Efficacy and safety of mechanical thrombectomy in distal medium middle cerebral artery occlusion ischemic stroke patients on low-dose aspirin

Abstract

Background:

Acute ischemic stroke (AIS) from distal medium vessel occlusion (DMVO) presents unique treatment challenges. Mechanical thrombectomy (MT) is emerging as a viable option for these patients, yet the role of pre-stroke aspirin treatment is unclear. This study evaluates the impact of pre-stroke low-dose aspirin on outcomes in DMVO patients undergoing MT.

Methods:

We conducted a multinational, multicenter, propensity score-weighted analysis within the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry. Patients with AIS due to DMVO, treated with MT, were included. We compared outcomes between patients on pre-stroke low-dose aspirin (75–100 mg) and those not on antiplatelet therapy. The primary outcome was functional independence at 90 days (modified Rankin Scale (mRS), 0–2). Secondary outcomes included excellent functional outcome at 90 days (mRS, 0–1), mortality, and day 1 post-MT National Institutes of Health Stroke Scale (NIHSS) score. Safety outcomes focused on hemorrhagic complications, including symptomatic intracerebral hemorrhage (sICH).

Results:

Among 1354 patients, 150 were on pre-stroke low-dose aspirin. After applying inverse probability of treatment weighting (IPTW), aspirin use was associated with significantly better functional outcomes (mRS, 0–2: odds ratio (OR) = 1.89, 95% confidence interval (CI) = 1.14 to 3.12) and lower 90-day mortality (OR = 0.56, 95% CI = 0.32 to 1.00). The aspirin group had lower NIHSS scores on day 1 (β = −1.5, 95% CI = −2.8 to −0.27). The sICH rate was not significantly different between the groups (OR = 0.92, 95% CI = 0.60 to 1.43).

Conclusions:

Pre-stroke low-dose aspirin was associated with improved functional outcomes and reduced mortality in patients with DMVO undergoing MT, without a significant increase in sICH. These findings suggest that low-dose aspirin may be safe and associated with more frequent excellent outcomes for this patient population. Further prospective studies are needed to validate these results and assess long-term outcomes.

Keywords

Acute ischemic stroke distal medium vessel occlusions mechanical thrombectomy aspirin

Introduction

Acute ischemic stroke (AIS) is a significant contributor to global disability and mortality. A notable portion of AIS cases is due to distal medium vessel occlusion (DMVO), estimated to be 25–40%.^1
–14 Traditionally, intravenous thrombolysis (IVT) has been the primary treatment for AIS caused by DMVO.^15,16 However, advancements in endovascular techniques have led to an increased focus on mechanical thrombectomy (MT) as an alternative treatment option. This shift is supported by several observational studies and ongoing randomized controlled trials (RCTs) investigating the potential benefits of MT for select DMVO patients.^15,17
–30

Aspirin, a widely used antiplatelet medication, has shown effectiveness in preventing thrombotic events during neurointerventional procedures.^31
–33 Given that thromboembolic events are a primary mechanism of AIS, the impact of aspirin during MT in patients with DMVO remains unclear. While aspirin’s antiplatelet and anti-inflammatory properties may reduce these risks and provide neuroprotective benefits, these potential beneficial effects may be offset by an increased risk of hemorrhagic complications. Thus, a careful evaluation of the presumed safety and efficacy of MT in DMVO patients treated with aspirin is necessary^34
–36

Although many antiplatelet agents are used in cardiovascular disease prevention, whether as primary, secondary, or tertiary stage, low-dose aspirin remains the most widely used, particularly for primary prevention.^37,38

Data regarding the efficacy and safety of MT in patients who were taking aspirin before stroke onset are scarce.³⁹ While studies have reported the feasibility of MT in patients on aspirin with large vessel occlusion stroke,^40
–46 none has evaluated this in DMVO. In this study, we aim to evaluate the efficacy and safety of pre-stroke low-dose aspirin in DMVO stroke patients undergoing MT.

Methods

Our study is an analysis performed within the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry.^{17,36,47
–59} This article adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.^60,61

Ethical considerations and study approval

The institutional review board or local ethical standards committee at each of the 37 participating sites across North America, Asia, and Europe granted approval for this study. Due to the study’s retrospective nature, informed consent was waived. All data from this study’s findings are available from the corresponding author upon reasonable request.

Study population and inclusion criteria

We focused on patients with AIS due to DMVO as previously described.^17,47,54,55 Inclusion criteria were as follows: (1) AIS patients with DMVO in the M2, M3, and M4 segments of the middle cerebral artery (MCA) defined according to Saver et al.’s¹⁵ criteria and (2) those undergoing MT with or without IVT. Exclusion criteria were as follows: (1) patients with incomplete antiplatelet data, taking antiplatelet agents other than aspirin (e.g. clopidogrel, cilostazol), or taking aspirin at a dosage higher than 100 mg; (2) patients with M2 segments classified as dominant or large vessel occlusion (LVO); and (3) patients treated exclusively with intra-arterial thrombolytic agents.

Data collection process

Data collection involved consecutive patients from September 2017 to July 2023. Local neurointerventionalists or vascular neurologists assessed angiographic treatment success before forwarding data to the MAD-MT consortium. Each center self-reported these data.

We recorded comprehensive baseline clinical and demographic characteristics, including sex, age, hypertension, hypercholesterolemia, diabetes mellitus, atrial fibrillation, and smoking status. Furthermore, we documented the pre-stroke modified Rankin Scale (mRS) score, the occluded vessel, and National Institutes of Health Stroke Scale (NIHSS) score at presentation. In addition, patients were stratified into subgroups based on their occlusion location during the initial angiography, differentiating between medium (M2) and distal branches (M3, M4) of the MCA.

