The safety and efficacy of anti-thrombotic agents during mechanical thrombectomy procedure for acute ischemic stroke: A systematic review and meta-analysis

Luh Ari Devanita S; I Gede Raka Adhyatma; I Putu Ananta Wijaya Sabudi; Luh Nyoman Ari Trisnasanti

doi:10.7461/jcen.2026.E2025.11.006

J Cerebrovasc Endovasc Neurosurg > Epub ahead of print

Devanita S, Adhyatma, Sabudi, and Trisnasanti: The safety and efficacy of anti-thrombotic agents during mechanical thrombectomy procedure for acute ischemic stroke: A systematic review and meta-analysis

Review Article

Journal of Cerebrovascular and Endovascular Neurosurgery 2026;jcen.2026.E2025.11.006.

Published online: March 25, 2026

DOI: https://doi.org/10.7461/jcen.2026.E2025.11.006

The safety and efficacy of anti-thrombotic agents during mechanical thrombectomy procedure for acute ischemic stroke: A systematic review and meta-analysis

Luh Ari Devanita S¹

, I Gede Raka Adhyatma², I Putu Ananta Wijaya Sabudi³, Luh Nyoman Ari Trisnasanti⁴

¹General Practitioner, Bangli General Hospital, Bali, Indonesia

²Faculty of Medicine, Udayana University, Denpasar, Bali, Indonesia

³Department of Neurosurgery, Klungkung Regional Hospital, Bali, Indonesia

⁴Department of Neurology, Gema Santi Regional Hospital, Nusa Penida, Klungkung, Bali, Indonesia

Correspondence to Luh Ari Devanita S General Practitioner, Bangli General Hospital, Jl. Brigjen Ngurah Rai, Bangli, Bali, 80613 Indonesia Tel +6282144024483 E-mail devanitaari.dr@gmail.com

Received November 7, 2025 Revised January 31, 2026 Accepted February 17, 2026

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

Ischemic stroke, primarily driven by large-vessel atherosclerosis, is frequently treated with mechanical thrombectomy (MT). While anti-thrombotic agents during MT procedure are commonly used, their risk-benefit profile remains unclear. This study compares the safety and efficacy of anti-thrombotic administration in acute ischemic stroke patients undergoing MT.

Methods

We systematically searched PubMed, ScienceDirect, and Google Scholar for studies evaluating anti-thrombotic use during MT. Data were analyzed using Review Manager (Web Version). We calculated odds ratios (OR) with 95% confidence intervals (CI) for safety outcomes (sICH and 3- to 6-month mortality) and efficacy outcomes (successful recanalization and functional independence).

Results

Thirteen observational studies (n=4,923) were included. Anti-thrombotic use did not significantly alter the risk of sICH [OR 0.83 (95% CI 0.63-1.1); p=0.21; I2=25%]. However, it was associated with reduced 3-6-month mortality [OR 0.57 (95% CI 0.33-0.99); p=0.05; I2=86%], though heterogeneity was high. Regarding efficacy, anti-thrombotic use showed no significant association with successful recanalization [OR 1.22 (95% CI 0.81-1.83); p=0.63; I2=74%] or functional independence [OR 1.07 (95% CI 0.81-1.41); p=0.31; I2=73%].

Conclusions

Administration of anti-thrombotic agents during MT may reduce 3- to 6-month mortality without increasing sICH risk. However, they do not appear to significantly improve recanalization rates or functional independence. Given the high heterogeneity in mortality data, these results should be interpreted with caution.

Keywords: Acute ischemic stroke, Antithrombotic therapy, Treatment outcome, Mechanical thrombectomy, Mortality, Symptomatic intracranial hemorrhage

INTRODUCTION

Stroke remains a leading cause of global disability and the second leading cause of death. According to the World Stroke Organization’s 2022 Global Stroke Factsheet, the lifetime risk of stroke has increased by 50% over the last 17 years [3]. In Indonesia, prevalence rose 56% between 2013 and 2018, increasing from 7 to 10.9 per 1,000 individuals [7]. This surge imposes a significant economic burden; national health insurance (BPJS Health) data showed stroke-related costs escalated from IDR 2.19 trillion in 2016 to IDR 2.57 trillion in 2018 [12].

Ischemic stroke accounts for 62% of all cases [3], primarily driven by large artery atherosclerosis (59.6%) and small vessel disease (26.7%) [6]. While mechanical thrombectomy (MT) is highly effective for large vessel occlusions, approximately one-third of patients remain functionally dependent despite successful recanalization [4]. This discrepancy is often attributed to impaired microvascular reperfusion (IMR) caused by polymorphonuclear (PMN) leukocyte adhesion and platelet-fibrin blockage [2,10,11].

