Dual Antiplatelet Therapy To Challenge Tirofiban For Safest Subarachnoid Hemorrhage Therapy
Overview
In the realm of treating aneurysmal subarachnoid hemorrhage patients with stent-assisted embolization, the management of perioperative complications, particularly thromboembolic events (TEs) and hemorrhagic events (HEs), is crucial, with antiplatelet protocols playing a pivotal role.
In this retrospective single-center analysis, a comparison was made between arteriovenous tirofiban administration and traditional oral dual antiplatelet therapy (DAPT). A cohort of 417 consecutive patients was examined, with a focus on their general clinical characteristics and the incidence of perioperative ischemic and hemorrhagic events, documented digitally. Logistic regression was employed to discern both risk and protective factors associated with these events.
Results unveiled that perioperative TEs were observed in 21 patients, reflecting an overall rate of approximately 5.04%. Notably, the tirofiban group exhibited a lower incidence of perioperative TEs compared to the DAPT group. Similarly, 66 patients experienced perioperative HEs, translating to an incidence of roughly 15.83%, with the tirofiban group demonstrating a lower occurrence of these events compared to the DAPT group. Interestingly, no significant disparities were noted between the two groups concerning the modified Rankin Scale (mRS) score at discharge.
In conclusion, the study suggests that the enhanced perioperative antiplatelet agent, tirofiban, serves as an independent protective factor against perioperative TEs in stent-assisted embolization of ruptured intracranial aneurysms. Importantly, this protective effect does not entail an increased risk of perioperative HEs and does not significantly influence the near-term prognosis of patients. These findings underscore the potential benefits of incorporating tirofiban into perioperative management strategies for improved outcomes in this patient population.
Introduction
Intracranial aneurysms, characterized by abnormal dilations in the walls of brain arteries, pose a significant health concern with a prevalence of about 3.2%. Ruptured intracranial aneurysms are a leading cause of subarachnoid hemorrhage, resulting in high mortality and disability rates, with approximately 30% of survivors experiencing moderate to severe disability. Surgical intervention is crucial for treating ruptured intracranial aneurysms, with two main approaches: microclamping and endovascular treatment.
The International Subarachnoid Hemorrhage Aneurysm Trial (ISAT) in 2002 established the safety and efficacy of endovascular embolization for intracranial aneurysms, making it the primary surgical option for many cases. Stent-assisted embolization therapy is a common approach, but it carries risks of perioperative thromboembolic events (TEs) and hemorrhagic events (HEs). Drug resistance to traditional antiplatelet drugs, particularly dual antiplatelet therapy (DAPT) with aspirin and clopidogrel, has been reported, potentially increasing the risk of ischemic events during endovascular therapy.
To address these challenges, platelet surface glycoprotein (GP) IIb/IIIa receptor antagonists like tirofiban have gained attention for their shorter half-life and faster recovery of platelet function. Combining tirofiban with arterial and venous routes has shown promise in preventing perioperative TEs without increasing the risk of HEs, compared to preoperative loading doses of dual antiplatelet drugs. Consequently, this study aims to identify high-risk factors for perioperative complications in stent-assisted embolization of ruptured intracranial aneurysms and assess the impact of modifying the antiplatelet protocol on coagulation and platelet counts during the immediate postoperative period.
Method
The retrospective study conducted at the Department of Neurosurgery of the First Affiliated Hospital of Army Medical University aimed to assess the impact of distinct perioperative antiplatelet protocols on patients undergoing treatment for subarachnoid hemorrhage (SAH). The research was conducted in adherence to the ethical standards outlined in the Declaration of Helsinki and was approved by the hospital’s Ethics Committee.
Patient data spanning from January 2010 to January 2023 were collected and divided into two groups based on the antiplatelet strategies employed: a group receiving loaded oral Dual Antiplatelet Therapy (DAPT) and another group receiving arteriovenous tirofiban administration. The sample consisted of 417 patients, with 63 in the loaded oral DAPT group and 354 in the arteriovenous tirofiban administration group.
Procedures involved comprehensive imaging techniques, including cerebral angiography under general anesthesia and 3D reconstruction to assess aneurysm size and morphology. Heparin was administered to maintain an appropriate activated clotting time during the procedure. Stent-assisted embolization was performed for ruptured aneurysms, with stents and coils selected randomly by one of three operators. Post-procedural evaluations included multi-angle angiography, 3D imaging, and Dyna CT to assess embolization grade and detect intraoperative bleeding.
Perioperative thromboembolic events (TEs) and hemorrhagic events (HEs) were meticulously defined, encompassing angiographic findings, ischemic symptoms, and imaging results. Patient data collected included demographic information, clinical history, laboratory parameters, and postoperative imaging findings. The modified Rankin Scale (mRS) score was employed to evaluate clinical outcomes at discharge.
The study’s comprehensive approach to data collection and analysis provides valuable insights into the outcomes associated with different perioperative antiplatelet protocols in SAH patients. The findings contribute to enhancing clinical management strategies and optimizing treatment approaches for this patient population.
Statistical Analysis
The statistical analysis of the study was conducted utilizing SPSS 26.0 software. Continuous variables, following a normal distribution, were presented as mean ± standard deviation, while qualitative and hierarchical variables were expressed as values and percentages. Categorical variables underwent analysis through the chi-square test, continuity correction, and Fisher’s precision test, whereas continuous variables were assessed using the t-test and the Wilcoxon rank-sum test.
