6%) underwent direct MT. The baseline characteristics of the bridging IVT group and direct MT group were comparable, with similar age, race, and comorbidity profile. Notably, there were more males in the direct MT group (68.2%) compared to the bridging IVT group (57.5%) (
Stroke severity as measured by median NIHSS was 16 on admission, and was marginally lower in the bridging IVT group compared to the direct MT group (14 vs. 17,
The rate of favorable functional outcome at 90 days was similar between the direct MT and bridging IVT groups (34.4% vs. 39.4%,
Secondary outcomes were largely similar between the direct MT group and the bridging IVT group, with the exception of discharge mRS (
After adjustment for age, sex, NIHSS, and time from stroke onset to groin puncture in the multivariable model, the association between bridging IVT and favorable functional outcome upon discharge lost significance (OR, 1.60; 95% CI, 0.82 to 3.10;
A significant treatment effect of bridging IVT was observed in the subgroup of patients who had underlying LAA (
In all other subgroup analyses performed, there were no significant differences in the rates of favorable functional outcome at 90 days between the bridging IVT group and the direct MT group (
In this study, we did not observe a significant improvement in outcomes for BAO AIS patients who received combined bridging IVT and MT, compared to direct MT alone. However in a subgroup analysis, we found that bridging IVT prior to MT was associated with better functional outcomes in patients with BAO due to underlying LAA.
In the recently published Basilar Artery International Cooperation Study (BASICS) trial, 44.2% of patients with best medical management in addition to MT achieved favorable mRS scores (mRS 0–3) at 90 days post-discharge compared to 37.7% of those managed with best medical treatment alone [
Currently, there is a paucity of evidence comparing direct MT and bridging IVT in the treatment of acute BAO, with no consensus on the optimal clinical management of this condition [
Recent trials also support our findings that bridging IVT does not improve long-term patient outcomes [
Interestingly, our study found that patients with LAA appeared to benefit from bridging IVT. In LAA, the existing narrowing of cerebral vessels triggers the formation of collateral vessels over time [
The limitations of our study stem from its retrospective non-randomized nature. Firstly, a difference in stroke onset to groin puncture time was noted between the bridging thrombolysis group and direct MT group, which was adjusted for in the multivariable analyses. Secondly, treatment allocations were made at the discretion of the treating stroke neurologist and neurointerventionist. This may introduce selection bias as different centers may have had different clinical practices. In our study cohort, 76.4% of bridging IVT (n=97/127) patients and around half of the patients in the direct MT group (50.3%; n=98/195) had onset to groin puncture time within 4.5 hours. This reflects a large proportion of patients in the direct MT group that presented early enough to be treated with bridging IVT; however, the attending stroke neurologist elected to forgo bridging IVT. Unfortunately, we did not collect the specific reasons for not administering IVT in this retrospective study. Nonetheless, our findings are reflective of real-world treatment paradigms as they reflect the same inconsistencies observed in treatment allocations by different physicians even within the same center, facilitating our improved understanding of the appropriate therapeutic strategies. Finally, the lack of statistical significance reported for the primary study outcome could be a function and limitation of the moderate sample size. Our study included a total of 322 acute BAO patients who underwent MT, which is a respectable cohort size in view that the procedure is less commonly performed for BAO in comparison to anterior circulation LVO. This sample size is also comparable to recently published bridging IVT versus direct MT randomized controlled trials for anterior circulation LVO [
In patients with AIS due to BAO, bridging IVT was not associated with improved functional outcomes at 90-day. However, in patients with underlying LAA, a significant treatment effect of bridging IVT was observed. The equipoise to whether bridging IVT provides additional benefits over direct MT should be resolved in future randomized controlled studies.
Supplementary materials related to this article can be found online at
Participating study institutions across five countries
Comparing 90-day functional outcomes of bridging IVT vs. direct MT in subgroup analyses
The authors have no financial conflicts of interest.
Ordinal shift analysis comparing 90-day modified Rankin Scale scores in patients with basilar artery occlusion acute ischemic stroke and underlying large-artery atherosclerosis who underwent bridging intravenous thrombolysis (IVT) versus direct mechanical thrombectomy (MT). OR, odds ratio; CI, confidence interval.
