Perioperative Antiplatelet Therapy in the New Flow Diversion Era

Abstract

Flow diverter (FD) technology has provided a new concept for the treatment of intracranial aneurysms: reconstruction of the parent artery by covering the neck with a braided mesh stent. It has enabled us to treat not only saccular aneurysms but also complex aneurysms that were previously considered difficult or impossible to treat. Despite its clinical impact, FD remains associated with thromboembolic and hemorrhagic complications, both of which are closely related to perioperative antiplatelet therapy. Dual antiplatelet therapy (DAPT), consisting of aspirin combined with a P2Y12 inhibitor, has traditionally been adopted as the standard strategy to reduce thromboembolic risk. However, the optimal regimen remains poorly defined, and substantial variability exists in clinical practice. Recent evidence suggests that the risk of thromboembolism is highest in the early perioperative period, while prolonged antiplatelet therapy may expose patients to unnecessary bleeding risks without clear additional benefits. In parallel, advances in platelet function testing, the availability of potent P2Y12 inhibitors, and the development of surface-modified FD devices are prompting reconsideration of the conventional paradigm of prolonged DAPT. This review provides a comprehensive synthesis of current evidence on perioperative antiplatelet therapy in the context of flow diversion and proposes a contemporary framework that emphasizes temporal risk stratification and individualized treatment strategies.

Introduction

The introduction of flow diversion has fundamentally altered the therapeutic landscape for intracranial aneurysms. Traditional endovascular treatments, such as coil embolization with or without stent-assisted techniques, aim to occlude the aneurysm sac itself with as many coils as possible; however, their application to aneurysms with unfavorable morphologies, which are prone to incomplete occlusion even with adjunctive techniques, remains limited. In contrast, flow diverters (FDs) promote aneurysm healing by covering the neck with a braided mesh stent, redirecting blood flow away from the aneurysm, and promoting gradual thrombosis within the sac.^1–3) This paradigm shift has expanded the range of treatable aneurysms, particularly those that are large/giant, complex with incorporated branches, wide-necked, or fusiform in morphology.^4–7)

However, this advance is accompanied by a higher complication rate than that of conventional techniques.^8–11) High metal coverage of FD devices can cause platelet aggregation and thrombus formation within the aneurysm sac and the implanted stent, resulting in a serious thromboembolic complication such as in-stent occlusion. This risk persists until complete endothelialization of the FDs, which may take several months in animal models.¹²⁾

To reduce thromboembolic complications, perioperative antiplatelet therapy has become an essential element of FD treatment.¹³⁾ Dual antiplatelet therapy (DAPT), typically combining aspirin and clopidogrel, has been widely adopted based on early clinical trials and experience.^4,5,14–16) While DAPT effectively reduces thromboembolic complications, it simultaneously increases the risk of hemorrhagic events, including intracranial hemorrhage, gastrointestinal bleeding, and complications related to additional surgical procedures, such as ventricular drainage.¹⁷⁾

Balancing thrombosis prevention and bleeding risk is a central challenge in the perioperative management of FD patients. Recent accumulated evidence suggests that the risk of thromboembolism is not persistent indefinitely but rather tends to occur frequently in the early postoperative period and then decrease thereafter.¹⁵⁾ Conversely, the bleeding risk associated with antiplatelet therapy may continue and accumulate over time. Based on ethnic characteristics, East Asians have a higher risk of intracranial hemorrhage compared to other races,¹⁸⁾ and long-term DAPT is ineffective in reducing ischemic risk and may even significantly increase bleeding risk.¹⁹⁾

These observations have led to increasing recognition that a classic, prolonged DAPT strategy may not be optimal for all patients, especially East Asians who are at high risk of intracranial hemorrhage. Rather, there is a growing need to tailor antiplatelet therapy according to individual risk profiles, procedural characteristics, and evolving device technologies such as surface modification.

In this review, we examine the mechanism of thrombogenicity in FD, the role of antiplatelet therapy and the variability of its pharmacologic reactivity, and the evolving evidence regarding a “sweet-spot regimen” balanced between thrombogenicity and hemorrhage. Ultimately, we propose a contemporary framework that transitions from prolonged empiric therapy toward dynamic and individualized management.

