This study aimed to investigate the role of antiplatelet agents (APAs) in preventing cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (SAH) patients treated with coil embolization.
: We reviewced data from 131 consecutive patients who underwent coil embolization following aneurysmal SAH from January 2011 to May 2021. We finally recruited 108 patients and analyzed the occurrence of CVS and DCI, as well as the modified Rankin Scale (mRS) score at discharge according to the use of APA (APA group [n=32] vs. non-APA group [n=76]).
The baseline characteristics, except patient age, were not significantly different between the APA and the non-APA groups. DCI (p=0.846), transcranial Doppler ultrasonographic vasospasm (p=0.449), angiographic vasospasm (p=0.176), and mRS scores at discharge (p=0.194) were also not significantly different between the groups. Newly developed cerebral infarction was significantly more frequent in the APA group (p=0.027).
APA use did not reduce the occurrence of CVS and DCI in aneurysmal SAH patients treated with coil embolization, indicating that the effect of APAs on clinical outcomes may be trivial compared with other risk factors.
Delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) following aneurysmal subarachnoid hemorrhage (SAH) are serious complications occurring within the first 2 weeks after ictus and lead to significant disabilities, worsening quality of life and even death. CVS is the phenomenon of arterial narrowing observed on angiography. The term “symptomatic vasospasm” is commonly used when clinical deterioration is related to CVS. Meanwhile, DCI is characterized by a new neurological deficit or decreased consciousness that should not have been apparent immediately after aneurysm occlusion and should not be attributable to other causes
Recently, an increasing body of evidence has demonstrated that DCI does not always correlate with the vascular distribution of CVS, and DCI could occur without CVS
With the advent of endovascular aneurysm treatment, a growing number of SAH patients require APA medication following intervention due to stent or thromboembolic risk. The purpose of this study was to determine whether APA reduces the incidence of CVS or DCI in aneurysmal SAH patients treated using an endovascular tool.
The study protocol was approved by the Institutional Review Board (IRB). The requirement of obtain written informed consent to participate in this study was waived by IRB. We reviewed 131 consecutive patients who underwent coil embolization following aneurysmal SAH from January 2011 to May 2021. We divided the patients into two groups according to the use of APA following endovascular treatment. The use of APA was decided by the attending interventionist depending on the use of stent and the risk of thromboembolic event (coil protrusion into parent vessel). Patients receiving APA after coil embolization were assigned to the APA group and patients who were managed without APA were included in the non-APA group.
The exclusion criteria for this study were no transcranial Doppler ultrasonography (TCD) data, early death within 7 days after ictus, and insufficient clinical data. We eventually recruited 108 patients. We retrospectively collected the following data: age, sex, history of hypertension and diabetes mellitus, Hunt–Hess grade, modified Fisher grade, aneurysm location, newly developed cerebral infarction, newly developed hemorrhage, and the occurrence of DCI, TCD vasospasm, and angiographic vasospasm. First, we analyzed the clinical parameters associated with the clinical outcome (modified Rankin Scale [mRS] scores); then, we analyzed the occurrence of TCD vasospasm and DCI and the mRS score at discharge according to the use of APA.
All patients underwent TCD every other day for 14 days and TCD vasospasm was defined as a mean velocity of the middle cerebral artery >120 cm. Angiographic vasospasm was defined as the narrowing of the vessel lumen by greater than 25% of the original vessel diameter on digital subtraction angiography (DSA). We only performed DSA when TCD vasospasm with clinical deterioration was identified. DCI was defined as the occurrence of clinical deterioration, such as aphasia or hemiparesis, and a decrease in the level of consciousness that were not apparent immediately after aneurysm embolization and were not attributed to other causes in radiological and laboratory studies
Before coil embolization, we evaluated 3-dimensional computed tomographic angiography and predicted the possible use of a stent. Those patients were administered 400 mg of aspirin as a loading dose. Heparin (2,000 IU) was administered as a bolus after angiography and intermittently 1,000 IU bolus per hr until the end of the procedure. In the case of stent-assisted coil embolization and coil protrusion into the parent vessel, aspirin 100 mg and clopidogrel 75 mg were administered daily for at least 12 weeks and aspirin was maintained lifelong after the procedure. The platelet function test was not routinely used.
Continuous variables are presented as the mean (with standard deviation) and categorical variables are presented as the number of cases. For the comparison of baseline variables, the χ2 test and Fisher’s exact test were used for categorical variables, and Student’s
Among 108 patients (70 women, 64.8%) with a mean age of 57.6 ± 13.4 years (range, 23–91 years), 32 patients were allocated to the APA group and 76 patients to the non-APA group.