Baseline characteristics of study population (n=322)
Characteristic | Total (n=322) | Bridging IVT (n=127) | Direct MT (n=195) | ||
---|---|---|---|---|---|
Age (yr) | 67.5±14.1 | 69.4±14.0 | 66.3±14.0 | 0.054 | |
Sex | 0.050 | ||||
Male | 206 (64.0) | 73 (57.5) | 133 (68.2) | ||
Female | 116 (36.0) | 54 (42.5) | 62 (31.8) | ||
Country | - | ||||
Germany | 138 (42.9) | 65 (51.2) | 73 (37.4) | ||
United Kingdom | 10 (3.1) | 2 (1.6) | 8 (4.1) | ||
Singapore | 67 (20.8) | 33 (26.0) | 34 (17.4) | ||
Taiwan | 46 (14.3) | 7 (5.5) | 39 (20.0) | ||
Sweden | 61 (18.9) | 20 (15.7) | 41 (21.0) | ||
Race | 0.275 | ||||
Caucasian | 209 (64.9) | 87 (68.5) | 122 (62.6) | ||
Asian | 113 (35.1) | 40 (31.5) | 73 (37.4) | ||
Hypertension | 198/260 (76.2) | 88/106 (83.0) | 110/154 (71.4) | 0.031 | |
Hyperlipidaemia | 83/256 (32.4) | 38/103 (36.9) | 45/153 (29.4) | 0.210 | |
Diabetes mellitus | 75/260 (28.8) | 31/106 (29.2) | 44/154 (28.6) | 0.909 | |
Atrial fibrillation | 77/260 (29.6) | 27/106 (25.5) | 50/154 (32.5) | 0.225 | |
Previous stroke | 34/215 (15.8) | 16/86 (18.6) | 18/129 (14.0) | 0.360 | |
TOAST classification | 0.410 | ||||
Large-artery atherosclerosis | 101 (31.4) | 43 (33.9) | 58 (29.7) | ||
Cardioembolic | 137 (42.5) | 47 (37.0) | 90 (46.2) | ||
Stroke of other determined aetiology | 12 (3.7) | 6 (4.7) | 6 (3.1) | ||
Stroke of undetermined aetiology | 72 (22.4) | 31 (24.4) | 41 (21.0) | ||
Admission NIHSS | 16 (8–25) | 14 (8–22) | 17 (8–26) | 0.092 | |
Time from stroke onset to groin puncture (min) | 270 (180–420) | 240 (180–300) | 330 (180–518) | 0.002 | |
Time from groin puncture to reperfusion (min) | 60 (30–90) | 60 (30–82) | 60 (30–90) | 0.670 |
Values are presented as mean±standard deviation, number (%), or median (interquartile range).
IVT, intravenous thrombolysis; MT, mechanical thrombectomy; TOAST, Trial of Org 10172 in Acute Stroke Treatment; NIHSS, National Institutes of Health Stroke Scale.
Comparison of outcomes between direct MT and bridging IVT groups (n=322)
Outcome | Total (n=322) | Bridging IVT (n=127) | Direct MT (n=195) | |||
---|---|---|---|---|---|---|
Primary outcome | ||||||
90-Day mRS | 0.361 | |||||
0–3 (favorable) | 117 (36.3) | 50 (39.4) | 67 (34.4) | |||
4–6 (unfavorable) | 205 (63.7) | 77 (60.6) | 128 (65.6) | |||
Secondary outcomes | ||||||
In-hospital mortality | 0.226 | |||||
Survival | 245 (76.1) | 102 (80.3) | 143 (73.3) | |||
Death | 77 (23.9) | 25 (19.7) | 52 (26.7) | |||
90-Day mRS | 0.593 | |||||
0–2 (good) | 91 (28.3) | 38 (29.9) | 53 (27.2) | |||
3–6 (poor) | 231 (71.7) | 89 (70.1) | 142 (72.8) | |||
Discharge mRS | 0.047 | |||||
0–3 (favorable) | 73/261 (28.0) | 37/107 (34.6) | 36/154 (23.4) | |||
4–6 (unfavorable) | 188/261 (72.0) | 70/107 (65.4) | 118/154 (76.6) | |||
mTICI post-treatment | 0.110 | |||||
0–2a (poor) | 45/320 (14.1) | 13/127 (10.2) | 32/193 (16.6) | |||
2b–3 (good) | 275/320 (85.9) | 114/127 (89.8) | 161/193 (83.4) | |||
mTICI post-treatment | 0.275 | |||||
0–2b (poor) | 120/320 (37.5) | 43/127 (33.9) | 77/193 (39.9) | |||
2c–3 (good) | 200/320 (62.5) | 84/127 (66.1) | 116/193 (60.1) | |||
sICH 24-hour post-intervention | 14/299 (4.7) | 6/119 (5.0) | 8/180 (4.4) | 0.811 | ||
Subarachnoid hemorrhage | 9/264 (3.4) | 3/99 (3.0) | 6/165 (3.6) | 1.000 |
Values are presented as number (%).