Additional data of interest encompassed antiplatelet and anticoagulation medication status. Patients were classified as being on antiplatelet therapy if they were taking any home antiplatelet medications (e.g. aspirin, clopidogrel, prasugrel, cilostazol) upon presentation. Similarly, patients were considered anticoagulated if they were on home vitamin K antagonists or direct oral anticoagulants at the time of presentation. Moreover, time from symptom onset to arterial puncture and recanalization, anesthesia type, access site (femoral or radial), and post-MT imaging modalities (computed tomography (CT), magnetic resonance (MR), or none) were recorded.

Procedural and technical details

Treatment consisted of MT alone or IVT + MT. MT access site was at the individual operator’s discretion. Similarly, the technique (aspiration, stent retriever, or combination) and number of passes were left to the treating physician’s discretion.

For patients in the combined MT + IVT group, IVT was given as per institutional protocol, using either alteplase or tenecteplase as per standard clinical guidelines. Alteplase was given at a standard dose of 0.9 mg/kg, with 10% of the total dose delivered as an initial bolus followed by an infusion of the remaining 90% over 60 min. Tenecteplase was administered in a single intravenous bolus at a dose of 0.25 mg/kg, infused over 5–10 s.

Outcomes

The primary outcome was functional independence at 90 days (mRS, 0–2), with secondary outcomes including excellent outcome at 90 days (mRS, 0–1), mortality (mRS, 6), and day 1 post-MT NIHSS score. Safety outcomes were hemorrhagic complications of any type and symptomatic intracerebral hemorrhage (sICH), defined according to “The Heidelberg Bleeding Classification.”⁶²

Statistical analysis

We employed inverse probability of treatment weighting (IPTW) to balance the distribution of confounding variables between the MT and medical management (MM) groups. The selection of propensity score (PS) weights over a regression-based, covariate-adjustment technique such as logistic regression was influenced by several considerations. To minimize residual confounding in observational studies,⁶³ a large number of variables can be summarized using PS techniques. Furthermore, notable variations were seen in the distribution of specific baseline features among the two groups. In addition, propensity score weights serve to mitigate the potential for bias by estimating scores in a manner that is independent of the outcome.⁶⁴

The estimation of PS weights was conducted using generalized boosted modeling (GBM) methodology. GBM is a machine learning multivariate non-parametric regression technique that estimates the PS of individuals iteratively to maximize balance in observed covariables.^65,66 GBM has the capability to integrate interactions among numerous factors, hence mitigating the potential for model misspecification.^66,67 Prior studies have demonstrated that GBM provides superior performance compared to logistic regression in PS estimation.⁶⁸ The current analyses utilized GBM as a method to mitigate the potential bias in results that may arise due to model misspecification.⁶⁵ The model included sex, age, hypercholesterolemia, occlusion location, hypertension, diabetes mellitus, atrial fibrillation presence, IVT, baseline NIHSS scores, pre-stroke mRS scores, pre-stroke use of anticoagulants, Alberta Stroke Program Early CT Score (ASPECTS), and stroke onset to puncture time, with the aim of estimating the average treatment effect (ATE). The mean Kolmogorov–Smirnov (KS.mean) statistic was employed as a stopping criterion for assessing and summarizing balance across pretreatment variables. A 10,000-tree GBM model with an interaction depth of 3, a shrinkage value of 0.01, and a bag fraction of 1 was utilized.

The analyses used balance diagnostics for PS weights, as per known practices.⁶⁹ The diagnostic analysis primarily examined the absolute standardized mean difference (ASMD) between weighted and unweighted variables. In our analysis, we deemed any ASMD greater than 0.10 to indicate covariate imbalance. The literature has proposed that any value equal to or below 0.10 can be considered as a trivial difference in terms of relative balance.^70,71 To minimize the mean square error a doubly robust estimation was employed, wherein additional adjustments were made for the covariates using weighted multivariable logistic regression analysis.^65,72 All statistical analyses were performed using R Studio Version 4.2.2. No imputations were made, and adjustments for multiple testing were not performed.

Results

Patient demographics and baseline characteristics

A total of 1354 patients were included in the study (median age 74 years; interquartile range (IQR), 62–82, 638 males, 715 females), with 1204 patients not on antiplatelet therapy and 150 patients on low-dose aspirin. Table 1 provides a summary of baseline characteristics.

Table 1.

Baseline characteristics.

Variable	Overall	No antiplatelet	Aspirin (75–100 mg)	p^a
Variable	N = 1354	N = 1204	N = 150	p^a
Male, n (%)	638 (47)	562 (47)	76 (51)	0.36
Age, median (IQR)	74 (62, 82)	74 (62, 82)	75 (68, 82)	0.1
Hypercholesterolemia, n (%)	399 (30)	316 (27)	83 (55)	<0.001
Hypertension, n (%)	875 (65)	773 (64)	102 (68)	0.37
Site of initial occlusion, n (%)				0.26
Medium (M2)	1177 (87)	1051 (87)	126 (84)
Distal (M3, M4)	177 (13)	153 (13)	24 (16)
Diabetes, n (%)	279 (21)	241 (20)	38 (25)	0.13
Atrial fibrillation, n (%)	492 (36)	432 (36)	60 (40)	0.33
Current smokers, n (%)	193 (14)	157 (13)	36 (24)	<0.001
Previous use of antiplatelet drugs, n (%)	150 (11)	0 (0)	150 (100)	<0.001
Previous use of anticoagulant drugs, n (%)	342 (27)	315 (28)	27 (18)	0.012
Pre-stroke mRS, n (%)				0.6
0	861 (67)	753 (66)	108 (72)
1	161 (13)	145 (13)	16 (11)
2	109 (8.5)	100 (8.8)	9 (6.0)
3	108 (8.4)	95 (8.4)	13 (8.7)
4	46 (3.6)	42 (3.7)	4 (2.7)
ASPECTS, median (IQR)	9.00 (8.00, 10.00)	9.00 (8.00, 10.00)	8.00 (7.00, 10.00)	0.002
Baseline NIHSS, median (IQR)	10 (6, 17)	10 (6, 17)	9 (5, 17)	0.31