Baseline characteristics such as age, sex, preoperative platelet count, aneurysm location and size, number of aneurysms in a single treatment, and previous medical history were compared between the two groups. Missing data accounted for less than 5% of all data, leading to the exclusion of variables with incomplete data from the analysis.
Both univariate and multivariate logistic regression analyses were employed to identify factors associated with perioperative thromboembolic events (TEs) and hemorrhagic events (HEs). Factors exhibiting a p-value of less than 0.1 in the univariate analysis were entered into the multivariate regression analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to determine the strength of associations.
Additionally, the study adhered to rigorous standards by registering in the Chinese Clinical Trial Registry under registration number ChiCTR2200067188, ensuring transparency and adherence to regulatory protocols. This meticulous approach to statistical analysis and registration underscores the study’s commitment to methodological rigor and scientific integrity.
Result
In this study encompassing 417 patients, including 124 males and 293 females, a total of 478 aneurysms were treated. The baseline characteristics of both patients and aneurysms displayed no significant differences between the groups. Notably, perioperative thromboembolic events (TEs) occurred in 21 patients, with a 5.04% incidence rate overall. Within the dual antiplatelet therapy (DAPT) group, 11.11% of patients experienced TEs, whereas in the tirofiban group, the incidence was 3.95%, representing a significant difference.
Furthermore, 37 patients experienced perioperative hemorrhagic events (HEs), with an overall incidence of 8.87%. In the DAPT group, 15.87% developed HEs, whereas in the tirofiban group, the incidence was 7.63%, again showing a significant difference. Postoperative coagulation profiles revealed significant differences in activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) between the two groups, with less coagulation observed in the tirofiban group.
In terms of patient outcomes, the modified Rankin Scale (mRS) scores at discharge did not significantly differ between patients experiencing perioperative complications in both groups. Case studies illustrated successful management of complications, including subarachnoid hemorrhage and acute thrombosis, with favorable outcomes upon discharge.
Logistic regression analysis identified perioperative antiplatelet therapy and dome-to-neck ratio < 2 as significantly associated with perioperative TEs, while aneurysm size was the sole factor independently associated with perioperative HEs. These findings underscore the importance of careful consideration of antiplatelet protocols and aneurysm characteristics in mitigating perioperative complications during stent-assisted embolization procedures.
In conclusion, the study provides valuable insights into the incidence and management of perioperative complications in patients undergoing stent-assisted embolization for aneurysms, emphasizing the significance of tailored antiplatelet strategies and thorough assessment of aneurysm characteristics to optimize patient outcomes.
Conclusion
This retrospective analysis aimed to investigate the impact of different antiplatelet protocols on the incidence of perioperative thromboembolic events (TEs) and hemorrhagic events (HEs) in patients undergoing stent-assisted embolization for ruptured intracranial aneurysms. The study found variations in the occurrence of perioperative TEs and HEs depending on the antiplatelet protocols used. Specifically, arteriovenous administration of tirofiban demonstrated effectiveness in preventing perioperative TEs without increasing the incidence of HEs. Logistic regression analysis supported these findings, revealing that a dome-to-neck ratio < 2 acted as a protective factor against perioperative TEs, while aneurysm size was associated with perioperative HEs.
The analysis involved 417 patients, with an overall perioperative TE rate of approximately 6.4%. The incidence of perioperative TEs was notably higher in the dual antiplatelet therapy (DAPT) group (12.3%) compared to the tirofiban group (5.3%), suggesting the efficacy of tirofiban in preventing thrombosis. Perioperative HEs occurred less frequently in the tirofiban group than in the DAPT group, although the choice of antiplatelet protocol was not a significant factor in multifactorial logistic regression.
Previous approaches often involved preoperative oral DAPT to prevent perioperative TEs in patients with unruptured intracranial aneurysms. However, the study supports the safety and efficacy of loading doses of DAPT in preventing perioperative thrombotic events during endovascular treatment of ruptured intracranial aneurysms with stent assistance. Tirofiban, initially used for acute ischemic stroke, has gained traction in endovascular therapy due to its promising prognosis. Current guidelines recommend its utilization for prophylaxis against perioperative ischemic events in ruptured aneurysms.
The study also investigated the dosing regimen of tirofiban, revealing that combined arteriovenous administration was effective in preventing perioperative TEs. Moreover, the study highlighted the impact of aneurysm characteristics, such as the dome-to-neck ratio and size, on perioperative complications. Wide-necked aneurysms, indicated by a dome-to-neck ratio < 2, were associated with lower rates of perioperative TEs, suggesting their suitability for stent-assisted embolization.
However, the study had limitations, including a small sample size in the DAPT group and potential biases associated with a single-center retrospective design. Additionally, the optimal dosing regimen for tirofiban requires further investigation.
In conclusion, the study underscores the effectiveness of combined arteriovenous tirofiban in preventing perioperative TEs during stent-assisted embolization for ruptured intracranial aneurysms, with no increased risk of HEs. Aneurysm characteristics, particularly the dome-to-neck ratio, may influence perioperative complications, emphasizing the importance of individualized treatment approaches. Further research is warranted to refine antiplatelet protocols and optimize patient outcomes in this setting.
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