Association between silent embolic cerebral infarction and continuous increase of P2Y12 reaction units after neurovascular stenting

Clinical article

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Object

Endovascular procedures are one of the important treatment options for steno-occlusive arteries in ischemic stroke patients. However, embolic complications after such procedures are always a concern. The authors investigated the association between serial change of residual platelet reactivity and silent embolic cerebral infarction (SECI) after endovascular treatment.

Methods

Ischemic stroke patients undergoing stenting of intra- or extracranial arteries were recruited prospectively. Residual platelet reactivity, represented by aspirin reaction units (ARUs) and P2Y12 reaction units (PRUs), was measured serially (6 hours before, immediately after, and 24 hours after the procedure). A loading dosage of aspirin (500 mg) and/or clopidogrel (300 mg) was given 24 hours before the procedure to patients naïve to antiplatelet agents, whereas the usual dosage (aspirin 100 mg and clopidogrel 75 mg) was continued for patients who had previously been taking these agents for more than a week. Diffusion-weighted MRI was performed before and 24 hours after the procedure to detect new SECIs. Clinical characteristics, baseline ARU and PRU values, and the change in ARU and PRU values after stenting were compared between patients with and without SECIs.

Results

Among 69 consecutive patients who underwent neurovascular stent insertion, 41 patients (59.4%) had poststenting SECIs. The lesion was located only at the vascular territory of the stented vessel in 21 patients (51.2%), outside the stented vessel territory in 8 patients (19.5%), and both inside and outside in 12 patients (29.3%). The occurrence of SECIs was not associated with the baseline ARU or PRU value, but was associated with PRU increase after stenting (36 ± 73 vs -12 ± 59, p = 0.007), deployment of a longer stent (31.1 ± 16.5 mm vs 21.8 ± 9.9 mm, p = 0.01), and stent insertion in extracranial arteries (78.1% vs 45.2%, p = 0.008). Stent length (OR 1.066, p = 0.01) and PRU change (OR 1.009, p = 0.04) were independently associated with the occurrence of SECI.

Conclusions

Residual platelet reactivity after dual antiplatelet treatment measured before stenting did not predict poststenting SECI. However, the longer stent and the serial increase of PRU values after stenting were related to SECI. Continuous increase of platelet activation after endovascular procedure may be important in poststent cerebral infarction.

Abbreviations used in this paper:ARU = aspirin reaction unit; DWI = diffusion-weighted imaging; ECAS = extracranial atherosclerotic stenosis; ICAS = intracranial atherosclerotic stenosis; PRU = P2Y12 reaction unit; SECI = silent embolic cerebral infarction.

Abstract

Object

Endovascular procedures are one of the important treatment options for steno-occlusive arteries in ischemic stroke patients. However, embolic complications after such procedures are always a concern. The authors investigated the association between serial change of residual platelet reactivity and silent embolic cerebral infarction (SECI) after endovascular treatment.

Methods

Ischemic stroke patients undergoing stenting of intra- or extracranial arteries were recruited prospectively. Residual platelet reactivity, represented by aspirin reaction units (ARUs) and P2Y12 reaction units (PRUs), was measured serially (6 hours before, immediately after, and 24 hours after the procedure). A loading dosage of aspirin (500 mg) and/or clopidogrel (300 mg) was given 24 hours before the procedure to patients naïve to antiplatelet agents, whereas the usual dosage (aspirin 100 mg and clopidogrel 75 mg) was continued for patients who had previously been taking these agents for more than a week. Diffusion-weighted MRI was performed before and 24 hours after the procedure to detect new SECIs. Clinical characteristics, baseline ARU and PRU values, and the change in ARU and PRU values after stenting were compared between patients with and without SECIs.