mRS: modified Rankin Scale; NIHSS: National Institutes of Health Stroke Scale; ASPECTS: Alberta Stroke Program Early CT Score.

Pearson’s chi-square test; Wilcoxon rank-sum test; Fisher’s exact test.

Notable differences were observed in the prevalence of hypercholesterolemia (27% in no antiplatelet vs 55% in aspirin group, p < 0.001) and current smokers (13% in no antiplatelet vs 24% in aspirin group, p < 0.001). Previous use of anticoagulant drugs was higher in the no antiplatelet group (28% vs 18%, p = 0.012). The median ASPECTS was slightly lower in the aspirin group (8.00, IQR, 7.00–10.00) compared to the no antiplatelet group (9.00, IQR, 8.00–10.00, p = 0.002). Other baseline characteristics, including hypertension, diabetes, atrial fibrillation, and baseline NIHSS scores, showed no significant differences between the groups. Balance diagnostics for various patient characteristics after propensity score weighting are presented in Supplementary Table 1.

Periprocedural details

Supplementary Table 2 presents the periprocedural details. The administration of IVT was comparable between the groups (45% in the aspirin group vs 47% in the no antiplatelet group; p = 0.78). A significant difference was observed in the first-line technique used, with a higher proportion of aspiration techniques in the aspirin group (24% vs 18% in the no antiplatelet group; p = 0.002).

The median onset to arterial puncture time was shorter in the aspirin group (230 min, IQR, 154–379) compared to the no antiplatelet group (270 min, IQR, 180–442; p = 0.007). Similarly, the median onset to recanalization time was shorter in the aspirin group (294 min, IQR, 193–440) compared to the no antiplatelet group (330 min, IQR, 231–514; p = 0.006). The use of general anesthesia was more common in the aspirin group (58% vs 26%; p < 0.001).

Outcomes

Supplementary Table 3 shows the outcomes of the univariable crude analysis and the doubly robust IPTW evaluation. The 90-day mRS 0–2 was better in the aspirin group (mRS 0–2: IPTW model odds ratio (OR) = 1.89, 95% confidence interval (CI), 1.14 to 3.12, p = 0.013). Although the proportion of patients achieving mRS 0–1 was higher in the aspirin group, the difference between the two groups was not statistically significant (mRS 0–1: IPTW model OR = 1.62, 95% CI, 0.98 to 2.67, p = 0.06). Patients in the aspirin group had a significantly lower NIHSS score on day 1 (median 4, IQR, 2–12) compared to the no antiplatelet group (median 6, IQR, 2–14, crude analysis: β = −2.2, [95% CI, −3.9 to −0.55], p = 0.009; IPTW model: β = −1.5, [95% CI, −2.8 to −0.27], p = 0.018). However, there were no significant differences in the rates of thrombolysis in cerebral infarction (TICI) 2b-3 and TICI 2c-3 between the groups.

Mortality at 90 days was lower in the aspirin group (13% vs 17% in no antiplatelet, IPTW model OR = 0.56, 95% CI, 0.32 to 1.00, p = 0.048). The aspirin group also had a lower incidence of HI1 type ICH (IPTW model OR = 0.12, 95% CI, 0.05 to 0.31, p < 0.001) and a higher incidence of PH2 type ICH (IPTW model OR = 5.80, 95% CI, 2.43 to 13.8, p < 0.001). The rates of HI2, PH1, and subarachnoid hemorrhage (SAH) were not statistically significant between the comparable groups.

Discussion

In this multicenter multinational study, we examined a total of 1354 MCA DMVO stroke patients, comparing MT outcomes between those on low-dose aspirin and no antiplatelet therapy. Pre-stroke low-dose aspirin use was significantly associated with higher functional independence (mRS, 0–2), lower day 1 post-MT NIHSS scores at follow-up, and a reduced mortality rate at 90 days without significant increase in the rate of sICH.

Aspirin use in the primary prevention of cardiovascular disease has been shown to decrease all-cause mortality, including major cardiovascular complications such as myocardial infarction and ischemic stroke. However, it simultaneously increases the risk of hemorrhagic stroke and bleeding.^38,73,74 Daily aspirin use (160–300 mg) started within the first 48 h of ischemic stroke symptom onset is associated with reduced morbidity and mortality.⁷⁵

Aspirin enhances circulation by preventing platelet aggregation, the initial step in thrombus formation, through the irreversible inhibition of COX-1 and COX-2 via acetylation.⁷⁶ This is particularly relevant in DMVO strokes, where many studies suggest that thrombi in distal occlusions have different compositions, being RBC-rich, fresher, less compact, and more responsive to treatment,⁷⁷ in contrast to the fibrin-rich thrombi of atherosclerotic plaque origin, which are mostly responsible for more proximal occlusions. In addition, the structural differences between large and medium-sized arteries play a role. Large arteries have a thicker tunica media and a slightly thicker tunica adventitia.⁷⁸ The tunica media, composed of smooth muscles controlled by the sympathetic and parasympathetic nervous systems, contracts in response to ischemic stroke, leading to vasoconstriction and reducing the effectiveness of antiplatelet therapy in preventing artery occlusion by thrombus compared to medium vessels.^62,79 Nonetheless, further research is necessary to confirm this phenomenon.

