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JNNP Online First, published on May 18, 2015 as 10.1136/jnnp-2014-310250 Cerebrovascular disease
RESEARCH PAPER
Outcomes of stent retriever thrombectomy in basilar artery occlusion: an observational study and systematic review Benjamin Gory,1 Islam Eldesouky,1 Rotem Sivan-Hoffmann,1 Murielle Rabilloud,2 Elodie Ong,3 Roberto Riva,1 Dorin Nicolae Gherasim,1 Alexis Turjman,1 Norbert Nighoghossian,3 Francis Turjman1 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ jnnp-2014-310250). 1
Department of Interventional Neuroradiology, Hôpital Neurologique Pierre Wertheimer, Bron, France 2 Department of Biostatitics, UMR 5558, Hospices Civils de Lyon, Lyon, France 3 Department of Neurology, Stroke Unit, Hôpital Neurologique Pierre Wertheimer, Bron, France Correspondence to Dr Benjamin Gory, Department of Interventional Neuroradiology, Hôpital Neurologique Pierre Wertheimer, 59 Boulevard Pinel, Bron 69677, France; [email protected] Received 26 December 2014 Revised 13 March 2015 Accepted 8 April 2015
ABSTRACT Background Basilar artery occlusion (BAO) remains one of the most devastating subtypes of stroke with high mortality and poor outcome. Early recanalisation is the most powerful predictor of favourable outcome in patients with stroke, and may be improved with mechanical thrombectomy using stent retriever devices. However, the benefit in functional outcome and safety of stent retrievers are not yet well known. The aim of this study was to assess efficacy and safety profiles of stent retriever thrombectomy in BAO patients with stroke. Methods We analysed data retrospectively from our consecutive clinical series and conducted a systematic review and meta-analysis of all previous studies of stent retriever thrombectomy in BAO patients with stroke between November 2010 and April 2014. Results From March 2010 to March 2013, 22 patients with acute BAO were treated with a Solitaire stent retriever in our series. Favourable outcome was significantly associated with younger age and distal BAO. The literature search identified 15 previous studies involving a total of 312 subjects. In the meta-analysis, including our series data, the recanalisation rate (Thrombolysis In Cerebral Infarction (TICI) score ≥2b) reached 81% (95% CI 73% to 87%). The rate of symptomatic intracranial haemorrhage was 4% (95% CI 2% to 8%), favourable outcome (modified Rankin Scale (mRS) ≤2 at 3 months) was found in 42% (95% CI 36% to 48%) and mortality rate was 30% (95% CI 25% to 36%). Conclusions Stent retriever thrombectomy is a safe treatment modality for patients with stroke presenting with BAO. Although the stent retrievers showed a good recanalisation rate, there are currently no randomised clinical trials to assess its clinical efficacy in comparison with the reference treatment. INTRODUCTION
To cite: Gory B, Eldesouky I, SivanHoffmann R, et al. J Neurol Neurosurg Psychiatry Published Online First: [please include Day Month Year] doi:10.1136/jnnp2014-310250
Strokes secondary to acute basilar artery occlusion (BAO) are associated with high mortality and poor outcome.1 2 Early recanalisation has been demonstrated to be the major goal of acute ischaemic stroke therapy.3–5 Although intravenous recombinant tissue plasminogen activator (rt-PA) remains the first-line treatment, its efficacy is limited by the low recanalisation rate in the setting of BAO.6 In patients with acute ischaemic stroke caused by a proximal intracranial occlusion of the anterior circulation, early mechanical thrombectomy (MT)
using stent retriever devices, as compared with intravenous rt-PA alone, improved functional outcome.7–9 However, in acute BAO patients with stroke, MT benefit has not yet been proven, although it seems to be a promising adjuvant or stand-alone therapy.10–24 Pending the results of future randomised controlled trials,25 the benefit and safety of stent retrievers MT remain to be determined in patients with stroke with acute BAO. We therefore analysed data from our clinical consecutive series and conducted a systematic review and meta-analysis to assess efficacy and safety profiles of stent retriever thrombectomy in BAO patients with stroke.