Results

Among 69 consecutive patients who underwent neurovascular stent insertion, 41 patients (59.4%) had poststenting SECIs. The lesion was located only at the vascular territory of the stented vessel in 21 patients (51.2%), outside the stented vessel territory in 8 patients (19.5%), and both inside and outside in 12 patients (29.3%). The occurrence of SECIs was not associated with the baseline ARU or PRU value, but was associated with PRU increase after stenting (36 ± 73 vs -12 ± 59, p = 0.007), deployment of a longer stent (31.1 ± 16.5 mm vs 21.8 ± 9.9 mm, p = 0.01), and stent insertion in extracranial arteries (78.1% vs 45.2%, p = 0.008). Stent length (OR 1.066, p = 0.01) and PRU change (OR 1.009, p = 0.04) were independently associated with the occurrence of SECI.

Conclusions

Residual platelet reactivity after dual antiplatelet treatment measured before stenting did not predict poststenting SECI. However, the longer stent and the serial increase of PRU values after stenting were related to SECI. Continuous increase of platelet activation after endovascular procedure may be important in poststent cerebral infarction.

Stenting of intra- or extracranial arteries with severe stenosis is likely to be effective for preventing subsequent ischemic stroke by improving cerebral perfusion and reducing the risk of thromboembolism by removing the plaque and eliminating turbulent flow. However, a recent large clinical trial failed to show a beneficial effect of intracranial stenting on secondary stroke prevention.9 Despite a low incidence of periprocedural myocardial infarction after carotid artery stenting, the prevalence of periprocedural stroke was higher than that in patients treated with carotid endarterectomy.6 High periprocedural risk of embolic stroke in intravascular procedures may limit the benefit of stenting for ischemic stroke patients.

The incidence of ischemic stroke after intracranial stenting has been found to be as high as 10.3%,12 and in one study, 21% of the patients treated with carotid artery stenting demonstrated poststenting silent embolic cerebral infarction (SECI).13 These silent ischemic lesions presented on diffusion-weighted imaging (DWI) may serve as a useful surrogate marker of clinical stroke occurring after cerebrovascular procedures.10 Although the technology that protects against thromboembolic complications has tried to enhance the safety of the stenting procedure,4,20 the risks posed by these hazardous complications remain a concern.

The importance of dual antiplatelet pretreatment with aspirin and clopidogrel cannot be overemphasized in neurovascular procedures.2 However, 1 of every 5 patients and 1 of every 2 patients who receive endovascular treatment demonstrate resistance to aspirin and clopidogrel, respectively.15,23,26 The residual platelet reactivity after antiplatelet therapy changes dynamically after stenting procedures.16 Therefore, in this study we evaluated the association between the change in residual platelet reactivity after dual antiplatelet treatment, measured by antiplatelet resistance, and the occurrence of SECI after stenting.

Methods

Study Population

Patients admitted to the Asan Medical Center for neurovascular stenting of supra-aortic intra- or extracranial arteries between September 2010 and December 2011 were prospectively included in the analysis. Patients aged more than 20 years old with a symptomatic stenosis causing ischemic stroke or transient ischemic attack (within 2 weeks from symptom onset) were included. All endovascular procedures were scheduled on an elective basis. We excluded patients who were 1) receiving emergency procedures in the hyperacute period (within 24 hours from symptom onset); 2) receiving additional procedure such as coiling; 3) were treated for conditions diagnosed as cerebral dissection or vasculitis; or 4) did not take aspirin and/or clopidogrel in accordance with the protocol detailed below. However, ischemic stroke patients undergoing stent insertion as a scheduled procedure during the acute stage (within 7 days from symptom onset) according to the study protocol, after the administration of antiplatelet agents, were enrolled.

Demographic features and vascular risk factors (hypertension, diabetes, hyperlipidemia, and previous stroke history) were obtained for enrolled patients. Routine laboratory tests, including complete blood cell counts and assessment of fibrinogen and C-reactive protein levels, were performed 1 day before the procedure. DWI and measurements of residual platelet reactivity were performed before and after stenting as detailed below. This study was approved by the institutional review board of Asan Medical Center. Written informed consent was obtained from all study participants or their legal representatives.