Many studies on the safety of using aspirin during IVT have demonstrated an increased risk of bleeding and mortality.⁷⁵ However, a recent retrospective study conducted in the United Kingdom showed contradictory results, suggesting that intravenous aspirin during emergent MT is associated with good clinical outcomes and does not increase the risk of ICH, even when combined with IVT.⁸⁰ Our results align with a Chinese observational study that showed better clinical outcomes in patients taking single or dual antiplatelet therapy than no antiplatelet therapy.⁸¹ However, contradictory results were observed in a nationwide prospective study, which showed no improvement in clinical outcomes and functional independence with antiplatelet monotherapy before MT.³⁹ The improved functional outcomes in our cohort’s low-dose aspirin group may be due to the type of vessels studied. While the nationwide study focused on LVOs, our research was confined to DMVOs.

Furthermore, our results contradicted another study, MR CLEAN, which found no evidence of better functional outcomes in patients with baseline antiplatelet therapy before MT for LVO.⁸² This can be explained by the fact that the previous studies were conducted on patients with baseline antiplatelet therapy in general, regardless of the type, and did not focus on the specific use of any one type.^39,82 However, our study focused only on using low-dose aspirin as the baseline antiplatelet and on MT for DMVO.

Our findings indicate that while the rate of some ICH subtypes in the aspirin group were higher, most hemorrhages were asymptomatic. This observation is supported by the lack of significant difference in the occurrence of sICH between the two cohorts. Although patients on aspirin had a lower incidence of HI type 1 ICH, they had a higher incidence of PH2 type ICH. These results are conflict with the MR CLEAN study, which showed a significant increase in the risk of ICH in patients on baseline antiplatelet therapy after MT.⁸² This discrepancy may be explained by the fact that the no antiplatelet group had a slightly higher percentage of previous anticoagulant use, which may increase the risk of sICH. However, our results are consistent with the findings of the nationwide study,³⁹ the Chinese study,⁸¹ and the two smaller studies,^82,83 where no significant increase in ICH risk was observed.

Our findings suggest that MT is safe in patients taking pre-stroke aspirin, with improved outcomes among patients taking aspirin seeming to be more pronounced in DMVO compared to LVO. However, further validation via prospective studies is needed.

Our study has multiple strengths, including large-scale, multinational, multicenter, and real-world data, thereby improving generalizability. However, our study is not without limitations. The primary limitation is that the indication for baseline aspirin use was not recorded. Nonetheless, the exact reason for aspirin use may have a limited impact on our findings as our focus was on the safety of performing MT in patients already on aspirin, irrespective of its initial indication, rather than on the indication for prescribing aspirin before MT. Future studies should consider recording the baseline indication to assess its potential contribution to outcomes.

Other limitations include, first, the retrospective nature of the analysis introduces the possibility of selection bias, potentially influencing the generalizability of the findings. Second, the scope of the study is limited to a 90-day post-intervention follow-up period, which restricts our insight into the long-term repercussions of MT complications on patients’ functional recovery and overall quality of life. Third, we did not include patients who had higher aspirin dose prior to MT, so we do not know if our results are generalizable to this subgroup of patients. Finally, the exact cause of stroke was not documented, which limits our ability to draw conclusions about the underlying etiology.

Conclusion

In conclusion, our findings suggest that MT for DMVOs is safe for patients with pre-stroke low-dose aspirin use. This association with improved functional outcomes and reduced mortality, without a significant increase in sICH, highlights aspirin’s potential role in enhancing treatment efficacy. However, caution is warranted, as pre-stroke aspirin is linked to a higher incidence of PH2-type ICH. Further prospective studies are needed to validate these results and explore the long-term effects of aspirin use in this patient population.

Supplemental Material

sj-docx-1-wso-10.1177_17474930251317883 – Supplemental material for Efficacy and safety of mechanical thrombectomy in distal medium middle cerebral artery occlusion ischemic stroke patients on low-dose aspirin

Supplemental material, sj-docx-1-wso-10.1177_17474930251317883 for Efficacy and safety of mechanical thrombectomy in distal medium middle cerebral artery occlusion ischemic stroke patients on low-dose aspirin by Hamza Adel Salim, Vivek Yedavalli, Fathi Milhem, Basel Musmar, Nimer Adeeb, Motaz Daraghma, Kareem El Naamani, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kühn, Jane Khalife, Sherief Ghozy, Luca Scarcia, Benjamin YQ Tan, Robert W Regenhardt, Jeremy J Heit, Nicole M Cancelliere, Joshua D Bernstock, Aymeric Rouchaud, Jens Fiehler, Sunil Sheth, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Mohamad Abdalkader, Piers Klein, Thomas R Marotta, Julian Spears, Takahiro Ota, Ashkan Mowla, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, James E Siegler, Thanh N Nguyen, Ricardo Varela, Amanda Baker, Muhammed Amir Essibayi, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Constantin Hecker, Hamza Shaikh, Christoph J Griessenauer, David S Liebeskind, Alessandro Pedicelli, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Erwah Kalsoum, Max Wintermark, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Adrien Guenego and Adam A Dmytriw in International Journal of Stroke

Supplemental Material

sj-docx-2-wso-10.1177_17474930251317883 – Supplemental material for Efficacy and safety of mechanical thrombectomy in distal medium middle cerebral artery occlusion ischemic stroke patients on low-dose aspirin