METHODS Neurological hospital series All consecutive patients treated with a Solitaire device (Covidien/ev3, Dublin, Ireland) at the Lyon Neurological Hospital between 1 March 2010 and 1 March 2013 were retrospectively analysed. Patients received intravenous rt-PA according to current guidelines (0.9 mg/kg), and a systematic approach including MT was implemented for patients. In patients with a contraindication to rt-PA, a direct MT approach was considered. Patients were eligible for MT if they (1) had a clinical diagnosis of acute stroke in the posterior circulation; (2) were admitted within 24 h after onset of symptoms; (3) had a significant clinical deficit following physician evaluation (no National Institutes of Health Stroke Scale (NIHSS) limit); (4) underwent an MRI or CT before treatment (no pc-ASPECTS limit); (5) presented with acute basilar ischaemia and BAO in MR or CTangiography. Patients were excluded if they (1) were pregnant; (2) were aged 6 h after the estimated time of BAO. However, although the time from symptom onset to recanalisation is associated with good clinical outcome, recanalisation of BAO up to 48 h after onset was found to be beneficial as well in the absence of extensive baseline ischaemia.28 Although the mortality rate is not negligible, MT in patients with BAO did not impact negatively on clinical outcomes. We showed a pooled estimate of 30% (95% CI 25% to 36%; 15 studies) mortality without significant heterogeneity ( p=0.34). The frequency of recanalisation could partly explain the relatively low mortality of patients with BAO treated with stent retrievers. In fact, the majority of patients with no or minimal recanalisation died after intravenous rt-PA or endovascular approach.1 6 28–30 34 In addition, stent retrievers achieved faster recanalisation, whereas a time-dependent relationship was reported between time to recanalisation therapy and risk of death.38 Similar safety profiles between endovascular therapy after intravenous rt-PA and intravenous rt-PA alone in the management of patients with large intracranial artery occlusions was also recently reported in the IMS-3 trial.39 The rate of sICH in the BASICS registry was 6% after intravenous rt-PA and 14% after intra-arterial therapy,1 whereas it was observed in only 4% after stent retrievers. This higher frequency of sICH could also explain the higher fatal evolution as it was previously reported to be independently associated with death, especially after intravenous rt-PA (OR, 14.6; 95% CI 1.4 to 157).29 However, this frequency of sICH may predominantly be caused by full-dose anticoagulation started concomitantly. The limitations of this study are due to the fact that the articles included in the systematic review contained both prospective and retrospective studies with a limited number of patients; some included combined anterior and posterior circulation occlusion patients with stroke. A range of different protocols were used: for example, Baek et al12 included patients with a baseline NIHSS score that was ≥4, no bilateral diffuse pontine
Table 2 Pooled rates of recanalisation and clinical outcomes Outcomes Successful recanalisation (TICI ≥2b) 90-day favourable outcome (mRS ≤2) Mortality Symptomatic intracranial haemorrhage*
Number of Studies
Number of Patients
Pooled Rates (95% CI)
15
312
81% (73%–87%)
14
288
42% (36%–48%)
15 14
312 288
30% (25%–36%) 4% (2%–8%)
*Symptomatic intracranial haemorrhage was defined as any parenchymal haematoma, subarachnoid haemorrhage or intraventricular haemorrhage associated with worsening of the National Institutes of Health Stroke Scale score by ≥4 within 24 h. mRS, modified Rankin Scale; TICI score, Thrombolysis In Cerebral Infarction.
Patients successfully recanalised with stent retrievers do not systematically present a favourable functional outcome. This finding may probably be explained by differences in admission characteristics of the patients.33 34 In fact, severe neurological condition on admission, with reduced consciousness and already permanent brain tissue damage, may lessen the benefits of recanalisation and hamper prognosis. It was demonstrated that poor 1-month outcome after BAO can be reliably predicted by older age, absence of hyperlipidaemia, presence of prodromal minor stroke, higher NIHSS score and longer time to treatment.34 Two main criteria that seemed to impact directly on clinical outcomes were (1) baseline ischaemic imaging lesions; and (2) time to recanalisation. However, such data were rarely described in the series we analysed or some studies did not provide full details of some baseline characteristics likely to be important for outcome, for example, hyperlipidaemia, pc-ASPECTS ( posterior circulation Acute Stroke Prognosis Early CT score), NIHSS score or time to recanalisation. Although we recently reported substantial reversal of early ischaemic damage in posterior circulation after Solitaire thrombectomy,35 the pretreatment infarct size seems to be a potent prognostic factor after either intravenous rt-PA or an endovascular therapy.36 37 In the prospective series of 184 consecutive patients with BAO treated with intravenous rt-PA, successful recanalisation led to a functionally favourable 90-day outcome in 50% of patients with no extensive brain infarction ( pc-ASPECTS ≥8), compared with 5.9% of patients with extensive brain infarction ( pc-ASPECTS