Premedication and the Extent of Platelet Inhibition

Aspirin and clopidogrel were administered at least 1 day before stenting. Loading doses of antiplatelet agents were administered (aspirin 500 mg and clopidogrel 300 mg) to patients who were naïve to antiplatelet treatment, except for those with a high possibility of bleeding complications. The usual maintenance dosages of aspirin (100 mg per day) and clopidogrel (75 mg per day) were administered to patients who had previously been taking these antiplatelet agents. The maintenance dosage was administered for more than 1 week prior to the procedure. The extent of platelet inhibition by antiplatelet agents was measured using the VerifyNow aspirin and VerifyNow P2Y12 assays (Accumetrics). Aspirin reaction units (ARUs) were measured twice, within 6 hours before the procedure (baseline) and at 24 hours after the procedure (follow-up). P2Y12 reaction units (PRUs) were measured 3 times: at baseline, immediately after the procedure, and at 24 hours' follow-up. Results were expressed as ARUs, PRUs, and the percentage of platelet inhibition (% PI). An ARU value ≥ 5508 and a PRU value ≥ 275,22 which have been shown to predict the clinical events more appropriately in this patient population, were defined as resistance to aspirin and clopidogrel, respectively.

MRI and Stenting Procedures

A baseline DWI study was performed within 1 week before the procedure with a 1.5-T MR system (GE Medical Systems) with a standard neurovascular coil. The study was repeated 24 hours after stent insertion. The locations of newly developed SECIs were analyzed. The extent of atherosclerosis was determined by the number of cerebral arteries with significant steno-occlusions (> 50%) and the degree of stenosis on angiography. All image analysis was performed by a stroke neurologist (J.Y.K.) blinded to all the clinical data.

The endovascular procedure was performed under monitored anesthesia by a well-established neurointerventionist. Most of the procedures were performed via femoral artery approach, although in 3 cases the approach was from the right radial artery. For extracranial artery stenting, distal anti-embolic devices were used in most cases (81.8%, 27 of 33). Stent insertion was performed using the Wingspan (Boston Scientific) stent for intracranial arteries, whereas most of the extracranial arteries were stented with open-cell stents such as Precise (Cordis), Acculink (Abbott Vascular), and Protégé (Covidien). Only 1 patient was treated with a closed-cell stent—a Wallstent (Boston Scientific). During the endovascular procedure, patients received 2000 to 5000 IU of intravenous heparin to attain an activated clotting time of approximately 200 seconds or 2-fold higher than baseline. The total procedure time, total dose of heparin, number of stents inserted, diameter and total length of the stent, maximum pressure during ballooning, and site of stent placement were recorded.

Data Analysis

Demographic variables, conventional risk factors, factors related to the procedures, laboratory results, loading of antiplatelet agents, and atherosclerosis status were compared between patients with and without SECI after neurovascular stenting. A chi-square test and Student t-test were used for numerical and categorical variables, as appropriate. Factors with potential association with SECI (p < 0.20) from the univariate logistic regression analysis were entered into the multivariate model. A 2-tailed p value < 0.05 was considered statistically significant. All statistical analyses were performed with SPSS for Windows software (version 17.0; SPSS).

Results

Sixty-nine patients were included according to the predetermined criteria. All the patients underwent MRI before and after stenting. The mean age of the patients was 63.2 years, and 77% were male. Fifty-three patients (77%) presented with cerebral infarction, whereas the remaining 16 patients (23%) had transient ischemic attacks. The majority of the patients (87.0%) received 1 stent, 8 patients received 2 stents, and 1 patient received 3. Stents were inserted in the internal carotid (42 stents [53.2%]), vertebral (18 stents [22.8%]), middle cerebral (14 stents [17.7%]), basilar (4 stents [5.1%]), and common carotid (1 stent [1.3%]) arteries.

In 41 patients (59.4%) SECI was identified as a new lesion on a follow-up DWI (+SECI group). The lesion was located only at the vascular territory of the stented vessel in 21 patients (51.2%), whereas in 8 patients (19.5%) DWI demonstrated a lesion outside the territory of the stented vessel. The remaining 12 patients (29.3%) had lesions both inside and outside the vascular territory of the stented vessel.