Supplemental material, sj-docx-2-wso-10.1177_17474930251317883 for Efficacy and safety of mechanical thrombectomy in distal medium middle cerebral artery occlusion ischemic stroke patients on low-dose aspirin by Hamza Adel Salim, Vivek Yedavalli, Fathi Milhem, Basel Musmar, Nimer Adeeb, Motaz Daraghma, Kareem El Naamani, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kühn, Jane Khalife, Sherief Ghozy, Luca Scarcia, Benjamin YQ Tan, Robert W Regenhardt, Jeremy J Heit, Nicole M Cancelliere, Joshua D Bernstock, Aymeric Rouchaud, Jens Fiehler, Sunil Sheth, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Mohamad Abdalkader, Piers Klein, Thomas R Marotta, Julian Spears, Takahiro Ota, Ashkan Mowla, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, James E Siegler, Thanh N Nguyen, Ricardo Varela, Amanda Baker, Muhammed Amir Essibayi, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Constantin Hecker, Hamza Shaikh, Christoph J Griessenauer, David S Liebeskind, Alessandro Pedicelli, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Erwah Kalsoum, Max Wintermark, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Adrien Guenego and Adam A Dmytriw in International Journal of Stroke

Supplemental Material

sj-docx-3-wso-10.1177_17474930251317883 – Supplemental material for Efficacy and safety of mechanical thrombectomy in distal medium middle cerebral artery occlusion ischemic stroke patients on low-dose aspirin

Supplemental material, sj-docx-3-wso-10.1177_17474930251317883 for Efficacy and safety of mechanical thrombectomy in distal medium middle cerebral artery occlusion ischemic stroke patients on low-dose aspirin by Hamza Adel Salim, Vivek Yedavalli, Fathi Milhem, Basel Musmar, Nimer Adeeb, Motaz Daraghma, Kareem El Naamani, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kühn, Jane Khalife, Sherief Ghozy, Luca Scarcia, Benjamin YQ Tan, Robert W Regenhardt, Jeremy J Heit, Nicole M Cancelliere, Joshua D Bernstock, Aymeric Rouchaud, Jens Fiehler, Sunil Sheth, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Mohamad Abdalkader, Piers Klein, Thomas R Marotta, Julian Spears, Takahiro Ota, Ashkan Mowla, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, James E Siegler, Thanh N Nguyen, Ricardo Varela, Amanda Baker, Muhammed Amir Essibayi, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Constantin Hecker, Hamza Shaikh, Christoph J Griessenauer, David S Liebeskind, Alessandro Pedicelli, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Erwah Kalsoum, Max Wintermark, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Adrien Guenego and Adam A Dmytriw in International Journal of Stroke

Footnotes

Declaration of conflicting interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation. Dr Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work. Dr Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading), and Artedrone (Board); all not directly related to the present work. Dr Henninger received support from NINDS NS131756, NINR NR020231, and NINDS NS113844 during the conduct of the study. All unrelated to the present work. Dr Liebeskind is consultant for Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, and Rapid Medical. Dr Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra. Dr Nguyen reports Associate Editor of Stroke; advisory board of Brainomix, Aruna Bio. Dr Puri is a consultant for Medtronic Neurovascular, Stryker Neurovascular, Balt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc, and Arsenal Medical; he received research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular, and Stryker Neurovascular and holds stocks in InNeuroCo, Agile, Perfuze, Galaxy, and NTI. Dr Jabbour is a consultant for Medtronic, Microvention, and Cerus. Dr Siegler has served as a consultant for AstraZeneca and has received funding from the National Institutes of Health (R61NS135583), Viz.ai, Philips, and Medtronic.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Hamza Adel Salim

Vivek Yedavalli

Nils Henninger

Benjamin YQ Tan

Nicole M Cancelliere

Răzvan Alexandru Radu

Takahiro Ota

Pascal Jabbour

Frédéric Clarençon

James E Siegler

Thanh N Nguyen

Muhammed Amir Essibayi

Nestor R Gonzalez

Alessandro Pedicelli

Andrea M Alexandre

Tobias D Faizy

Adrien Guenego

Adam A Dmytriw

Supplemental material

Supplemental material for this article is available online.

References

Mei

Salim

Lakhani

, et al. Lower admission stroke severity is associated with good collateral status in distal medium vessel occlusion stroke. J Neuroimaging 2024; 34: 424–429.

Rehman

Nadeem

Kasi

ABU

, et al. Role of hypoperfusion intensity ratio in vessel occlusions: a review on safety and clinical outcomes. AJNR Am J Neuroradiol 2024; 46: 1069–1081.

Yedavalli

Salim

Mei

, et al. Decreased quantitative cerebral blood volume is associated with poor outcomes in large core patients. Stroke 2024; 55: 2409–2419.

Lakhani

Balar

Salim

, et al. CT perfusion derived rCBV < 42% lesion volume is independently associated with follow-up FLAIR infarct volume in anterior circulation large vessel occlusion. Diagnostics (Basel) 2024; 14: 845.

Salim

Hamam

Parilday

, et al. Relative cerebral blood flow as an indirect imaging surrogate in patients with anterior circulation large vessel occlusion and association of baseline characteristics with poor collateral status. J Am Heart Assoc 2024; 13: e034581.

Yedavalli

Kihira

Shahrouki

, et al. CTP-based estimated ischemic core: a comparative multicenter study between Olea and RAPID software. J Stroke Cerebrovasc Dis 2023; 32: 107297.