Mechanisms of Thrombosis in Flow Diversion

The thrombogenicity associated with FDs is multifactorial and arises from the interplay between device characteristics, arterial wall injury, and local hemodynamic conditions. Unlike conventional intracranial stents, FDs are designed with high metal surface coverage, often exceeding 30%–35%, and consist of densely braided wires made of cobalt–chromium, platinum–tungsten, tantalum, and nitinol.²⁰⁾ This high-density mesh significantly alters blood flow patterns from the aneurysm sac to the parent artery, leading to thrombosis within the aneurysm dome and endothelialization of the aneurysm orifice.^13,21,22)

Platelet activation mediated by implanted FD

Immediately following implantation, the metallic surface of the device is exposed to circulating platelets and coagulation factors. Platelet adhesion and activation occur rapidly, mediated by interactions between platelet receptors and the surface of the implanted FD. Activated platelets release prothrombotic mediators, further amplifying the aggregation cascade and promoting thrombus formation.

Endothelial injury during FD procedure

In addition to device-related factors, endothelial injury during device deployment also contributes to thrombus formation. Mechanical manipulation of the guiding/intermediate catheter, microcatheter, or wire results in localized endothelial injury, exposing subendothelial matrix, including collagen, which further stimulates platelet activation.

Hemodynamic change after FD implantation

Hemodynamic changes induced by FD implantation also play a critical role. FD reduces intra-aneurysmal velocity and promotes flow stasis within the aneurysm sac, a step that is essential for thrombosis followed by aneurysm healing. However, when thrombosis within the aneurysm sac progresses rapidly, there is a risk that thrombosis will extend into the stent. At the level of the incorporated branches, disturbed flow patterns can facilitate platelet aggregation and thrombus formation, potentially leading to unintended occlusion of incorporated branches.

Endothelialization and thrombosis

The initial concept of FDs was that intra-aneurysmal thrombosis by flow reduction led to aneurysm occlusion. However, Ravindran et al. have stated that the healing mechanism of FDs cannot be explained by thrombosis alone, but that arterial remodeling is achieved through a sequential process involving hemodynamic change, thrombosis, neointimal formation, and endothelialization.^21,22)

Endothelial cells gradually cover over the device struts, forming a neointimal layer that effectively isolates the aneurysm from circulating blood. Systematic experimental and clinical studies have proposed that endothelialization occurs in 2 phases: rapid coverage of the device within the parent artery and slower endothelial bridge formation across the aneurysm neck. Experimental studies have further demonstrated that platelet adhesion to exposed device struts, endothelial injury during device deployment, and local flow alterations collectively initiate thrombus formation. Subsequently, endothelial cell migration and neointimal formation gradually reduce device thrombogenicity.²¹⁾

This process is essential for long-term aneurysm occlusion. It is not immediately completed and can vary depending on the implanted device, vessel morphology, and patient-specific factors. In some cases, this process can lead to delayed in-stent stenosis by intimal hyperplasia or occlusion of jailed branches, but 86.8%, 93.4%, and 95.2% of patients can achieve aneurysm occlusion at 1, 3, and 5 years, respectively.⁶⁾ As endothelialization progresses, the thrombogenicity of the device itself decreases. The problem is that it is not possible to visually assess the progress of endothelialization. If this were possible, it might be possible to more appropriately determine when to de-escalate or discontinue antiplatelets. Animal studies using high-resolution imaging techniques such as optical coherence tomography (OCT) have provided important insights into the dynamics of endothelialization. These studies have shown that endothelial coverage of the implanted FD begins soon after implantation, increases over time, and is completely covered by day 21.^23,24) Taken together, these findings underscore that the risk of thrombosis is highest during the early post-implantation phase, when the device surface remains exposed because of incomplete endothelialization. However, as endothelialization progresses, the risk of thrombosis decreases and eventually almost disappears. This has significant implications in designing antiplatelet therapy strategies.

Conventional Antiplatelet Strategies (Current Practice)

Establishment of DAPT as standard of care

DAPT has become the standard perioperative regimen in FD treatment, largely based on early clinical trials and subsequent observational studies. In these pivotal studies, including the PUFS trial and the initial Pipeline Embolization Device (Medtronic, Irvine, CA, USA) experience, patients were pretreated with aspirin and clopidogrel, typically initiated several days before the procedure, and continued clopidogrel therapy for a minimum of 30 days and aspirin therapy for a minimum of 180 days after implantation.^4,5) These treatments, despite being established without scientific evidence and based solely on antiplatelet therapy in coronary intervention and empirical evidence, have been widely accepted worldwide and incorporated into routine clinical practice.