Comparison of Patients With and Without SECI After Stenting

There were no differences found in terms of risk factors between the patients in the +SECI group and patients without SECI (–SECI group; Table 1). SECI was more frequently observed in female patients. The total procedure time and the total amount of heparin used during the procedure, which reflect the technical difficulty of the stenting, were similar in the 2 groups. However, SECI was more frequently observed after stenting for extracranial atherosclerotic stenosis (ECAS) than after stenting for intracranial atherosclerotic stenosis (ICAS). Of the patients who received stenting for ICAS, 43.2% (16 of 37 patients) demonstrated poststenting SECI, whereas 81.5% (22 of 27 patients) and 60.0% (3 of 5 patients) showed SECI after stenting for ECAS and tandem lesions, respectively. The total length of the stent inserted was significantly longer in the +SECI group (mean 31.1 ± 16.5 mm vs 21.8 ± 9.9 mm, p = 0.01).

TABLE 1:

Comparison of demographics and clinical variables between patients with and without SECI*

Variable+SECI (n = 41)−SECI (n = 28)p Value
demographics
 age (yrs)64.2 ± 10.061.8 ± 10.7 
 male28 (68.3)25 (89.3) 
presentation 
 infarction3023
 TIA115
risk factors
 hypertension31 (75.6)19 (70.4) 
 diabetes mellitus22 (53.7)12 (42.9) 
 hyperlipidemia28 (68.3)14 (51.9) 
 cigarette smoking22 (53.6)16 (57.2) 
 previous stroke history13 (31.7)5 (17.9) 
procedure-related factors
 size of sheath (Fr)7.2 ± 1.47.0 ± 1.3 
 total procedure time (minutes)107.3 ± 33.6113.6 ± 45.5 
 total heparin dose (IU)4035 ± 16193696 ± 1302 
 no. of stents used1.15 ± 0.361.11 ± 0.42 
 max diameter of stent (mm)5.48 ± 2.134.48 ± 1.79 
 total length of stent (mm)31.1 ± 16.521.8 ± 9.9 
 site of stenting 
  ECAS225
  ICAS1621
  tandem32
 max pressure for ballooning (atm)9.9 ± 2.710.1 ± 3.2 
laboratory results
 WBC count (cells/mm3)6688 ± 15977321 ± 1970 
 hemoglobin (mg/dl)13.9 ± 1.914.1 ± 1.7 
 platelet count (× 1000/mm3)239 ± 55226 ± 60 
 C-reactive protein (mg/dl)0.42 ± 0.730.80 ± 1.71 
 fibrinogen (mg/dl)298 ± 63310 ± 81 
antiplatelet agents
 loading of aspirin11 (26.8)9 (32.1) 
 loading of clopidogrel5 (12.2)7 (25.0) 
 additional cilostazol4 (9.8)3 (10.7) 
status of atherosclerosis
 degree of stenosis (%)81.3 ± 8.383.3 ± 10.2 
 atherosclerotic steno-occlusions of other supra-aortic arteries25 (61.0)16 (57.1) 
 no. of steno-occlusions of other supra-aortic arteries1.10 ± 1.100.83 ± 1.10 

Results are expressed as number (%) or mean ± SD. TIA = transient ischemic attack; WBC = white blood cell.

Extent of Platelet Inhibition and SECI

The baseline ARU and PRU values before stenting were not statistically different between the +SECI and –SECI groups. None of the patients received medications known to influence ARU or PRU values (proton pump inhibitors or nonsteroidal antiinflammatory drugs). Only 2 patients (2.9%) demonstrated aspirin resistance, and only 9 (13.1%) demonstrated clopidogrel resistance at baseline, and there were no differences found between the 2 groups. Among the 9 patients with clopidogrel resistance, 7 patients received additional cilostazol after consideration of the potential benefit of preventing a thrombotic event. Immediately after stent placement, the PRU value increased by 35.3 ± 66.4 in the +SECI group and by 4.7 ± 73.0 in the –SECI group. However, this difference was not statistically significant (p = 0.08).