Salim

Vagal

Lakhani

, et al. Association of pretreatment perfusion imaging parameters with 90-day excellent functional outcomes in anterior circulation distal medium vessel occlusion stroke. AJNR Am J Neuroradiol 2024; 46: 892–899.

Mei

Salim

Lakhani

, et al. Prolonged venous transit is associated with worse neurological recovery in successfully reperfused large vessel strokes. Ann Clin Transl Neurol 2024; 12: 26–33.

Lakhani

Balar

Vagal

, et al. CT perfusion derived relative cerebral blood volume < 42 % is negatively associated with poor functional outcomes at discharge in anterior circulation large vessel occlusion stroke. J Clin Neurosci 2024; 130: 110907.

10.

Yedavalli

Adel Salim

Lakhani

, et al. Mismatch vs no mismatch in large core—a matter of definition. Clin Neuroradiol 2024; 35: 165–172.

11.

Salim

Huang

Lakhani

, et al. Perfusion imaging predicts short-term clinical outcome in isolated posterior cerebral artery occlusion stroke. Journal of Neuroimaging 2024; 34: 766–772.

12.

Salim

Lakhani

Mei

, et al. Prolonged venous transit is associated with lower odds of excellent recovery after reperfusion in anterior large-vessel occlusion stroke. Eur J Neurol 2025; 32: e16563.

13.

Cho

Lakhani

Balar

, et al. AM-PAC 6-clicks basic mobility and daily activities scores predict 90-day modified Rankin score in patients with acute ischemic stroke secondary to large vessel occlusion. J Clin Med 2024; 13: 7119.

14.

Koneru

Mei

Lakhani

, et al. Prolonged venous transit on perfusion imaging is associated with longer lengths of stay in acute large vessel occlusions. Am J Neuroradiol 2024; 46: 887–891.

15.

Saver

Chapot

Agid

, et al. Thrombectomy for distal, medium vessel occlusions: a consensus statement on present knowledge and promising directions. Stroke 2020; 51: 2872–2884.

16.

Mowla

Memon

Razavi

, et al. Safety of intravenous thrombolysis for acute ischemic stroke in patients taking warfarin with subtherapeutic INR. J Stroke Cerebrovasc Dis 2021; 30: 105678.

17.

Siegler

Shaikh

Khalife

, et al. Aspiration versus stent-retriever as first-line endovascular therapy technique for primary medium and distal intracranial occlusions: a propensity-score matched multicenter analysis. Stroke 2023; 3: e000931.

18.

Ozkara

Karabacak

Kotha

, et al. Development of machine learning models for predicting outcome in patients with distal medium vessel occlusions: a retrospective study. Quant Imaging Med Surg 2023; 13: 5815–5830.

19.

Farouki

Bonnet

Mine

, et al. First-pass effect predicts clinical outcome and infarct growth after thrombectomy for distal medium vessel occlusions. Neurosurgery 2022; 91: 913–919.

20.

Gory

Lapergue

Blanc

, et al. Contact aspiration versus stent retriever in patients with acute ischemic stroke with M2 occlusion in the ASTER randomized trial (contact aspiration versus stent retriever for successful revascularization). Stroke 2018; 49: 461–464.

21.

Menon

Hill

Davalos

, et al. Efficacy of endovascular thrombectomy in patients with M2 segment middle cerebral artery occlusions: meta-analysis of data from the HERMES Collaboration. J Neurointerv Surg 2019; 11: 1065–1069.

22.

Grossberg

Rebello

Haussen

, et al. Beyond large vessel occlusion strokes: distal occlusion thrombectomy. Stroke 2018; 49: 1662–1668.

23.

Barchetti

Cagnazzo

Raz

Barbagallo

Toccaceli

Peschillo

Mechanical thrombectomy of distal occlusions using a direct aspiration first pass technique compared with new generation of mini-0.017 microcatheter compatible-stent retrievers: a meta-analysis. World Neurosurg 2020; 134: 111–119.

24.

Waqas

Kuo

Dossani

, et al. Mechanical thrombectomy versus intravenous thrombolysis for distal large-vessel occlusion: a systematic review and meta-analysis of observational studies. Neurosurg Focus 2021; 51: E5.

25.

Bilgin

Hardy

Hutchison

, et al. First-line thrombectomy strategy for distal and medium vessel occlusions: a systematic review. J Neurointerv Surg 2023; 15: 539–546.

26.

Loh

EDW

Toh

KZX

Kwok

GYR

, et al. Endovascular therapy for acute ischemic stroke with distal medium vessel occlusion: a systematic review and meta-analysis. J Neurointerv Surg 2023; 15: e452–e459.

27.

Rodriguez-Calienes

Vivanco-Suarez

Sequeiros

, et al. Mechanical thrombectomy for the treatment of primary and secondary distal medium-vessel occlusion stroke: systematic review and meta-analysis. J Neurointerv Surg 2023; 15: e460–e467.

28.

Toh

KZX

Koh

Loh

, et al. Distal medium vessel occlusions in acute ischaemic stroke—stent retriever versus direct aspiration: a systematic review and meta-analysis. Eur Stroke J 2023; 8: 434–447.

29.

Strambo

Michel

Nguyen

, et al. Endovascular versus medical therapy in posterior cerebral artery stroke: role of baseline NIHSS score and occlusion site. Stroke 2024; 55: 1787–1797.

30.

Räty

Nguyen

Nagel

, et al. Endovascular thrombectomy versus intravenous thrombolysis of posterior cerebral artery occlusion stroke. J Stroke 2024; 26: 290–299.

31.