As this treatment method became more widespread, reports of delayed, severe thromboembolic complications occurring when the medication was reduced or discontinued began to appear.²⁵⁾ Despite the lack of clear evidence that the de-escalation or discontinuation of the antiplatelets was the cause, concerns about this led to a gradual extension of the administration period.

Subsequent early clinical trials showed a trend toward DAPT extension therapy, which involved continuing clopidogrel therapy for at least 3 months and aspirin for 6 months or more, and in some cases for life.^10,26,27) Currently, the most frequently used antiplatelet therapy consists of 6 months of DAPT therapy followed by 6 months of monotherapy, for a total treatment period of 12 months.^14,28)

Emergence of potent P2Y12 inhibitors

In response to the limitations of clopidogrel, newer-generation P2Y12 inhibitors such as prasugrel and ticagrelor have gained increasing attention in neuroendovascular practice. These agents offer more predictable pharmacokinetics and pharmacodynamics, with rapid onset of action and reduced variability in platelet inhibition.¹³⁾

Ticagrelor, in particular, has been extensively studied in this context. Unlike clopidogrel, ticagrelor is a direct and reversible P2Y12 inhibitor that does not require metabolic activation. Consequently, it is less affected by genetic polymorphisms and provides more consistent platelet inhibition.

Comparative studies evaluating ticagrelor versus clopidogrel in FD procedures have demonstrated similar rates of thromboembolic and hemorrhagic complications.^29–31) Importantly, studies have also shown that switching clopidogrel hypo-responders to ticagrelor significantly reduces the incidence of thromboembolic events.³²⁾

Prasugrel, another potent P2Y12 inhibitor, has also been used in selected patients, particularly in those with clopidogrel resistance. In the ACUTE-PRAS study, prasugrel resulted in stable inhibition of platelet aggregation compared with clopidogrel, regardless of CYP2C19 polymorphisms.³³⁾ However, concerns regarding bleeding risk, especially in certain populations, have limited its widespread use.

Overall, these newer agents represent an important step toward more reliable and individualized antiplatelet therapy.

Limitations of Current Strategies

Variability in response to antiplatelet therapy

A major challenge in the optimization of antiplatelet therapy is the substantial interindividual variability in drug response. The response to each antiplatelet varies from patient to patient; however, clopidogrel, the most widely used P2Y12 inhibitor in neuroendovascular treatment, exhibits particularly high variability due to its pharmacokinetic and pharmacogenetic characteristics.

P2Y12 receptor antagonists, such as clopidogrel, prasugrel, or ticagrelor, exert an antiplatelet action by inhibiting the adenosine diphosphate P2Y12 receptor. Among them, thienopyridines are prodrugs that need to be metabolized and converted into active metabolites in the liver by the cytochromes and irreversibly inhibit the P2Y12 receptor. Clopidogrel metabolism predominantly depends on CYP2C19, which has many genetic variants that influence metabolism speed, affecting the antiplatelet effect.^34,35) Patients with the CYP2C19-poor metabolism variant related to impaired function have reduced platelet inhibition and are classified as “hypo-responders.” The CYP2C19 genotype is the most common factor for clopidogrel hypo-responsiveness.

Clinical studies have consistently demonstrated that clopidogrel hypo-responsiveness is associated with increased thromboembolic complications following FD^32,36,37) and stent-assisted coiling.^38,39) Conversely, excessive platelet inhibition, particularly in hyper-responders, is associated with increased risk of hemorrhagic complications.^36–39) This bidirectional risk highlights the importance of achieving an optimal level of platelet inhibition; therefore, platelet function tests are used to evaluate antiplatelet effects and provide a chance to switch or change doses of antiplatelet agents before neuroendovascular treatment.

Limitations of conventional DAPT: Delayed thrombotic events

Although early thromboembolic complications account for most adverse events, delayed thrombosis remains an important concern. Clinically, delayed thrombosis may manifest as transient ischemic attack, ischemic stroke, or in-stent thrombosis.^25,40) Although infrequent, these events can have severe consequences. These events can occur weeks to months after the procedure and are sometimes associated with cessation or interruption of antiplatelet therapy.

Several risk factors for delayed thrombosis have been identified. Aneurysm characteristics play a significant role, with large, giant, and fusiform aneurysms associated with increased risk.⁴¹⁾ These lesions often require multiple overlapping devices, which further increase metal coverage and thrombogenic potential. In addition, coverage of side branches or perforating arteries may contribute to delayed complications. The presence of multiple devices and incomplete endothelialization may prolong the thrombogenic period.