One day after stent placement, there was no difference found in terms of the ARU or PRU values between the +SECI and –SECI groups (ARU: 420 ± 49 vs 437 ± 85, p = 0.35; and PRU: 224 ± 70 vs 207 ± 76, p = 0.36). There was also no significant change in the ARU values following neurovascular stenting. However, the PRU significantly increased (36 ± 73) in patients with SECI after stenting, whereas it decreased (−12 ± 59) in patients without SECI (p = 0.007; Fig. 1). In addition, the number of patients with clopidogrel resistance also increased after stenting in the +SECI group (from 12.2% to 26.8%), whereas there was no increase in the –SECI group (Table 2). The mean PRU value in patients with SECI showed a continuous increase after stenting, whereas in patients without SECI, the PRU value reactively increased immediately after stent insertion, but decreased at the 24 hours' follow-up (Fig. 2).

Fig. 1.
Fig. 1.

The difference in residual platelet reactivity (ARU, upper, and PRU, lower) between baseline and 24 hours after stroke. The frequency of increased PRU levels after stenting was higher in patients with SECI (blue) than without (green).

TABLE 2:

Extent of platelet inhibition before and after stenting*

Variable+SECI (n = 41)−SECI (n = 28)p Value
baseline (before stenting)
 ARU421 ± 45438 ± 750.29
 ARU ≥5500 (0)2 (7.1)0.09
 PRU188 ± 70214 ± 680.12
 % PI (%)30 ± 2227 ± 190.53
 PRU ≥2755 (12.2)4 (14.3)0.80
immediately after stenting
 PRU218 ± 72219 ± 730.97
 % PI (%)33 ± 2422 ± 170.05
 PRU ≥27512 (31.6)5 (18.5)0.24
24 hrs after stenting
 ARU420 ± 49437 ± 850.35
 ARU ≥5501 (2.4)3 (11.1)0.30
 PRU224 ± 70207 ± 760.36
 % PI (%)30 ± 2126 ± 230.42
 PRU ≥27511 (26.8)4 (14.3)0.25
change btwn baseline & 24 hrs after stenting
 ARU1.1 ± 53−0.5 ± 800.92
 PRU36 ± 73−12 ± 590.007
 % PI (%)0.4 ± 20−0.5 ± 210.88

Results are expressed as number (%) or mean ± SD. % PI = percent platelet inhibition.

Fig. 2.
Fig. 2.

Serial changes in residual platelet reactivity before, immediately after, and 24 hours after stenting. PRU levels showed a continued increase 24 hours after stent insertion in patients with SECI (blue), whereas in patients without SECI (green), PRU levels decreased following an immediate postprocedural transient increase.

Independent Predictors of SECI After Neurovascular Stenting

According to the results of univariate binary logistic regression analysis, sex, the site of stent insertion, total length of the stent, and PRU value change between baseline and 24 hours after the procedure were entered into the multivariate analysis. The results showed that the total length of the stent inserted and the change in the PRU value after stenting were independently associated with the occurrence of SECI after neurovascular stenting after adjustment (Table 3). However, the site of stenting lost its significant association with SECI occurrence in this model.

TABLE 3:

Independent risk factors for SECI after neurovascular stenting*

VariableOR (95% CI)p ValueAdjusted ORAdjusted p Value
age1.024 (0.976–1.073)0.34
male0.258 (0.066–1.013)0.05
presentation (infarction)0.593 (0.181–1.946)0.39
hypertension1.240 (0.418–3.675)0.70
diabetes1.544 (0.586–4.064)0.38
hyperlipidemia2.000 (0.735–5.444)0.18
smoking0.868 (0.272–2.778)0.81
total procedure time0.996 (0.983–1.008)0.48
total heparin dose1.000 (1.000–1.000)0.32
total length of stent1.057 (1.011–1.105)0.011.066 (1.014–1.122)0.01
stented site
 ICAS1.000
 ECAS4.583 (1.500–14.001)0.008
 tandem1.875 (0.279–12.613)0.52
WBC count1.000 (1.000–1.000)0.15
PRU change after stenting1.011 (1.003–1.019)0.011.009 (1.001–1.018)0.04

Adjusted OR and p value represent the results of multivariate logistic regression analysis. Variables with potential association (p < 0.20) were entered to the multivariate logistic regression analysis.

