Treatment after stent placement to correct CVSS-induced severe intracranial hypertension is an important step
CVSS mainly involves the transverse sinus and the junction of the transverse sinus and sigmoid sinus, resulting in severe intracranial hypertension (ICP). Our results are consistent with other studies that demonstrated that stenting is an effective method for CVSS-induced severe intracranial hypertension correction [
9,
18]. Although the MPG decreased poststenting, cerebral venous blood flow was restored, and the ICP was corrected immediately poststent management, which is still important for long-term favorable outcomes, and adequate treatment strategies are urgently needed [
11,
19,
20].
OACs plus antiplatelet therapy may be better than dual antiplatelet therapy for poststenting
There are no current guidelines about CVSS poststenting management. Some studies opted for aspirin plus clopidogrel 3–5 days prior to and 3–6 months poststenting, referring to the management in arterial disease [
21‐
23]. One study used only clopidogrel as a poststenting treatment agent, and another three studies used oral warfarin for 8 weeks followed by a substitution to aspirin for 6 months or longer [
10,
12,
13,
24]. There were several adverse events, such as in-stent thrombosis, in the studies using dual antiplatelet therapy for 3–6 months poststenting [
21‐
23]. However, emulating the same treatment of arterial diseases may not be suitable because the venous internal environment differs when comparing atherosclerotic plaques in the vessel wall, blood components, and fit of the stent to the vessel wall [
25]. Teleb et al. summarized 19 studies and noted that 2 out of 207 patients developed intrastent thrombosis. Fortunately, these patients achieved complete revascularization with adequate anticoagulation [
26]. Our previous study revealed that the majority of patients with CVSS had a history of hypercoagulability, immune inflammation, thrombophilia, or thrombosis [
27]. Although stenting could correct the local stenosis immediately, it could not correct their systemic thrombophilia. Moreover, based on follow-up using magnetic resonance venous thrombosis black blood imaging studies, long-term anticoagulation might be needed in CVSS poststenting [
1‐
3]. Therefore, in this study, the duration of poststenting medical treatment was 1 year.
Previous studies have suggested that BMI is closely associated with idiopathic intracranial hypertension and may be a predictor of CVSS-related intracranial hypertension [
4,
8,
28]. This conclusion was also found in our study, with a high proportion of overweight women in both groups. Cerebral venous outflow retardation induced by increased BMI is also a factor for consideration, as it also differs from arterial poststenting.
On the other hand, as a foreign body, the stent could provoke platelet overactivation, making antiplatelet agents necessary for prevention. Furthermore, it is well known that venous thrombosis differs from arterial thrombosis: arterial thrombi are platelet-rich and gather around ruptured atherosclerotic plaques and endothelial damage, while venous thrombi are mainly comprised of abundant fibrin, red blood cells, and a limited number of activated platelets [
29]. Knowing this, antiplatelet therapy alone, as a strategy for venous thrombosis prevention poststenting, may not be enough. This information regarding the different pathological mechanisms of venous versus arterial thrombosis suggests that management for CVSS poststenting might differ from that for cerebral arterial poststenting management. Notably, this study suggests a lower rate of complications, especially restenosis, in both groups, which we speculate may be related to good patient compliance and an adequate course of treatment. However, more evidence is still needed for a more appropriate duration of treatment.
In this study, we compared the safety and efficacy of OACs plus single antiplatelet therapy with dual antiplatelet therapy and found that although there was no statistical significance between the two groups regarding bleeding events, venous thrombosis, intrastent thrombosis and other complications poststenting, there were still 2 cases of mild bleeding events, 1 case of intraluminal restenosis, and 2 cases of intrastent thrombosis in the dual antiplatelet group compared to none in the OAC plus antiplatelet group. Since there were no adverse events in the OAC plus single antiplatelet therapy group, OACs plus single antiplatelet therapy may have more promising effects; however, more evidence from a larger sample size is warranted to support this.
Safety and efficacy of NOACs versus warfarin on CVSS poststenting
Warfarin is a commonly used anticoagulant agent. However, the genetic heterogeneity of its individual pharmacokinetic response, interaction with numerous foods and drugs, and requirement of regularly monitoring the international normalized ratio (INR) limit its use in the clinical setting. NOACs could specifically block certain coagulation factors (such as dabigatran for thrombin or rivaroxaban for factor Xa), thereby inhibiting the conversion of fibrinogen to fibrin, and have been proven to be as efficacious as warfarin for anticoagulation in some cardiac diseases, such as atrial fibrillation [
30,
31]. A meta-analysis revealed that dabigatran was as efficacious as warfarin for preventing ischemic strokes in patients with nonvalvular atrial fibrillation and was associated with a lower risk of intracranial hemorrhage; however, it might promote gastrointestinal bleeding, especially in elderly individuals [
32]. However, in this study, the majority of patients were young and middle-aged (mean age 43.42 ± 13.23 years), and no gastrointestinal bleeding events were observed.
A multicenter randomized controlled study compared the safety and efficacy of dabigatran and warfarin in preventing venous thrombotic events in patients with CVT and found that both dabigatran and warfarin were associated with lower risks of CVT recurrence and bleeding [
16]. Consistent with previous studies, no bleeding events, venous thrombotic events, or stent-related complications were found in either the NOACs or warfarin groups, which suggested that NOACs may be as efficacious as warfarin for CVT control. The benefits of NOACs and the development of effective antagonists in recent years have led clinicians to favor NOACs [
33,
34]. Given that NOACs do not require frequent monitoring of coagulation markers, this also improves patient compliance. Moreover, antagonists for adverse bleeding events are already available. The new oral anticoagulants may be more favored by clinicians and patients in clinical settings. However, multicenter, randomized clinical trials are still needed to provide more robust evidence.
Limitations
First, this was only a single-center study. Multicenter studies with a large number of cases are still needed to further validate the conclusions. Second, the incidences of complications in CVSS poststenting were low in both groups, which might affect the assessment comparing OACs plus antiplatelet therapy and dual antiplatelet therapy. Another limitation in our study involved the choice to place patients with a higher risk of hypercoagulability in Group 1, thus making our two groups nonhomogeneous. In addition, we did not use genetic analysis for platelet drug resistance and could not assess whether it influenced the results. Our small sample size also failed to compare the differences among various NOACs. Another limitation was that the number of adverse events of stenting did not reach statistical significance. Finally, although the findings in this study provide a new reference for CVSS poststenting, long-term follow-up is still needed.