Lee

Gagnidze

Pan

, et al. Preoperative low-dose aspirin exposure and outcomes after emergency neurosurgery for traumatic intracranial hemorrhage in elderly patients. Anesth Analg 2017; 125: 514–520.

32.

Cuellar

Petrizzo

Vaswani

, et al. Does aspirin administration increase perioperative morbidity in patients with cardiac stents undergoing spinal surgery? Spine (Phila Pa 1976) 2015; 40: 629–635.

33.

Shi

Zhao

, et al. Effects and safety of aspirin use in patients after cerebrovascular bypass procedures. Stroke Vasc Neurol 2021; 6: 624–630.

34.

Feng

Chen

Sun

Aspirin exerts neuroprotective effects by reversing lipopolysaccharide-induced secondary brain injury and inhibiting matrix metalloproteinase-3 gene expression. Dis Markers 2021; 2021: 3682034.

35.

Salim

Musmar

Saifi

, et al. The impact of polypill on adherence and cardiovascular outcomes: a comprehensive systematic review with meta-analysis. Curr Cardiol Rev 2024; 20: 61–71.

36.

Yedavalli

Salim

Musmar

, et al. Symptomatic intracerebral hemorrhage in proximal and distal medium middle cerebral artery occlusion patients treated with mechanical thrombectomy. J Neurointerv Surg. https://jnis.bmj.com/content/early/2024/07/08/jnis-2024-021879 (2024, accessed 11 July 2024).

37.

Cofer

Barrett

Berger

JS.

Aspirin for the primary prevention of cardiovascular disease: time for a platelet-guided approach. Arterioscler Thromb Vasc Biol 2022; 42: 1207–1216.

38.

Raju

Sobieraj-Teague

Hirsh

, et al. Effect of aspirin on mortality in the primary prevention of cardiovascular disease. Am J Med 2011; 124: 621–629.

39.

Klail

Sedova

Vinklarek

, et al. Safety and efficacy of baseline antiplatelet treatment in patients undergoing mechanical thrombectomy for ischemic stroke: antiplatelets before mechanical thrombectomy. J Vasc Interv Radiol 2023; 34: 1502–1510.

40.

Purrucker

Wolf

Haas

, et al. Safety of endovascular thrombectomy in patients receiving non-vitamin K antagonist oral anticoagulants. Stroke 2016; 47: 1127–1130.

41.

Xian

Federspiel

Hernandez

, et al. Use of intravenous recombinant tissue plasminogen activator in patients with acute ischemic stroke who take non-vitamin K antagonist oral anticoagulants before stroke. Circulation 2017; 135: 1024–1035.

42.

Mundiyanapurath

Tillmann

Möhlenbruch

Bendszus

Ringleb

PA.

Endovascular stroke therapy may be safe in patients with elevated international normalized ratio. J Neurointerv Surg 2017; 9: 1187–1190.

43.

Benavente

Larrosa

García-Cabo

, et al. Safety and efficacy of mechanical thrombectomy in acute ischemic stroke of anticoagulated patients—a prospective observational study. J Stroke Cerebrovasc Dis 2016; 25: 2093–2098.

44.

Alonso de Leciñana

Fuentes

Ximénez-Carrillo

, et al. A collaborative system for endovascular treatment of acute ischaemic stroke: the Madrid Stroke Network experience. Eur J Neurol 2016; 23: 297–303.

45.

Fuentes

Alonso de Leciñana

Ximénez-Carrillo

, et al. Futile interhospital transfer for endovascular treatment in acute ischemic stroke: the Madrid stroke network experience. Stroke 2015; 46: 2156–2161.

46.

Chen

J-H

Hong

C-T

Chung

C-C

, et al. Safety and efficacy of endovascular thrombectomy in acute ischemic stroke treated with anticoagulants: a systematic review and meta-analysis. Thromb J 2022; 20: 35.

47.

Salim

Musmar

Adeeb

, et al. Outcomes of mechanical thrombectomy in anticoagulated patients with acute distal and medium vessel stroke. Eur Stroke J 2024; 9: 896–906.

48.

Salim

Yedavalli

Musmar

, et al. Endovascular therapy versus best medical management in distal medium middle cerebral artery acute ischaemic stroke: a multinational multicentre propensity score-matched study. J Neurol Neurosurg Psychiatry. Epub ahead of print 23 July 2024. DOI: 10.1136/jnnp-2024-333669.

49.

Salim

Lakhani

Balar

, et al. Follow-up infarct volume on fluid attenuated inversion recovery (FLAIR) imaging in distal medium vessel occlusions: the role of cerebral blood volume index. J Neurol 2024; 271: 3389–3397.

50.

Salim

Yedavalli

Musmar

, et al. Mechanical thrombectomy versus intravenous thrombolysis in distal medium vessel acute ischemic stroke: a multinational multicenter propensity score-matched study. J Stroke 2024; 26: 434–445.

51.

Yedavalli

Salim

Musmar

, et al. Pretreatment predictors of very poor clinical outcomes in medium vessel occlusion stroke patients treated with mechanical thrombectomy. Int J Stroke 2024; 19: 1123–1133.

52.

Salim

Pulli

Yedavalli

, et al. Endovascular therapy versus medical management in isolated posterior cerebral artery acute ischemic stroke: a multinational multicenter propensity score-weighted study. Eur Stroke J 2024; 10: 387–396.

53.

Salim

Pulli

Yedavalli

, et al. Endovascular therapy versus medical management in isolated anterior cerebral artery acute ischemic stroke: a multinational multicenter propensity score-weighted study. J Neurointerv Surg 2024; 17: (e2):e356–e364.