Discussion

The aim of this study was to evaluate the association between the change of residual platelet reactivity after dual antiplatelet treatment and the occurrence of SECI after stenting. The occurrence of SECI was found not to be associated with the baseline ARU or PRU values measured prior to stenting. However, patients with increasing PRU values 24 hours after stenting compared with baseline demonstrated a higher probability of SECI. The total length of the stent inserted was also associated with the occurrence of SECI.

In our previous study, we found that SECI after coronary angiography was closely associated with the responsiveness to antiplatelet agents that was measured before the endovascular procedures.14 In contrast, our present results show that the baseline ARU and PRU values are not associated with SECI after stenting in supra-aortic intra- or extracranial arteries. During coronary angiography, the catheter is primarily located at the aortic arch, where the coronary arteries originate, and the procedure itself is static. In contrast, neurovascular stenting requires more manipulations, such as frequent switching of the instruments and the passage of the wire or stenting devices through the arteries with heavy atherosclerosis burdens. SECI after neurovascular stenting was found in our analysis to be associated with the total length of the stent inserted and the continuous increase of PRU after stent insertion. Foreign materials inside the vascular space are known to be thrombogenic.5,28 Compared with coronary angiography, where the catheter is removed immediately after the procedure, in neurovascular stenting, the stent is permanently inserted inside the vascular wall, and it may increase the platelet reactivity, even after the procedure is completed. Therefore, the inserted stent can cause poststenting thromboembolic events, and those patients with increasing PRU values may be prone to embolic events until the inserted stent is stabilized.

Periprocedural embolic events following neurovascular stenting can have various etiologies. First, the approach of the wires or the stents to the target site can cause embolic events by dislodging thrombi from the atherosclerotic vessels.7 Second, during the stent deployment, the plaque may be cracked and dislodged and may migrate to distal cerebral vessels.3,27 Finally, the inserted stent can cause embolism until stabilization.18 Nearly half of the patients in our present study presented with SECI outside of the vascular territory of the stented vessel, and these lesions can be explained by the dislodgement of atheroma that arose during multiple switching and approaches of wires and stents through the more proximal sites (for example, the aortic arch). Previous studies have demonstrated that the nature of the plaque (surface irregularity and high lipid content) is closely associated with the microembolic signals during the procedure.3,27 Our current results also demonstrate that the length of the stent, which represents the atherosclerotic burden of the stented site, is associated with the occurrence of SECI. Therefore, the dislodgement of atheroma from the plaque seems to be one of the most important mechanisms involved in SECI occurrence. However, the longer length of the stent does not only present a higher possibility of atheroma dislodgement, it may also induce a larger extent of endothelial injury and release prothrombotic material from the arterial wall and, therefore, cause thromboembolism. High residual platelet activity may potentiate this process.

In a previous study, SECI was observed in only 9% of patients at 1 hour after stenting, compared with 78% at 48 hours after the procedure.25 Microembolic signals were also detected after the stent insertion. Our present results demonstrate that the increase in PRU level after stenting is independently predictive of SECI. These findings may highlight the importance of embolisms that occur after stent insertion and removal of the catheter. Though the dislodgement of atheroma during stenting is important, various devices are used to protect against embolic barrage during this period. However, after the catheter is removed, protection by such devices is impossible. Therefore, the response to antiplatelet agents is critical during this period. As the baseline residual platelet reactivity did not show a significant difference, our study has limitations stemming from the clinical significance. However, our results may help understanding the various causes of cerebral infarction occurring after neurovascular stenting. Especially, the importance of platelet inhibition after stent insertion can be emphasized by our result. Interestingly, only the increase of PRU level (not ARU level) after stenting was associated with the occurrence of SECI. In previous studies, P2Y12 inhibitor resistance was associated with a high rate of adverse events after neurovascular stenting11,21 A high PRU level after coronary intervention was also associated with poor prognosis.24 P2Y12 receptors are critical to the generation of irreversible aggregation through the thromboxane A2–dependent pathway.1 Therefore, the increase in PRU level may be more important for predicting thromboembolic complication after endovascular treatment. Although the values after stenting did not reach the definition of antiplatelet resistance, as the values represent the reactivity of platelets, continuous increase of residual platelet reactivity is associated with the occurrence of embolic events.