Experimental studies provide important insights into the mechanisms underlying delayed thrombosis. As demonstrated in OCT-based models, insufficient antiplatelet therapy can lead to accelerated neointimal proliferation, particularly at branch ostia.¹²⁾ This process may result in progressive narrowing and eventual occlusion of covered branches and influence clinical outcomes and the optimal duration of antiplatelet therapy.

Consequently, the duration of DAPT tends to be extended, particularly in patients at high risk of delayed thrombosis, necessitating careful determination of the optimal timing for transition to single antiplatelet therapy (SAPT) or discontinuation of antiplatelet therapy.

Limitations of conventional DAPT: Hemorrhagic risk

Among the limitations of conventional DAPT, hemorrhagic complications associated with prolonged antiplatelet therapy represent a particular concern.^42,43) This issue is especially relevant in East Asian patients.^18,19)

Patients may require bleeding control due to access-site hematoma, intracranial hemorrhage, gastrointestinal bleeding, or trauma. Unfortunately, both aspirin and clopidogrel are irreversible antiplatelet drugs, and there are no antagonists, so the antiplatelet effect will persist for several days. Therefore, patients may experience more serious conditions.

In addition, prolonged DAPT poses challenges in the management of patients who require subsequent surgical interventions, including craniotomy, cerebrospinal fluid drainage, or ventriculoperitoneal shunt placement. In such cases, interruption of antiplatelet therapy may increase thrombotic risk, whereas continuation increases bleeding risk, creating a difficult clinical dilemma.¹³⁾

These limitations highlight the need for more flexible approaches to antiplatelet management.

Platelet Function Testing and Individualized (Tailored) Antiplatelet Therapy

Platelet function tests

To address variability in antiplatelet response, platelet function tests have been increasingly adopted in clinical practice. Among the available assays, the VerifyNow P2Y12 assay (Werfen, Bedford, MA, USA) is the most widely used due to its rapid turnaround time and ease of use.²⁸⁾ The test provides a quantitative measure of platelet reactivity expressed as P2Y12 reaction units (PRU).

Multiple observational studies and meta-analyses have examined the relationship between PRU values and clinical outcomes in patients undergoing FD.^32,36,37) These studies have identified a therapeutic window of platelet inhibition within which the risk of both thromboembolic and hemorrhagic complications is minimized. Specifically, higher PRU values, typically above approximately 240, are associated with insufficient platelet inhibition and increased risk of thromboembolism. In contrast, lower PRU values, generally below approximately 60, are associated with excessive platelet inhibition and increased risk of bleeding complications.³⁷⁾

Tailored antiplatelet therapy

These findings provide a mechanistic rationale for individualized antiplatelet therapy based on platelet reactivity. In practice, many centers adjust antiplatelet regimens according to PRU values, switching from clopidogrel to more potent agents such as ticagrelor or prasugrel in patients with inadequate response. Guided, tailored antiplatelet therapy has shown some efficacy in neuroendovascular treatment⁴⁴⁾ or percutaneous coronary interventions.^45,46)

However, despite the logical appeal of this approach, the routine use of platelet function testing remains controversial. Randomized controlled trials demonstrating improved clinical outcomes with guided therapy are lacking, and some studies have shown acceptable outcomes without routine testing.⁴⁾ Nevertheless, in the context of flow diversion, where the consequences of thrombotic and hemorrhagic complications can be severe, platelet function testing continues to play an important role in many patients.

Recent Trends in Antiplatelet Management

Wide variability in clinical practice

One of the most striking features of antiplatelet management in FD is the substantial variability in DAPT duration across institutions. Survey-based studies, including large national and international analyses, have revealed that most centers administer DAPT for 3 to 6 months following FD implantation, although shorter and longer regimens are also reported.^14,28) This heterogeneity reflects the lack of high-quality evidence defining optimal duration. In the absence of randomized controlled trials, clinicians have relied on institutional experience, device characteristics, and perceived patient risk.

Thromboembolic events after FD: When do they occur?

A key insight that has emerged from recent observational studies is that thromboembolic events are not uniformly distributed over time. It has been shown that most ischemic complications occur within the first 30 days after the procedure, with a steep decline in incidence thereafter.¹⁵⁾ This pattern is consistent with the biological process of endothelialization. During the early post-implantation phase, the device surface remains exposed and thrombogenic, necessitating robust platelet inhibition. As endothelial coverage progresses, the thrombogenic potential diminishes, reducing the need for intensive therapy.