Experimental studies suggest that antithrombotic agents may mitigate this by preventing microvascular occlusion [1,2]. For instance, heparin may limit microthrombus development and restore perfusion during MT. However, these agents also increase the risk of symptomatic intracranial hemorrhage, which often leads to permanent disability or death [5]. Currently, the precise balance between the benefits and risks of antithrombotic use during MT remains poorly defined. This study aims to compare the clinical outcomes of antithrombotic administration in acute ischemic stroke patients undergoing mechanical thrombectomy.

METHODS

We searched PubMed, ScienceDirect, and Google Scholar for studies on acute ischemic stroke patients, antithrombotic agents, and mechanical thrombectomy. The keywords used were ((antithrombotic) OR (antiplatelet) OR (anticoagulant)) AND ((mechanical thrombectomy) OR (thrombectomy)) AND ((acute ischemic stroke) OR (non-hemorrhagic stroke) OR (ischemic stroke)). Only studies published between 2019 and 2024 and available in English were further analyzed.

This research included acute ischemic stroke patients who received antithrombotic drugs and mechanical thrombectomy for recanalization. The unexposed group undergoes mechanical thrombectomy without antithrombotics. The study shows safety and efficacy. Safety endpoints consisted of symptomatic intracranial hemorrhage (sICH) and death at 3-6 months, while effectiveness outcomes comprised successful recanalization (TICI/eTICI/mTICI >2b).

The impact of antithrombotic agents on sICH risk, mortality, recanalization success, and functional independence in acute ischemic stroke patients receiving MT was studied in observational studies (TICI/eTICI/mTICI ≥2b, mRS). 1) use of antithrombotic agents during mechanical thrombectomy procedure, 2) adult patients (≥18 years), 3) follow-up period of at least three months, 4) study publication in the range of 2019-2024, and 5) available in English. Meanwhile, studies were excluded from this study if, 1) the study was a case series or case report, editorial, commentary, review, or no data, 2) the study did not include any of the safety and efficacy outcomes that had been determined in the study, 3) or if antithrombotic agents were administered exclusively as chronic pre-stroke therapy or as post-procedural secondary prevention, without intra-procedural use during mechanical thrombectomy. This includes antithrombotic agents-administered only before MT as long-term, initiated >24 hours after MT solely for secondary stroke prevention, or used without clear a temporal relation to the MT procedure

Next, the authors independently assessed all included studies’ quality and bias using the observational research Newcastle-Ottawa Scale. Assessment findings were categorized as low (<5 points), medium (5-7 points), and high (>7 points). Data were pooled using the Mantel-Haenszel fixed-effects model with an odds ratio (OR) effect size and 95% CI. Higgins I² assessed group statistical heterogeneity. We defined substantial heterogeneity as I² >50% and no heterogeneity as I²=0. All analyses used Review Manager Web Version, defined as p-value <0.05, were filed with PROSPERO under registration number CRD42024522549 before the beginning of the search.

RESULTS

The initial search strategy yielded 7,339 studies. Then, after the overall study evaluation, out of 496 potentially eligible studies, the systematic review and meta-analysis comprised 13 papers (Fig. 1).

All studies had a retrospective or prospective observational study design. In safety outcomes, all studies included data on the incidence of sICH, while only 11 studies included mortality data within 3-6 months. Only 11 out of 13 studies in efficacy outcomes included data for each outcome parameter of successful recanalization and functional independence in 3-6 months.

The 13 investigations comprised Asian and European populations (Table 1). Of 4,923 patients studied, 1,713 were exposed, and 3,210 were unexposed. The ages were 62-75. No study had a high risk of bias on the NOS. All studies were intermediate quality. According to the research, antithrombotic medications during MT did not significantly reduce sICH risk. SICH outcomes showed OR 0.83 (95% CI 0.63-1.1); p=0.19; I²=25% (Fig. 2). For the 3-to 6-month mortality outcome, antithrombotic agents during MT operation substantially reduced risk with a tight CI, despite considerable heterogeneity (OR 0.57 (95% CI 0.33-0.99); p=0.05; I²= 86%). This is shown by the consistency of results in most research, except Baik and Zhu (Fig. 3).

The use of antithrombotic agents during MT increased the risk of successful recanalization (TICI/eTICI/mTICI ≥2b), but was not statistically significant due to inconsistency across studies (OR 1.22 (95% CI 0.81-1.83); p=0.63; I²=74%) (Fig. 4). The similar result was seen for functional independence (mRS 0-2): OR 1.07 (95% CI (0.81-1.41); p=0.31; I²=73%] (Fig. 5).

DISCUSSION

This meta-analysis comprehensively examined the impact of intra-procedural antithrombotic agents during MT for acute ischemic stroke. Our pooled findings indicate that while these agents do not significantly influence the likelihood of successful recanalization or functional independence, they also do not increase the risk of symptomatic intracranial hemorrhage (sICH). Notably, their use was associated with a significant reduction in mortality at 3-6 months. These results suggest that while antithrombotic therapy may not directly enhance immediate reperfusion or functional recovery, it may improve survival through systemic mechanisms or the prevention of recurrent thromboembolic events.