There are some noteworthy limitations to our present study. First, the sample size was small. Second, there was heterogeneity with respect to the location of stent placement, and the nature of plaque in ICAS and ECAS may differ. The small sample size limited subanalysis with stratification for ICAS and ECAS. However, the trend of PRU level change according to the occurrence of SECI was similar in both ICAS and ECAS stenting (data not shown). Although, our study represents the result of neurovascular stenting overall, further study comparing the change in residual platelet reactivity after stenting ICAS and ECAS is needed. Third, we could not compare the clinical events because of their low incidence. Although SECIs are associated with reduced cognitive function17 and are widely used as a surrogate, the pathophysiology and the association with residual platelet reactivity may be different from that of symptomatic embolic infarctions. Fourth, no long-term follow-up data are presented. Because the levels of resistance to antiplatelet agents are associated with restenosis,19 follow-up data evaluated using ultrasonography at the stented area could have strengthened our results. Fifth, the change of PRU level after 24 hours was not documented. The study was initially designed to measure PRU levels until 24 hours after procedure. However, as our results show that PRU levels demonstrated a continuous increase, further study, with PRU levels obtained over a longer followup period, will be needed.

Conclusions

In conclusion, SECI after neurovascular stenting is associated with longer stent length and continuous increase of PRU levels after stent placement. Deploying a long stent may continuously activate platelets during and after the procedure and increase the poststenting embolic risk. Therefore, caution and close observation is needed for these patients.

Disclosure

This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI10C2020).

Author contributions to the study and manuscript preparation include the following. Conception and design: all authors. Acquisition of data: BJ Kim, JY Kwon, Jung. Analysis and interpretation of data: SU Kwon, BJ Kim, JY Kwon, Kang, JS Kim. Drafting the article: BJ Kim, Kang. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: SU Kwon. Statistical analysis: BJ Kim. Study supervision: SU Kwon, JY Kwon, Jung, Kang, JS Kim.

This article contains some figures that are displayed in color online but in black-and-white in the print edition.

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    Matetzky SShenkman BGuetta VShechter MBeinart RGoldenberg I: Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 109:317131752004. (Erratum in Circulation 124: e459 2011)

  • 20

    Matsumura JSGray WChaturvedi SYamanouchi DPeng LVerta P: Results of carotid artery stenting with distal embolic protection with improved systems: Protected Carotid Artery Stenting in Patients at High Risk for Carotid Endarterectomy (PROTECT) trial. J Vasc Surg 55:968976.e52012

  • 21

    Müller-Schunk SLinn JPeters NSpannagl MDeisenberg MBrückmann H: Monitoring of clopidogrel-related platelet inhibition: correlation of nonresponse with clinical outcome in supra-aortic stenting. AJNR Am J Neuroradiol 29:7867912008

  • 22

    Park KWPark JJJeon KHKang SHOh IYYang HM: Clinical predictors of high posttreatment platelet reactivity to clopidogrel in Koreans. Cardiovasc Ther 30:5112012

  • 23

    Prabhakaran SWells KRLee VHFlaherty CALopes DK: Prevalence and risk factors for aspirin and clopidogrel resistance in cerebrovascular stenting. AJNR Am J Neuroradiol 29:2812852008