Importantly, late thromboembolic events, although possible, are relatively uncommon and were observed mainly in fusiform aneurysms where normal intimal coverage is unlikely.²⁵⁾ This observation raises a critical question: if the period of highest risk is confined to the early phase, is prolonged DAPT beyond this period truly necessary?

Short-duration versus long-duration DAPT

Several studies have sought to address this question by comparing outcomes between shorter and longer durations of DAPT. Although randomized data are limited in stent-assisted coiling,⁴⁷⁾ observational studies and registry analyses provide valuable insights.^15,16) In a Japanese multicenter cohort study on FD and stent-assisted coiling, no difference was observed in the incidence of ischemic events after switching to monotherapy between the long-term DAPT (3 months or more) group and the short-term DAPT (less than 3 months) group.¹⁵⁾ In a South Korean cohort study, the 3 months of DAPT was associated with a decreased risk of the composite of ischemic and hemorrhagic complications compared with the extended DAPT group.¹⁶⁾

These data are from East Asian populations, where both clopidogrel metabolism and higher bleeding risk profiles suggest that shorter DAPT regimens may be both safe and advantageous. Taken together, these findings challenge the traditional paradigm of prolonged DAPT and suggest that shorter regimens may be sufficient for many patients.

Ongoing clinical trials and future directions

Recognizing the limitations of existing evidence, several ongoing randomized trials aim to directly compare short-duration versus long-duration DAPT in the field of coronary intervention.^48–52) There is already momentum for ultra-short-term DAPT, such as an “aspirin-free” strategy, in coronary intervention.^49,50,52)

While there are no results from randomized controlled trials regarding the optimal duration of drug administration for FD, these studies are expected to provide more definitive guidance regarding optimal therapy duration.

Rationale for SAPT for FD

Given the limitations of prolonged DAPT, there has been increasing interest in the use of single antiplatelet therapy, particularly in selected patient populations. The rationale for SAPT is based on the observation that the highest thrombotic risk is confined to the early phase and that modern devices may be less thrombogenic than earlier generations.

In addition, the availability of more potent and consistent P2Y12 inhibitors raises the possibility that monotherapy with these agents may provide sufficient platelet inhibition.

A multicenter study evaluating ticagrelor monotherapy reported favorable outcomes, with no significant increase in thromboembolic complications during both early and late follow-up periods.⁵³⁾ Similarly, some cohort studies for FD using surface-modified devices suggest that SAPT may be as effective as DAPT.^54–56) Despite these promising findings, SAPT cannot yet be considered standard of care. The available data are limited and often derived from small, non-randomized studies.

SAPT may be appropriate in patients with low-risk aneurysm morphology (avoided for fusiform aneurysms), single-device implantation, and the use of surface-modified devices.⁵⁷⁾ Conversely, patients with complex aneurysms or high thrombotic risk likely still require DAPT.

Surface Modification

Recent years have seen significant advances in FD design, particularly with the introduction of surface-modified devices aimed at reducing thrombogenicity. These innovations include the application of biocompatible coatings such as phosphorylcholine or hydrophilic polymers to the device surface.

These coatings are designed to mimic the antithrombotic properties of the native endothelium and reduce platelet adhesion.

Preclinical studies have demonstrated that surface modification reduces platelet activation and thrombus formation.^22,58) In animal models, coated devices show reduced thrombogenicity compared with bare-metal devices.

Clinical studies have begun to confirm these findings. Early data suggest that surface-modified devices are associated with low rates of thromboembolic complications and may allow for reduced antiplatelet intensity.

The development of surface-modified devices has important implications for antiplatelet therapy. By reducing the intrinsic thrombogenicity of the device, these technologies may allow:

• shorter duration of DAPT

• earlier de-escalation to SAPT

• potential SAPT-only strategies for low-risk patients

This represents a major step toward the goal of individualized and simplified antiplatelet therapy.

Future Directions in Antiplatelet Therapy for Flow Diversion

A practical clinical framework for antiplatelet management

Although definitive guidelines remain lacking, available evidence allows for the construction of a pragmatic clinical framework that reflects current best practices and evolving concepts.