Safety outcomes

The lack of association between intra-procedural antithrombotic use and sICH risk reinforces the procedural safety of these agents. Our findings align with Van de Graaf et al. (2018), who reported that intraprocedural administration did not elevate bleeding risks or worsen neurological outcomes [8,13]. Similarly, Yang et al. (2019) observed that heparinization during MT did not increase hemorrhagic complications in the ANGEL registry [15]. Collectively, these data suggest that when appropriately dosed, intra-procedural anticoagulation is safe, even within the high-risk environment of reperfusion therapy.

Efficacy outcomes

Regarding efficacy, our analysis revealed no significant differences in successful recanalization or functional independence. This supports previous evidence suggesting that mechanical factors, clot composition, device performance, and collateral flow are the primary determinants of recanalization success, rather than pharmacological adjuncts [14]. Consequently, MT outcomes appear largely dependent on endovascular technique, with antithrombotic agents playing a secondary or supportive role.

Mortality and potential mechanisms

The most clinically significant finding is the association between intra-procedural antithrombotic use and reduced 3-6-month mortality. Several hypotheses may explain this protective effect. Antithrombotic agents may prevent early re-occlusion or distal embolization following clot retrieval, sustaining microvascular perfusion and mitigating reperfusion injury [15]. Furthermore, improved systemic hemodynamics and decreased recurrent embolic risk could contribute to a survival benefit, even if functional scores remain unchanged.

Clinical implications

These findings suggest that the judicious use of antithrombotics may be beneficial, particularly in patients with large clot burdens, tandem lesions, or underlying atherosclerotic disease where stabilizing microcirculation is critical. Ma et al. (2021) demonstrated that low-dose heparin or tirofiban can be safely administered when guided by strict intra-procedural monitoring [9].

Limitations and future perspectives

Despite these promising insights, several limitations exist. High study heterogeneity regarding drug type, dosage, and timing may affect the pooled estimates. Furthermore, most included data are retrospective, carrying risks of selection bias and confounding by indication. Long-term outcomes beyond six months also remain understudied. Future randomized controlled trials (RCTs) are necessary to determine optimal dosing and identify specific patient cohorts most likely to benefit. Integrating advanced imaging biomarkers, such as microvascular patency, could provide deeper mechanistic insights into the link between pharmacologic intervention and reduced mortality.

CONCLUSIONS

Antithrombotic drugs during MT operations did not increase the incidence of sICH but did lower death in 3-6 months. Regarding efficacy outcomes, its use also did not cause differences in successful recanalization and functional independence outcomes between groups that did not receive antithrombotic agents during MT procedures.

NOTES

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Fig. 1.

Flowchart of the systematic search process according to PRISMA

Fig. 2.

Forest plot of sICH events

Fig. 3.

Forest plot of mortality at 3-6 months

Fig. 4.

Forest plot of successful recanalization

Fig. 5.

Forest plot of functional independence (mRS 0-2)

Table 1.

