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Embolic protection devices during carotid artery stenting: Is there a difference between proximal occlusion and distal filter?
International Journal of Cardiology 187 (2015) 592–593
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Embolic protection devices during carotid artery stenting: Is there a difference between proximal occlusion and distal filter? Giuseppe Gargiulo 1, Eugenio Stabile 1, Anna Sannino, Cinzia Perrino, Bruno Trimarco, Giovanni Esposito ⁎ Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
a r t i c l e
i n f o
Article history: Received 30 March 2015 Accepted 31 March 2015 Available online 1 April 2015 Keywords: Carotid artery stenting Embolic protection Proximal occlusion Distal filter Diffusion-weighted magnetic resonance imaging
Dear Editor, Carotid artery stenting (CAS) is a validated treatment for patients with carotid artery stenosis to reduce the incidence of stroke. The use of embolic protection devices (EPDs) during CAS has demonstrated to reduce the incidence of peri-procedural ischemic events, however, the better EPD to use between proximal balloon occlusion and distal filter still remains debated. In a previous meta-analysis we compared the use of these two EPDs during CAS by evaluating the occurrence of new ischemic cerebral lesions detected with post-procedural diffusion-weighted magnetic resonance imaging (DW-MRI) [1]. We observed that CAS with proximal occlusion seemed to be associated with lower incidence of new ischemic cerebral lesions per patient and lower contralateral lesions compared to distal filter. In contrast, a more recent meta-analysis concluded that no significant differences exist between proximal and distal EPD [2]. The authors discussed that the previous conclusion was affected some limitations [2]. However, the following considerations are needed: a) the heterogeneity observed for the primary endpoint in our and their meta-analysis was similar (I2 = 70% and 68% respectively); b) it has not yet been clearly demonstrated that transcervical CAS
⁎ Corresponding author at: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy. E-mail address: [email protected] (G. Esposito). 1 The first two authors equally contributed to this work.
http://dx.doi.org/10.1016/j.ijcard.2015.03.435 0167-5273/© 2015 Published by Elsevier Ireland Ltd.
is associated to reduced cerebral embolization compared to the transfemoral approach. However, although we included a study using transcervical CAS with proximal occlusion [3], we also performed sensitivity analysis confirming the results [1]; c) we investigated on heterogeneity conducting both meta-regressions and sensitivity analyses and also publication bias was evaluated without observing significant results [1]; d) we preferred to not include post-operative clinical outcomes, particularly cumulative events (death/cerebrovascular events), because this message is still inconclusive and could be misleading for readers (the number of events is too small to support significant differences; the data analyzed are limited and restricted to the few studies included, while several other studies have investigated on the clinical impact of DW-MRI lesions), therefore, future larger studies will clarify the clinical short and long-term impacts of DW-MRI lesions (stroke, mortality, neurological symptoms, cognitive impairment, etc.); e) finally, despite the authors concluded that no significant differences were observed, their analysis shows a non-significant trend towards fewer new ischemic lesions with proximal occlusion compared to distal filter and it cannot be excluded that larger numbers could have obtained a sufficient statistical power. Therefore, in our opinion this result is insufficient to rule out a difference between the two strategies given the low number of overall patients analyzed. On the contrary, their result agrees more with ours and could be better interpreted according to our conclusion of provisional superiority of CAS with proximal occlusion over CAS with distal filter with the need for future large randomized trials to confirm this hypothesis. Here we show an updated meta-analysis in which a more recent large randomized study is pooled with our previous analyses [1,4]. Accordingly, studies published until March 2015 were included if comparing proximal occlusion and distal filter during CAS and if reporting data on new brain lesions detected with DW-MRI. The random-effects model was used to calculate odds ratio (OR) for the incidence of new cerebral lesions/patient and new contralateral lesions. According to our previous study, we observed that proximal occlusion was associated to fewer lesions/patient (9 studies, 451 patients; OR: 0.41, 95% confidence interval [CI] 0.21–0.80; P = 0.009; heterogeneity I2 = 71%; Fig. 1) and fewer contralateral lesions (8 studies, 416 patients; OR: 0.48, 95% CI 0.34– 0.69; P b 0.001; heterogeneity I2 = 0%; Fig. 1). The sensitivity analyses showed that no single study affected the pooled estimates of OR of the two endpoints with results being consistent even after removing a study at time (Table 1). In conclusion, we believe that the currently available data seem to support a better cerebral embolic protection with the proximal
G. Gargiulo et al. / International Journal of Cardiology 187 (2015) 592–593
593
Table 1 Sensitivity analyses. New lesions/patient
Akkaya et al. Bijuklic et al. Cano et al. Castro-Afonso et al. El-Koussy et al. Flach et al. Leal et al. Montorsi et al. Taha et al.