JNNP Online First, published on May 18, 2015 as 10.1136/jnnp-2014-310250 Cerebrovascular disease
RESEARCH PAPER
Outcomes of stent retriever thrombectomy in basilar artery occlusion: an observational study and systematic review Benjamin Gory,1 Islam Eldesouky,1 Rotem Sivan-Hoffmann,1 Murielle Rabilloud,2 Elodie Ong,3 Roberto Riva,1 Dorin Nicolae Gherasim,1 Alexis Turjman,1 Norbert Nighoghossian,3 Francis Turjman1 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ jnnp-2014-310250). 1
Department of Interventional Neuroradiology, Hôpital Neurologique Pierre Wertheimer, Bron, France 2 Department of Biostatitics, UMR 5558, Hospices Civils de Lyon, Lyon, France 3 Department of Neurology, Stroke Unit, Hôpital Neurologique Pierre Wertheimer, Bron, France Correspondence to Dr Benjamin Gory, Department of Interventional Neuroradiology, Hôpital Neurologique Pierre Wertheimer, 59 Boulevard Pinel, Bron 69677, France; [email protected] Received 26 December 2014 Revised 13 March 2015 Accepted 8 April 2015
ABSTRACT Background Basilar artery occlusion (BAO) remains one of the most devastating subtypes of stroke with high mortality and poor outcome. Early recanalisation is the most powerful predictor of favourable outcome in patients with stroke, and may be improved with mechanical thrombectomy using stent retriever devices. However, the benefit in functional outcome and safety of stent retrievers are not yet well known. The aim of this study was to assess efficacy and safety profiles of stent retriever thrombectomy in BAO patients with stroke. Methods We analysed data retrospectively from our consecutive clinical series and conducted a systematic review and meta-analysis of all previous studies of stent retriever thrombectomy in BAO patients with stroke between November 2010 and April 2014. Results From March 2010 to March 2013, 22 patients with acute BAO were treated with a Solitaire stent retriever in our series. Favourable outcome was significantly associated with younger age and distal BAO. The literature search identified 15 previous studies involving a total of 312 subjects. In the meta-analysis, including our series data, the recanalisation rate (Thrombolysis In Cerebral Infarction (TICI) score ≥2b) reached 81% (95% CI 73% to 87%). The rate of symptomatic intracranial haemorrhage was 4% (95% CI 2% to 8%), favourable outcome (modified Rankin Scale (mRS) ≤2 at 3 months) was found in 42% (95% CI 36% to 48%) and mortality rate was 30% (95% CI 25% to 36%). Conclusions Stent retriever thrombectomy is a safe treatment modality for patients with stroke presenting with BAO. Although the stent retrievers showed a good recanalisation rate, there are currently no randomised clinical trials to assess its clinical efficacy in comparison with the reference treatment. INTRODUCTION
To cite: Gory B, Eldesouky I, SivanHoffmann R, et al. J Neurol Neurosurg Psychiatry Published Online First: [please include Day Month Year] doi:10.1136/jnnp2014-310250
Strokes secondary to acute basilar artery occlusion (BAO) are associated with high mortality and poor outcome.1 2 Early recanalisation has been demonstrated to be the major goal of acute ischaemic stroke therapy.3–5 Although intravenous recombinant tissue plasminogen activator (rt-PA) remains the first-line treatment, its efficacy is limited by the low recanalisation rate in the setting of BAO.6 In patients with acute ischaemic stroke caused by a proximal intracranial occlusion of the anterior circulation, early mechanical thrombectomy (MT)
using stent retriever devices, as compared with intravenous rt-PA alone, improved functional outcome.7–9 However, in acute BAO patients with stroke, MT benefit has not yet been proven, although it seems to be a promising adjuvant or stand-alone therapy.10–24 Pending the results of future randomised controlled trials,25 the benefit and safety of stent retrievers MT remain to be determined in patients with stroke with acute BAO. We therefore analysed data from our clinical consecutive series and conducted a systematic review and meta-analysis to assess efficacy and safety profiles of stent retriever thrombectomy in BAO patients with stroke.