  • 24

    Price MJEndemann SGollapudi RRValencia RStinis CTLevisay JP: Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation. Eur Heart J 29:99210002008

  • 25

    Rapp JHWakil LSawhney RPan XMYenari MAGlastonbury C: Subclinical embolization after carotid artery stenting: new lesions on diffusion-weighted magnetic resonance imaging occur postprocedure. J Vasc Surg 45:8678742007

  • 26

    Reavey-Cantwell JFFox WCReichwage BDFautheree GLVelat GJWhiting JH: Factors associated with aspirin resistance in patients premedicated with aspirin and clopidogrel for endovascular neurosurgery. Neurosurgery 64:8908962009

  • 27

    Rosenkranz MRussjan AGoebell EHavemeister SThomalla GCheng B: Carotid plaque surface irregularity predicts cerebral embolism during carotid artery stenting. Cerebrovasc Dis 32:1631692011

  • 28

    Tschoepe DSchultheiss HPKolarov PSchwippert BDannehl KNieuwenhuis HK: Platelet membrane activation markers are predictive for increased risk of acute ischemic events after PTCA. Circulation 88:37421993

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Article Information

Address correspondence to: Sun U. Kwon, M.D., Ph.D., Stroke Center and Department of Neurology, Asan Medical Center, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736, Korea. email: sukwon@amc.seoul.kr.

Please include this information when citing this paper: published online July 18, 2014; DOI: 10.3171/2014.6.JNS132448.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    The difference in residual platelet reactivity (ARU, upper, and PRU, lower) between baseline and 24 hours after stroke. The frequency of increased PRU levels after stenting was higher in patients with SECI (blue) than without (green).

  • View in gallery

    Serial changes in residual platelet reactivity before, immediately after, and 24 hours after stenting. PRU levels showed a continued increase 24 hours after stent insertion in patients with SECI (blue), whereas in patients without SECI (green), PRU levels decreased following an immediate postprocedural transient increase.

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20

Matsumura JSGray WChaturvedi SYamanouchi DPeng LVerta P: Results of carotid artery stenting with distal embolic protection with improved systems: Protected Carotid Artery Stenting in Patients at High Risk for Carotid Endarterectomy (PROTECT) trial. J Vasc Surg 55:968976.e52012

21

Müller-Schunk SLinn JPeters NSpannagl MDeisenberg MBrückmann H: Monitoring of clopidogrel-related platelet inhibition: correlation of nonresponse with clinical outcome in supra-aortic stenting. AJNR Am J Neuroradiol 29:7867912008

22

Park KWPark JJJeon KHKang SHOh IYYang HM: Clinical predictors of high posttreatment platelet reactivity to clopidogrel in Koreans. Cardiovasc Ther 30:5112012

23

Prabhakaran SWells KRLee VHFlaherty CALopes DK: Prevalence and risk factors for aspirin and clopidogrel resistance in cerebrovascular stenting. AJNR Am J Neuroradiol 29:2812852008

24

Price MJEndemann SGollapudi RRValencia RStinis CTLevisay JP: Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation. Eur Heart J 29:99210002008

25

Rapp JHWakil LSawhney RPan XMYenari MAGlastonbury C: Subclinical embolization after carotid artery stenting: new lesions on diffusion-weighted magnetic resonance imaging occur postprocedure. J Vasc Surg 45:8678742007

26

Reavey-Cantwell JFFox WCReichwage BDFautheree GLVelat GJWhiting JH: Factors associated with aspirin resistance in patients premedicated with aspirin and clopidogrel for endovascular neurosurgery. Neurosurgery 64:8908962009

27

Rosenkranz MRussjan AGoebell EHavemeister SThomalla GCheng B: Carotid plaque surface irregularity predicts cerebral embolism during carotid artery stenting. Cerebrovasc Dis 32:1631692011

28

Tschoepe DSchultheiss HPKolarov PSchwippert BDannehl KNieuwenhuis HK: Platelet membrane activation markers are predictive for increased risk of acute ischemic events after PTCA. Circulation 88:37421993

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