MT, mechanical thrombectomy; IVT, intravenous thrombolysis; mRS, modified Rankin Scale; mTICI, modified Thrombolysis in Cerebral Infarction; sICH, symptomatic intracranial hemorrhage.
Comparison of outcomes between bridging IVT and direct MT groups
Outcome | OR (95% CI) | |
---|---|---|
90-Day mRS | 1.21 (0.67–2.18) | 0.524 |
Discharge mRS | 1.60 (0.82–3.10) | 0.169 |
In-hospital mortality | 0.74 (0.38–1.45) | 0.383 |
Post-treatment mTICI 2b–3 | 2.33 (0.98–5.53) | 0.056 |
sICH 24-hour post-intervention | 1.65 (0.49–5.59) | 0.422 |
Subarachnoid hemorrhage | 0.96 (0.20–4.54) | 0.955 |
Adjusted for age, sex, National Institutes of Health Stroke Scale and time from stroke onset to groin puncture.
IVT, intravenous thrombolysis; MT, mechanical thrombectomy; OR, odds ratio; CI, confidence interval; mRS, modified Rankin Scale; mTICI, modified Thrombolysis in Cerebral Infarction; sICH, symptomatic intracranial hemorrhage.
Subgroup analysis comparing outcomes of bridging IVT vs. direct MT in basilar artery occlusion patients with underlying large-artery atherosclerosis (n=101)
Outcome | Total (n=101) | Bridging IVT (n=43) | Direct MT (n=58) | OR (95% CI) | ||
---|---|---|---|---|---|---|
90-Day mRS | 3.23 (1.26–8.28) | 0.013 | ||||
0–3 (favorable) | 25 (24.8) | 16 (37.2) | 9 (15.5) | |||
4–6 (unfavorable) | 76 (75.2) | 27 (62.8) | 49 (84.5) | |||
90-Day mRS | 4.10 (1.32–12.75) | 0.010 | ||||
0–2 (good) | 17 (16.9) | 12 (27.9) | 5 (8.6) | |||
3–6 (poor) | 84 (83.2) | 31 (72.1) | 53 (91.4) | |||
Discharge mRS | 6.28 (2.08–18.98) | <0.001 | ||||
0–3 (good) | 21 (20.8) | 16 (37.2) | 5 (8.6) | |||
4–6 (poor) | 80 (79.2) | 27 (72.8) | 53 (91.4) | |||
In-hospital mortality | 0.34 (0.13–0.90) | 0.027 | ||||
Survival | 73 (72.3) | 36 (83.7) | 37 (63.8) | |||
Death | 28 (27.7) | 7 (16.3) | 21 (36.2) | |||
mTICI post-treatment | 2.07 (0.51–8.33) | 0.346 | ||||
0–2a (poor) | 11 (10.9) | 3 (7.0) | 8 (13.8) | |||
2b–3 (good) | 90 (89.1) | 40 (93.0) | 50 (86.2) | |||
mTICI post-treatment | 1.89 (0.81–4.43) | 0.117 | ||||
0–2b (poor) | 37 (36.6) | 12 (27.9) | 25 (43.1) | |||
2c–3 (good) | 64 (63.4) | 31 (72.1) | 33 (56.9) | |||
sICH 24-hour post-intervention | 7 (6.9) | 3 (7.0) | 4 (6.9) | 1.01 (0.22–4.78) | 1.000 | |
Subarachnoid hemorrhage | 2 (2.0) | 1 (2.3) | 1 (1.7) | 1.36 (0.08–22.33) | 1.000 |
Values are presented as number (%).
IVT, intravenous thrombolysis; MT, mechanical thrombectomy; OR, odds ratio; CI, confidence interval; mRS, modified Rankin Scale; mTICI, modified Thrombolysis in Cerebral Infarction; sICH, symptomatic intracranial hemorrhage.