METHODS Neurological hospital series All consecutive patients treated with a Solitaire device (Covidien/ev3, Dublin, Ireland) at the Lyon Neurological Hospital between 1 March 2010 and 1 March 2013 were retrospectively analysed. Patients received intravenous rt-PA according to current guidelines (0.9 mg/kg), and a systematic approach including MT was implemented for patients. In patients with a contraindication to rt-PA, a direct MT approach was considered. Patients were eligible for MT if they (1) had a clinical diagnosis of acute stroke in the posterior circulation; (2) were admitted within 24 h after onset of symptoms; (3) had a significant clinical deficit following physician evaluation (no National Institutes of Health Stroke Scale (NIHSS) limit); (4) underwent an MRI or CT before treatment (no pc-ASPECTS limit); (5) presented with acute basilar ischaemia and BAO in MR or CTangiography. Patients were excluded if they (1) were pregnant; (2) were aged 6 h after the estimated time of BAO. However, although the time from symptom onset to recanalisation is associated with good clinical outcome, recanalisation of BAO up to 48 h after onset was found to be beneficial as well in the absence of extensive baseline ischaemia.28 Although the mortality rate is not negligible, MT in patients with BAO did not impact negatively on clinical outcomes. We showed a pooled estimate of 30% (95% CI 25% to 36%; 15 studies) mortality without significant heterogeneity ( p=0.34). The frequency of recanalisation could partly explain the relatively low mortality of patients with BAO treated with stent retrievers. In fact, the majority of patients with no or minimal recanalisation died after intravenous rt-PA or endovascular approach.1 6 28–30 34 In addition, stent retrievers achieved faster recanalisation, whereas a time-dependent relationship was reported between time to recanalisation therapy and risk of death.38 Similar safety profiles between endovascular therapy after intravenous rt-PA and intravenous rt-PA alone in the management of patients with large intracranial artery occlusions was also recently reported in the IMS-3 trial.39 The rate of sICH in the BASICS registry was 6% after intravenous rt-PA and 14% after intra-arterial therapy,1 whereas it was observed in only 4% after stent retrievers. This higher frequency of sICH could also explain the higher fatal evolution as it was previously reported to be independently associated with death, especially after intravenous rt-PA (OR, 14.6; 95% CI 1.4 to 157).29 However, this frequency of sICH may predominantly be caused by full-dose anticoagulation started concomitantly. The limitations of this study are due to the fact that the articles included in the systematic review contained both prospective and retrospective studies with a limited number of patients; some included combined anterior and posterior circulation occlusion patients with stroke. A range of different protocols were used: for example, Baek et al12 included patients with a baseline NIHSS score that was ≥4, no bilateral diffuse pontine
Table 2 Pooled rates of recanalisation and clinical outcomes Outcomes Successful recanalisation (TICI ≥2b) 90-day favourable outcome (mRS ≤2) Mortality Symptomatic intracranial haemorrhage*
Number of Studies
Number of Patients
Pooled Rates (95% CI)
15
312
81% (73%–87%)
14
288
42% (36%–48%)
15 14
312 288
30% (25%–36%) 4% (2%–8%)
*Symptomatic intracranial haemorrhage was defined as any parenchymal haematoma, subarachnoid haemorrhage or intraventricular haemorrhage associated with worsening of the National Institutes of Health Stroke Scale score by ≥4 within 24 h. mRS, modified Rankin Scale; TICI score, Thrombolysis In Cerebral Infarction.
Patients successfully recanalised with stent retrievers do not systematically present a favourable functional outcome. This finding may probably be explained by differences in admission characteristics of the patients.33 34 In fact, severe neurological condition on admission, with reduced consciousness and already permanent brain tissue damage, may lessen the benefits of recanalisation and hamper prognosis. It was demonstrated that poor 1-month outcome after BAO can be reliably predicted by older age, absence of hyperlipidaemia, presence of prodromal minor stroke, higher NIHSS score and longer time to treatment.34 Two main criteria that seemed to impact directly on clinical outcomes were (1) baseline ischaemic imaging lesions; and (2) time to recanalisation. However, such data were rarely described in the series we analysed or some studies did not provide full details of some baseline characteristics likely to be important for outcome, for example, hyperlipidaemia, pc-ASPECTS ( posterior circulation Acute Stroke Prognosis Early CT score), NIHSS score or time to recanalisation. Although we recently reported substantial reversal of early ischaemic damage in posterior circulation after Solitaire thrombectomy,35 the pretreatment infarct size seems to be a potent prognostic factor after either intravenous rt-PA or an endovascular therapy.36 37 In the prospective series of 184 consecutive patients with BAO treated with intravenous rt-PA, successful recanalisation led to a functionally favourable 90-day outcome in 50% of patients with no extensive brain infarction ( pc-ASPECTS ≥8), compared with 5.9% of patients with extensive brain infarction ( pc-ASPECTS