New contralateral lesions
Odds ratio [95% CI]
P value
Odds ratio [95% CI]
P value
0.46 [0.22–0.97] 0.47 [0.23–0.97] 0.41 [0.19–0.90] 0.31 [0.18–0.51] 0.42 [0.19–0.09] 0.34 [0.18–0.66] 0.42 [0.19–0.92] 0.41 [0.19–0.87] 0.45 [0.22–0.90]
0.042 0.040 0.027 b0.001 0.026 0.001 0.030 0.020 0.024
0.41 [0.27–0.61] 0.49 [0.33–0.74] 0.45 [0.31–0.67] 0.50 [0.34–0.73] 0.50 [0.34–0.74] 0.51 [0.35–0.74] 0.47 [0.31–0.71] – 0.51 [0.35–0.73]
b0.001 0.001 b0.001 b0.001 b0.001 b0.001 b0.001 – b0.001
Abbreviations: CI = confidence interval; OR = odds ratio.
Acknowledgments None.
References
Fig. 1. New DW-MRI cerebral lesions after CAS. Random effects odds ratio and 95% confidence interval for the endpoints of new ischemic lesions/patient and new contralateral lesions at DW-MRI after CAS.
occlusion than distal filter during CAS, however, this evidence is provisional and needs to be further confirmed in future larger studies. Conflict of interest None.
[1] E. Stabile, A. Sannino, G.G. Schiattarella, et al., Cerebral embolic lesions detected with diffusion-weighted magnetic resonance imaging following carotid artery stenting: a meta-analysis of 8 studies comparing filter cerebral protection and proximal balloon occlusion, JACC Cardiovasc. Interv. 7 (10) (2014) 1177–1183. [2] S. Cassese, G. Ndrepepa, L.A. King, et al., Proximal occlusion versus distal filter for cerebral protection during carotid stenting: updated meta-analysis of randomised and observational MRI studies, EuroIntervention 10 (12) (2015) (pii: 20140520-04). [3] I. Leal, A. Orgaz, A. Flores, et al., A diffusion-weighted magnetic resonance imagingbased study of transcervical carotid stenting with flow reversal versus transfemoral filter protection, J. Vasc. Surg. 56 (2012) 1585–1590. [4] E. Akkaya, E. Vuruskan, Z.B. Gul, et al., Cerebral microemboli and neurocognitive change after carotid artery stenting with different embolic protection devices, Int. J. Cardiol. 176 (2) (Sep 20 2014) 478–483.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Embolic protection devices during carotid artery stenting: Is there a difference between proximal occlusion and distal filter? Giuseppe Gargiulo 1, Eugenio Stabile 1, Anna Sannino, Cinzia Perrino, Bruno Trimarco, Giovanni Esposito ⁎ Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
a r t i c l e
i n f o
Article history: Received 30 March 2015 Accepted 31 March 2015 Available online 1 April 2015 Keywords: Carotid artery stenting Embolic protection Proximal occlusion Distal filter Diffusion-weighted magnetic resonance imaging
Dear Editor, Carotid artery stenting (CAS) is a validated treatment for patients with carotid artery stenosis to reduce the incidence of stroke. The use of embolic protection devices (EPDs) during CAS has demonstrated to reduce the incidence of peri-procedural ischemic events, however, the better EPD to use between proximal balloon occlusion and distal filter still remains debated. In a previous meta-analysis we compared the use of these two EPDs during CAS by evaluating the occurrence of new ischemic cerebral lesions detected with post-procedural diffusion-weighted magnetic resonance imaging (DW-MRI) [1]. We observed that CAS with proximal occlusion seemed to be associated with lower incidence of new ischemic cerebral lesions per patient and lower contralateral lesions compared to distal filter. In contrast, a more recent meta-analysis concluded that no significant differences exist between proximal and distal EPD [2]. The authors discussed that the previous conclusion was affected some limitations [2]. However, the following considerations are needed: a) the heterogeneity observed for the primary endpoint in our and their meta-analysis was similar (I2 = 70% and 68% respectively); b) it has not yet been clearly demonstrated that transcervical CAS
⁎ Corresponding author at: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy. E-mail address: [email protected] (G. Esposito). 1 The first two authors equally contributed to this work.
http://dx.doi.org/10.1016/j.ijcard.2015.03.435 0167-5273/© 2015 Published by Elsevier Ireland Ltd.