In the preprocedural phase, patients are typically initiated on DAPT several days prior to FD implantation. This approach allows sufficient time to achieve steady-state platelet inhibition, particularly when using clopidogrel.¹³⁾ Platelet function testing, when available, can be used to identify hypo-responders and guide adjustment of therapy, including switching to more potent P2Y12 inhibitors such as ticagrelor or prasugrel.^32,36)

During the procedural phase, systemic anticoagulation with heparin is routinely administered to prevent acute thrombus formation.^14,59) In cases of intraoperative thrombosis, rescue therapies such as glycoprotein IIb/IIIa inhibitors may be employed in other countries,^60–63) but it is important to note that they are not available in Japan. Therefore, it is necessary to ensure that a sufficient antiplatelet effect is achieved before the procedure, and for patients at high thrombotic risk, the addition of concomitant anticoagulant therapy may be required despite its limited use in other countries.^14,59,63)

In Japan, the use of antiplatelet agents for this specific indication is not formally approved as an independent reimbursement item under the national health insurance system. These regulatory and reimbursement circumstances should be considered when interpreting international data and applying them to Japanese clinical practice.

In the early post-procedural phase, typically defined as the first 30 days after implantation, strict DAPT remains essential. This period corresponds to the highest risk of thromboembolic events, which may be due to incomplete endothelialization and high device thrombogenicity. Discontinuation or inadequate antiplatelet therapy during this phase is associated with a marked increase in complications.

Beyond the 1st month, the risk of thrombosis decreases as endothelialization progresses. In current clinical practice, approximately 3 months of DAPT remains the most commonly adopted minimum duration. De-escalation may be considered after 1 month in selected low-risk patients, whereas continuation of DAPT for at least 3 months remains appropriate for most patients. In many patients, either aspirin or a P2Y12 inhibitor is used as single antiplatelet therapy following DAPT^14,28); however, there is currently no clear consensus regarding the optimal agent.

In the late phase, beyond 6 months, thrombotic risk is generally low in patients with complete endothelialization and stable device integration. In selected low-risk patients, further simplification of therapy, including discontinuation of antiplatelet agents, may be considered, although robust evidence remains limited.

This phase-based framework aligns closely with the biological processes underlying thrombosis and healing after FD implantation (Fig. 1).

Fig. 1. Phase-based framework for antiplatelet management after FD placement. In the early phase, high thrombogenicity due to device exposure necessitates strict DAPT. As endothelialization progresses, thrombosis risk decreases, allowing de-escalation to SAPT in the intermediate phase. In the late phase, when endothelialization is complete, further simplification or discontinuation of antiplatelet therapy may be considered.

DAPT, dual antiplatelet therapy; FD, flow diverter; mo, month; SAPT, single antiplatelet therapy

Toward individualized antiplatelet therapy: Integrating patient, device, and temporal factors

With the limitations of conventional DAPT and the accumulation of evidence supporting shorter-duration regimens, there is growing recognition of the importance of treatment regimens that consider the risks of both thromboembolic and hemorrhagic complications.

However, patients undergoing flow diversion represent a highly heterogeneous population, and variations in factors such as aneurysm morphology, anatomical location, device configuration, platelet reactivity, and patient-specific biological factors contribute to differences in risk profiles.

Taken together, these considerations support a multidimensional model of antiplatelet management that integrates patient-specific, aneurysm-specific, device-specific, and time-dependent factors.

Future aspects

The field of antiplatelet therapy in flow diversion is changing, driven by advances in both pharmacology and device technology.

More potent P2Y12 inhibitors have improved platelet inhibition, and future agents that allow rapid modulation of platelet activity in emergency situations may become available, further enhancing safety and flexibility.

At the same time, surface-modified FDs are reducing thrombogenicity and may enable minimized antiplatelet regimens.

Advances in imaging and computational modeling could support personalized treatment decisions, and ongoing randomized trials will help define optimal regimens and treatment durations. Until stronger evidence becomes available, management will remain guided by existing data, expert opinion, and individual patient risk factors.

Conclusion

Perioperative antiplatelet therapy remains a cornerstone of safe and effective FD treatment. However, the optimal strategy is evolving as new evidence and technologies emerge.

Advances in platelet function testing, pharmacologic agents, and device technology are enabling a transition toward shorter, individualized strategies. This paradigm shift reflects a broader movement toward precision medicine, in which therapy is tailored to the unique characteristics of each patient and clinical scenario.

Future research, particularly randomized controlled trials, will be essential to define optimal protocols and establish evidence-based guidelines. Until then, we must continue to balance competing risks and apply a thoughtful, individualized approach to antiplatelet management in flow diversion.

Disclosure Statement

Yukiko Enomoto received a research grant from Medtronic and lecture fees from Terumo, Medtronic, and Dai-ichi Sankyo.