MT has been demonstrated to be able to revascularize occluded intracranial arteries and accelerate the recovery of AIS patients. However, it inevitably fails to achieve recanalization in approximately 20% of AIS patients , and early re-occlusion may occur, especially when endothelial damage occurs . Tirofiban, a glycoprotein IIb/IIIa antagonist with a short half-life, is suggested to avert the risks of thromboembolic complications and improve the reperfusion status of the microvasculature [13–15], especially for patients with severe in situ atherosclerotic stenosis and permanent stenting. However, evidence about patient selection and the treatment strategy for the different subgroups remains ambiguous.
Our finding that tirofiban was more associated with an increasingly favorable outcome in patients with NIHSS scores above 14 may demonstrate that the benefit of tirofiban was significantly better in patients with moderate or severe stroke. Although the underlying mechanism is unknown, a possible explanation is that patients with higher NIHSS are at an inherent higher risk for failure of recanalization . First, higher NIHSS scores were significantly correlated with poor collateral circulation, which suggests that blood flow is difficult to restore to the level of TICI 2B-3 [17, 18]. Nevertheless, robust collateral circulation is important for the prevention of thrombus augmentation, dissolution of the fragmented thrombus and increasing the concentration of local thrombolytic drugs . Second, patients with higher NIHSS scores are often accompanied by occlusion of proximal large vessels with larger thrombi [20–22], which is more difficult to remove than patients with smaller thrombi. Therefore, we assume that tirofiban can give exert optimal advantages in patients with moderate and severe stroke who may benefit more from the increasing recanalization rate [23, 24]. In our study, the recanalization rate in the tirofiban group was lower than that in the control group (89.6% vs. 92.4%, P = 0.521), which is consistent with the results from previous studies wherein tirofiban did not increase the recanalization rate . This may be explained by the fact that tirofiban was prone to be used in patients with a high possibility of reocclusion, and not all of them were recanalized after tirofiban or other rescue strategies, such as intra-arterial thrombolysis and angioplasty. The recanalization rate defined as TICI 2b-3 only showed the final outcome, and the potential benefit of promoting recanalization needs further study.
Based on the findings of our study, the effect of tirofiban was not significantly modified by age, sex, ASPECTS, time from onset to puncture, use of t-PA or stroke etiology, which provided further support for the benefit of tirofiban in AIS patients, regardless of the baseline characteristics. Previous studies suggest that tirofiban is more effective in LAA patients than in CE patients . Our results also demonstrated similar indications that the association between tirofiban and clinical outcome was significant in LAA patients (aOR 1.91, 95% CI 1.88 ~ 4.15) but not in the other two groups. This finding is expected when atherosclerotic occlusion may complicate reperfusion, and re-occlusion can easily occur even after successful recanalization by in situ formation of microthrombus, conditions more likely to require antiplatelet therapy such as tirofiban. The crucial effect of time has been emphasized in relation to endovascular therapies for AIS patients . Both OTP time and OTR time influenced the outcome, and we performed subgroup analysis according to the OTP time, which occurs before MT and may be considered when operators make decisions about the administration of tirofiban . However, our study did not show heterogeneity in the subgroups according to OTP time, and large-sample size studies might be needed for further verification. Additionally, it should be taken into account that in the retrospective study, the OTP time of patients was based on the medical records derived from statements of patients and their family members, which was likely inaccurate and unreliable.
In safety-related analyses, tirofiban also did not increase the risk of bleeding in either the overall group or the subgroup, which was consistent with most studies and meta-analyses . However, Lars Keller et al., showed that additional treatment with tirofiban was associated with an increased risk of fatal intracerebral hemorrhage. Possible underlying causes of this result are that the enrolled patients were treated before 2011 with relatively unadvanced thrombectomy devices which achieved a low recanalization rate (61.1%). Given that tirofiban has a short half-life and rapid drug metabolism, tirofiban may be safe for selected patients.
These results further support the effect and safety of tirofiban in AIS patients and provide the notion that the effect of tirofiban may be modified by patient characteristics, helping inform clinical practice for more individualized decision-making in this subgroup. Of note, the use of rescue tirofiban was determined mainly according to individual arterial status and lesion characteristics, especially whether high-grade in situ atherosclerosis or endothelial damage by multiple stent passes occurred during MT. This study indicated that tirofiban may be more beneficial for patients with moderate and severe stroke, and patient characteristics, such as NIHSS score, could be taken into consideration as appropriate when making a decision on the administration of tirofiban.
Our study has several limitations. First, this was a retrospective study and has a risk of selection bias. We adjusted for potential confounders through the multivariable logistic regression model and obtained the same results. Second, these post hoc subgroup analyses may lack power, and the findings may have been accidental. A more detailed subgroup analysis according to NIHSS score was not performed due to the small sample size. Finally, other prognostic factors, such as collateral status, specific location of infarction, and remaining penumbral tissue, were not included in this study, which was potential confounders. The underlying mechanisms of tirofiban in AIS need further investigation, and prospective clinical trials are still needed to provide higher-level evidence.