is associated to reduced cerebral embolization compared to the transfemoral approach. However, although we included a study using transcervical CAS with proximal occlusion [3], we also performed sensitivity analysis confirming the results [1]; c) we investigated on heterogeneity conducting both meta-regressions and sensitivity analyses and also publication bias was evaluated without observing significant results [1]; d) we preferred to not include post-operative clinical outcomes, particularly cumulative events (death/cerebrovascular events), because this message is still inconclusive and could be misleading for readers (the number of events is too small to support significant differences; the data analyzed are limited and restricted to the few studies included, while several other studies have investigated on the clinical impact of DW-MRI lesions), therefore, future larger studies will clarify the clinical short and long-term impacts of DW-MRI lesions (stroke, mortality, neurological symptoms, cognitive impairment, etc.); e) finally, despite the authors concluded that no significant differences were observed, their analysis shows a non-significant trend towards fewer new ischemic lesions with proximal occlusion compared to distal filter and it cannot be excluded that larger numbers could have obtained a sufficient statistical power. Therefore, in our opinion this result is insufficient to rule out a difference between the two strategies given the low number of overall patients analyzed. On the contrary, their result agrees more with ours and could be better interpreted according to our conclusion of provisional superiority of CAS with proximal occlusion over CAS with distal filter with the need for future large randomized trials to confirm this hypothesis. Here we show an updated meta-analysis in which a more recent large randomized study is pooled with our previous analyses [1,4]. Accordingly, studies published until March 2015 were included if comparing proximal occlusion and distal filter during CAS and if reporting data on new brain lesions detected with DW-MRI. The random-effects model was used to calculate odds ratio (OR) for the incidence of new cerebral lesions/patient and new contralateral lesions. According to our previous study, we observed that proximal occlusion was associated to fewer lesions/patient (9 studies, 451 patients; OR: 0.41, 95% confidence interval [CI] 0.21–0.80; P = 0.009; heterogeneity I2 = 71%; Fig. 1) and fewer contralateral lesions (8 studies, 416 patients; OR: 0.48, 95% CI 0.34– 0.69; P b 0.001; heterogeneity I2 = 0%; Fig. 1). The sensitivity analyses showed that no single study affected the pooled estimates of OR of the two endpoints with results being consistent even after removing a study at time (Table 1). In conclusion, we believe that the currently available data seem to support a better cerebral embolic protection with the proximal
G. Gargiulo et al. / International Journal of Cardiology 187 (2015) 592–593
593
Table 1 Sensitivity analyses. New lesions/patient
Akkaya et al. Bijuklic et al. Cano et al. Castro-Afonso et al. El-Koussy et al. Flach et al. Leal et al. Montorsi et al. Taha et al.
New contralateral lesions
Odds ratio [95% CI]
P value
Odds ratio [95% CI]
P value
0.46 [0.22–0.97] 0.47 [0.23–0.97] 0.41 [0.19–0.90] 0.31 [0.18–0.51] 0.42 [0.19–0.09] 0.34 [0.18–0.66] 0.42 [0.19–0.92] 0.41 [0.19–0.87] 0.45 [0.22–0.90]
0.042 0.040 0.027 b0.001 0.026 0.001 0.030 0.020 0.024
0.41 [0.27–0.61] 0.49 [0.33–0.74] 0.45 [0.31–0.67] 0.50 [0.34–0.73] 0.50 [0.34–0.74] 0.51 [0.35–0.74] 0.47 [0.31–0.71] – 0.51 [0.35–0.73]
b0.001 0.001 b0.001 b0.001 b0.001 b0.001 b0.001 – b0.001
Abbreviations: CI = confidence interval; OR = odds ratio.
Acknowledgments None.
References
Fig. 1. New DW-MRI cerebral lesions after CAS. Random effects odds ratio and 95% confidence interval for the endpoints of new ischemic lesions/patient and new contralateral lesions at DW-MRI after CAS.
occlusion than distal filter during CAS, however, this evidence is provisional and needs to be further confirmed in future larger studies. Conflict of interest None.
[1] E. Stabile, A. Sannino, G.G. Schiattarella, et al., Cerebral embolic lesions detected with diffusion-weighted magnetic resonance imaging following carotid artery stenting: a meta-analysis of 8 studies comparing filter cerebral protection and proximal balloon occlusion, JACC Cardiovasc. Interv. 7 (10) (2014) 1177–1183. [2] S. Cassese, G. Ndrepepa, L.A. King, et al., Proximal occlusion versus distal filter for cerebral protection during carotid stenting: updated meta-analysis of randomised and observational MRI studies, EuroIntervention 10 (12) (2015) (pii: 20140520-04). [3] I. Leal, A. Orgaz, A. Flores, et al., A diffusion-weighted magnetic resonance imagingbased study of transcervical carotid stenting with flow reversal versus transfemoral filter protection, J. Vasc. Surg. 56 (2012) 1585–1590. [4] E. Akkaya, E. Vuruskan, Z.B. Gul, et al., Cerebral microemboli and neurocognitive change after carotid artery stenting with different embolic protection devices, Int. J. Cardiol. 176 (2) (Sep 20 2014) 478–483.