Unfavorable clinical outcome (mRS scores at discharge 0–2) was significantly associated with old age (p=0.000), diabetes mellitus (p=0.049), Hunt–Hess grade (p=0.000), modified Fisher grade (p=0.034), location of the aneurysm (p=0.048), newly developed cerebral infarction (p=0.000), newly developed hemorrhage (p=0.000), and DCI (p=0.000) (
Baseline characteristics, except patient age were not significantly different between the APA and the non-APA groups (
This study did not show a beneficial effect of APA on the occurrence of TCD vasospasm, angiographic vasospasm, and DCI; rather it showed a significantly negative effect. Also, clinical outcomes in patients who received APA were significantly worse. However, risk factors for unfavorable clinical outcomes (old age, newly developed infarction, and DCI) were consistent with those of previous studies. Therefore, it is presumed that the baseline characteristics of study population were not different from those of previous studies.
To date, the beneficial effect of APA on the occurrence of CVS and DCI in aneurysmal SAH patients is controversial. This discrepancy is attributed to heterogenous study designs and inconsistency of the definition of DCI. An international ad hoc panel of experts proposed a definition of DCI be used as an outcome measure and recommended restricting the use of “vasospasm” in descriptions of radiological tests
The main limitation of this study is its retrospective design and small sample size. In addition, we excluded the patients treated by surgical clipping. Therefore, the results could not be generalized to all aneurysmal SAH patients. Moreover, it is difficult to detect CVS or DCI in poor-grade SAH patients. Although TCD is a simple, non-invasive, bedside test, and increased blood flow velocity on TCD is useful as a surrogated tool, it has a lower power to diagnose CVS than angiography
In this study, there was no evidence that the use of APA decreased the occurrence of CVS and DCI in aneurysmal SAH patients treated by endovascular tools, indicating that the effect of APA on clinical outcomes may be trivial compared with other risk factors. Future studies should focus on the dosage and kinds of APA to elucidate the role of APA in the management of aneurysmal SAH.
The study protocol conformed to the ethical guidelines of the World Medical Association Declaration of Helsinki and was approved by the Institutional Review Board.
No potential conflict of interest relevant to this article was reported.
Baseline characteristics of the study population related to clinical outcomes at discharge
Characteristic | mRS score 0–2 (n = 80) | mRS score 3–6 (n = 28) | p-value |
---|---|---|---|
Sex | 0.323 | ||
Male | 26 (32.5) | 12 (42.9) | |
Female | 54 (67.5) | 16 (57.1) | |
Age (year) | 54.5 ± 11.5 | 66.6 ± 14.6 | |
Age (year) | |||
<60 | 57 (71.2) | 10 (35.7) | |
≥60 | 23 (28.8) | 18 (64.3) | |
Hypertension | 0.213 | ||
Yes | 32 (40.0) | 15 (53.6) | |
No | 48 (60.0) | 13 (46.4) | |
Diabetes mellitus | |||
Yes | 4 (5.0) | 5 (17.9) | |
No | 76 (95.0) | 23 (82.1) | |
Hunt-Hess grade | |||
1 | 1 (1.3) | 0 (0.0) | |
2 | 51 (63.8) | 7 (25.0) | |
3 | 26 (32.5) | 13 (46.4) | |
4 | 2 (2.5) | 8 (28.6) | |
5 | 0 (0.0) | 0 (0.0) | |
Hunt-Hess grade | |||
Grade 1-3 | 78 (97.5) | 20 (71.4) | |
Grade 4-5 | 2 (2.5) | 8 (28.6) | |
Modified Fisher grade | 0.100 | ||
1 | 8 (10.0) | 0 (0.0) | |
2 | 4 (5.0) | 0 (0.0) | |
3 | 32 (40.0) | 9 (32.1) | |
4 | 36 (45.0) | 19 (67.9) | |
Modified Fisher grade | |||
Grade 1-2 | 12 (15.0) | 0 (0.0) | |
Grade 3-4 | 68 (85.0) | 28 (100.0) | |
Location of the aneurysm | |||
ACA | 16 (20.0) | 13 (46.4) | |
ICA | 53 (66.3) | 12 (42.9) | |
MCA | 1 (1.3) | 0 (0.0) | |
VBS | 10 (12.5) | 3 (10.7) | |
Location of the aneurysm | 1.000 | ||
Anterior circulation | 70 (87.5) | 25 (89.3) | |
Posterior circulation | 10 (12.5) | 3 (10.7) | |
TCD vasospasm | 0.811 | ||
Yes | 21 (26.3) | 8 (28.6) | |
No | 59 (73.8) | 20 (71.4) | |
Angiographic vasospasm | 0.648 | ||
Yes | 4 (5.0) | 2 (7.1) | |
No | 76 (95.0) | 26 (92.9) | |
DCI | |||
Yes | 8 (10.0) | 21 (75.0) | |
No | 72 (90.0) | 7 (25.0) | |
New cerebral infarction | |||
Yes | 5 (6.3) | 15 (53.6) | |
No | 75 (93.8) | 13 (46.4) | |
New hemorrhage | |||
Yes | 1 (1.3) | 7 (25.0) | |
No | 79 (98.8) | 21 (75.0) |
The data is presented as number (%) or mean ± standard deviation.
mRS: modified Rankin Scale; ACA: anterior cerebral artery; ICA: internal carotid artery; MCA: middle cerebral artery; VBS: vertebrobasilar system; TCD: transcranial doppler; DCI: delayed cerebral ischemia.