Baseline characteristics of all studies

No	Author, Year	Country	Study design	Study center	Total population (n)	Population MT + Antithrombotic (n)	Population MT alone (n)	Age		Antithrombotic agents	Antithrombotic agents administration protocol	Therapeutic strategies	Baseline NIHSS		Therapeutic strategies
No	Author, Year	Country	Study design	Study center	Total population (n)	Population MT + Antithrombotic (n)	Population MT alone (n)	MT + Antithrombotic	MT alone	Antithrombotic agents	Antithrombotic agents administration protocol	Therapeutic strategies	MT + Antithrombotic	MT alone	Therapeutic strategies
1	Baik et al., 2021	Korea	Retrospective observational study	Single-center	114	45	69	74 (4)	75 (4.25)	Urokinase	Microcatheter (0.021 or 0.027 inch) local intra-arterial urokinase was done. The microcatheter was first passed over the thrombus and put distal. UK injection began after antegrade contrast opacification beyond the occlusion site.	MT with stent retriever or contact aspiration	15 (2)	15 (1.75)	3 months
2	Cai et al., 2022	China	Retrospective observational study	Single-center	285	48	237	69 (4.5)	71.25 (4.3)	Tirofiban (antiplatelet)	Tirofiban was administered at 8 μg/kg/hour following a 10 μg/kg intravenous bolus if no ICH was seen on head CT after MT.	MT with stent retriever	14 (1.75)	14 (1.17)	90 days
3	Chen et al., 2022	China	Retrospective observational study	Multi-center	645	363	282	63 (2.5)	65 (2.67)	Tirofiban (antiplatelet)	Starting at 0.4 for 30 min, progress to 0.1 μg/kg/min for up to 24 hours	MT with stent-retriever and/or local aspiration devices	27 (2.67)	27 (5.19)	1 year
4	Cho et al., 2023	Korea	Retrospective observational study	Single-center	87	16	71	63.12 (4.4)	74 (3.33)	Tirofiban (antiplatelet)	0.5 mg (2 mL) tirofiban in 8 mL normal 1 mL/min. For tirofiban addition, the same approach was utilized on follow-up angiography immediately and 10 min after IA infusion. The total IA tirofiban infusion was 0.5-2.0 mg.	MT with stent retriever or contact aspiration	45.75 (1.71)	19.25 (1.46)	90 days
5	Guan et al., 2023	China	Retrospective observational study	Multi-center	204	102	102	68 (5.46)	72.7 (4.10)	Tirofiban (antiplatelet)	Tirofiban is infused intravenously at 0.1 μg/kg/min for 12-24 hours after a low-dose intra-arterial bolus injection.	MT with stent retriever, aspiration and/or balloon angioplasty	13.25 (2.04)	15.1 (3.62)	90 days
6	Huo et al., 2020	China	Retrospective observational study	Single-center	207	55	152	62.5 (13.8)	64.4 (12.5)	Tirofiban (antiplatelet)	Low-dose intra-arterial bolus and continuous IV infusion were given for 12-24 hours.	MT with stent retriever or aspiration and preceding intravenous thrombolysis	18 (2.25)	15 (1.33)	3 months
7	Huo et al., 2021	China	Retrospective observational study	Multi-center	649	244	405	64 (55-70.5)	63 (54-71)	Tirofiban (antiplatelet)	Low dose intra-arterial bolus (0.25-1 mg) of tirofiban	MT with stent retriever or aspiration	14 (1.79)	13 (1.75)	90 days
8	Ma et al., 2021	China	Prospective observational study	Multi-center	201	81	120	62 (2.67)	65 (2.17)	Tirofiban (antiplatelet)	Low dose intra-arterial bolus (0.25-1.00 mg) tirofiban followed by a continuous intravenous tirofiban infusion (0.1 μg/kg/min) was administrated for 24 hours.	MT with stent retriever or aspiration device	15 (1)	14 (1.17)	3 months
9	Ma et al., 2022	China	Matched control analysis	Multi-center	928	102	826	63 (2)	67 (3)	Eptifibatide (antiplatelet)	A single intravenous or intra-arterial bolus of 135-180 μg/kg over <5 minutes a continuous infusion of 0.75-2.0 μg/kg/min for 24 hours.	MT	17 (1.67)	15 (1.67)	3 months
10	Yang et al., 2023	China	Retrospective observational study	Multi-center	619	269	350	63.6 (14.7)	64.1 (12.9)	Heparin (antikoagulan)	Unfractionated heparin was first administered at 50-100 IU/Kg and thereafter 1,000 IU per hour throughout surgery.	MT with stent retriever or aspiration device	17 (1.33)	16 (1.83)	3 months
11	Yi et al., 2019	Korea	Retrospective observational study	Multi-center	327	47	280	73.4 (15.6)	69.1 (16.1)	Tirofiban (antiplatelet)	A 0.25 mg tirofiban bolus in 20 mL of normal saline was administered over 5 min (0.05 mg/min). An angiography was then done via guiding. Additional stent retriever or IA tirofiban infusions (maximum dosage of 1.0 mg) were undertaken if there were still occlusions.	MT with stent retriever	10.5 (4.25)	9.6 (2.83)	3 months
12	Zhao et al., 2021	China	Retrospective observational study	Single-center	288	117	171	70.1 (11.0)	69.6 (11.0)	Tirofiban (antiplatelet)	Low-dose tirofiban hydrochloride and sodium chloride injections were given intra-arterially at 1 mL/min (0.25 mg to 0.5 mg), then intravenously at 4 to 8 mL/h (0.2 to 0.4 mg/h) for 12 to 24 hours.	MT with stent retriever	16.5 (1)	16 (1.08)	3 months
13	Zhu et al., 2019	France	Retrospective observational study	Multi-center	369	224	145	64 (12.6)	62.8 (12.1)	Aspirin, clopidogrel, or glycoprotein 2b/3a receptor antagonist (anti-Gp2b/3a)	Antiplatelet therapy was administered during the EVT at operator discretion	MT with stent retriever or a direct aspiration, first pass technique (ADAPT)	15.3 (6.3)	16.3 (5.2)	90 days

n, number; MT, mechanical thrombectomy; SD, standard deviation; NIHSS, National Institutes of Health Stroke Scale; UK, urokinase; ICH, intracerebral haemorrhage; IA, intra-arterial; IV, intravenous; EVT, endovascular therapy; CT, computed tomography

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