54.

Radu

Costalat

Fahed

, et al. First pass effect as an independent predictor of functional outcomes in medium vessel occlusions: an analysis of an international multicenter study. Eur Stroke J 2027; 9: 114–123.

55.

Dmytriw

Musmar

Salim

, et al. Incidence and clinical outcomes of perforations during mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke: a retrospective, multicenter, and multinational study. Eur Stroke J 2024; 9: 328–337.

56.

Radu

Costalat

Romoli

, et al. Outcomes with general anesthesia compared to conscious sedation for endovascular treatment of medium vessel occlusions: results of an international multicentric study. Clin Neuroradiol 2024; 34: 761–769.

57.

Kühn

Puri

Salim

, et al. Multicenter evaluation of mechanical thrombectomy for distal medium vessel occlusions with National Institute of Health Stroke Scale Scores ⩾ 6 and ⩽ 6. J Neurol 2024; 271: 5853–5863.

58.

Dmytriw

Ghozy

Salim

, et al. Assessment of thrombectomy versus combined thrombolysis and thrombectomy in patients with acute ischemic stroke and medium vessel occlusion. Radiology 2024; 312: e233041.

59.

Yedavalli

Salim

Musmar

, et al. Predictors and outcomes of excellent recanalization versus successful recanalization after thrombectomy in proximal and distal medium vessel occlusion strokes: a multinational study. Stroke 2024; 4: e001421.

60.

Cuschieri

The STROBE guidelines. Saudi J Anaesth 2019; 13: S31–S34.

61.

von Elm

Altman

Egger

, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med 2007; 4: e296.

62.

The Heidelberg Bleeding classification. Stroke. https://www.ahajournals.org/doi/10.1161/STROKEAHA.115.010049 (accessed 18 January 2024).

63.

Rothman

Greenland

Lash

TL.

Modern epidemiology. Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2008.

64.

Lopez

Foxe

Mao

Thompson

Martin

Freedman

EG.

Breastfeeding duration is associated with domain-specific improvements in cognitive performance in 9–10-year-old children. Front Public Health 2021; 9: 657422.

65.

McCaffrey

Griffin

Almirall

, et al. A tutorial on propensity score estimation for multiple treatments using generalized boosted models. Stat Med 2013; 32: 3388–3414.

66.

McCaffrey

Ridgeway

Morral

AR.

Propensity score estimation with boosted regression for evaluating causal effects in observational studies. Psychol Methods 2004; 9: 403–425.

67.

Parast

McCaffrey

Burgette

, et al. Optimizing variance-bias trade-off in the TWANG package for estimation of propensity scores. Health Serv Outcomes Res Methodol 2017; 17: 175–197.

68.

Lee

Lessler

Stuart

EA.

Improving propensity score weighting using machine learning. Stat Med 2010; 29: 337–346.

69.

Austin

Stuart

EA.

Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med 2015; 34: 3661–3679.

70.

Nguyen

T-L

Collins

Spence

, et al. Double-adjustment in propensity score matching analysis: choosing a threshold for considering residual imbalance. BMC Med Res Methodol 2017; 17: 78.

71.

Austin

PC.

An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res 2011; 46: 399–424.

72.

Hullsiek

Louis

TA.

Propensity score modeling strategies for the causal analysis of observational data. Biostatistics 2002; 3: 179–193.

73.

Dmytriw

Musmar

Salim

, et al. The impact of postoperative aspirin in patients undergoing Woven EndoBridge: a multicenter, institutional, propensity score-matched analysis. J Neurointerv Surg 2024; 17: (e1):e15–e24.

74.

Dmytriw

Salim

Musmar

, et al. Dual layer vs single layer Woven EndoBridge device in the treatment of intracranial aneurysms: a propensity score-matched analysis. Neurosurg Rev 2024; 47: 116.

75.

Park

Smith

Wanserski

, et al. Aspirin in patients with acute ischemic stroke. Am Fam Physician 2009; 79: 226–227.

76.

Wang

Xiong

Feng

Aspirin resistance and promoting blood circulation and removing blood stasis: current situation and prospectives. Evid Based Complement Alternat Med 2014; 2014: 954863.

77.

Pikija

Magdic

Trkulja

, et al. Intracranial thrombus morphology and composition undergoes time-dependent changes in acute ischemic stroke: a CT densitometry study. Int J Mol Sci 2016; 17: 1959.

78.

Artery—Structure, Function & Types. Britannica. https://www.britannica.com/science/artery (2024, accessed 9 July 2024).

79.

Balch

MHH

Nimjee

Rink

, et al. Beyond the brain: the systemic pathophysiological response to acute ischemic stroke. J Stroke 2020; 22: 159–172.

80.

Ingleton

Raseta

Chung

R-E

, et al. Is intraprocedural intravenous aspirin safe for patients who require emergent extracranial stenting during mechanical thrombectomy? Stroke Vasc Neurol 2024; 9: 279–288.

81.

Huo

Raynald

Jing

, et al. Safety and efficacy of oral antiplatelet for patients who had acute ischaemic stroke undergoing endovascular therapy. Stroke Vasc Neurol 2020; 6: 230–237.

82.

Mulder

Berkhemer

Fransen

, et al. Does prior antiplatelet treatment improve functional outcome after intra-arterial treatment for acute ischemic stroke? Int J Stroke 2017; 12: 368–376.

83.

Pandhi

Tsivgoulis

Krishnan

, et al. Antiplatelet pretreatment and outcomes following mechanical thrombectomy for emergent large vessel occlusion strokes. J Neurointerv Surg 2018; 10: 828–833.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.02 MB