Risk factors for unfavorable clinical outcomes
Parameter | OR (95% CI) | p-value |
---|---|---|
Age ≥ 60 years | 14.173 (1.644–112.176) | 0.016 |
Newly developed CI | 6.376 (1.209–33.637) | 0.029 |
DCI | 57.593 (6.071–546.356) | 0.000 |
OR: odds ratio; CI: confidence interval; CI: cerebral infarction; DCI: delayed cerebral ischemia.
Baseline characteristics of patients in the APA and nAPA groups
Characteristic | APA group (n = 32) | non-APA group (n = 76) | p-value |
---|---|---|---|
Sex | 0.442 | ||
Male | 13 (40.6) | 25 (32.9) | |
Female | 19 (59.4) | 51 (67.1) | |
Age (year) | 62.4 ± 14.4 | 55.6 ± 12.6 | |
Age (year) | |||
<60 | 15 (46.9) | 52 (68.4) | |
≥60 | 17 (53.1) | 24 (31.6) | |
Hypertension | 0.191 | ||
Yes | 17 (53.1) | 30 (39.5) | |
No | 15 (46.9) | 46 (60.5) | |
Diabetes mellitus | 1.000 | ||
Yes | 2 (6.3) | 7 (9.2) | |
No | 30 (93.8) | 69 (90.8) | |
Hunt-Hess grade | 0.766 | ||
1 | 0 (0.0) | 1 (1.3) | |
2 | 16 (50.0) | 42 (55.3) | |
3 | 12 (37.5) | 27 (35.5) | |
4 | 4 (12.5) | 6 (7.9) | |
5 | 0 (0.0) | 0 (0.0) | |
Hunt-Hess grade | 0.478 | ||
Grade 1-3 | 28 (87.5) | 70 (92.1) | |
Grade 4-5 | 4 (12.5) | 6 (7.9) | |
Modified Fisher grade | 0.113 | ||
1 | 3 (9.4) | 5 (6.6) | |
2 | 1 (3.1) | 3 (3.9) | |
3 | 7 (21.9) | 34 (44.7) | |
4 | 21 (65.6) | 34 (44.7) | |
Modified Fisher grade | 0.747 | ||
Grade 1-2 | 4 (12.5) | 8 (10.5) | |
Grade 3-4 | 28 (87.5) | 68 (89.5) | |
Location of the aneurysm | 0.096 | ||
ACA | 4 (12.5) | 25 (32.9) | |
ICA | 23 (71.9) | 42 (55.3) | |
MCA | 0 (0.0) | 1 (1.3) | |
VBS | 5 (15.6) | 13 (17.1) | |
Location of the aneurysm | 0.521 | ||
Anterior circulation | 27 (84.4) | 68 (89.5) | |
Posterior circulation | 5 (15.6) | 8 (10.5) |
The data is presented as number (%) or mean ± standard deviation.
APA: antiplatelet agent; ACA: anterior cerebral artery; ICA: internal carotid artery; MCA: middle cerebral artery; VBS: vertebrobasilar system.
Clinical characteristics of patients in the APA and nAPA groups
Characteristic | APA group (n = 32) | non-APA group (n = 76) | p-value |
---|---|---|---|
TCD vasospasm | 0.449 | ||
Yes | 7 (21.9) | 22 (28.9) | |
No | 25 (78.1) | 54 (71.1) | |
Angiographic vasospasm | 0.176 | ||
Yes | 0 (0.0) | 6 (7.9) | |
No | 32 (100.0) | 70 (92.1) | |
DCI | 0.846 | ||
Yes | 9 (28.1) | 20 (26.3) | |
No | 23 (71.9) | 56 (73.7) | |
New cerebral infarction | |||
Yes | 10 (31.3) | 10 (13.2) | |
No | 22 (68.8) | 66 (86.8) | |
New hemorrhage | 0.432 | ||
Yes | 1 (3.1) | 7 (9.2) | |
No | 31 (96.9) | 69 (90.8) | |
mRS score at discharge | 0.512 | ||
0 | 8 (25.0) | 27 (35.5) | |
1 | 12 (37.5) | 23 (30.3) | |
2 | 1 (3.1) | 9 (11.8) | |
3 | 3 (9.4) | 5 (6.6) | |
4 | 3 (9.4) | 4 (5.3) | |
5 | 2 (6.3) | 5 (6.6) | |
6 | 3 (9.4) | 3 (3.9) | |
mRS score at discharge | 0.194 | ||
Favorable (mRS 0–2) | 3 (9.4) | 4 (5.3) | |
Unfavorable (mRS 3–6) | 29 (90.6) | 72 (94.7) | |
Mortality | 0.358 | ||
Yes | 3 (9.4) | 3 (3.9) | |
No | 29 (90.6) | 73 (96.1) |
APA: antiplatelet agent; TCD: transcranial doppler; DCI: delayed cerebral ischemia; mRS: modified Rankin Scale.