Stent Retriever Therapy of Benefit to Stroke Patients

A multicenter trial the results of which were published in Radiology by Goyal et al indicated that if a patient with acute ischemic stroke is treated within two and half hours of ictus, 91% recover with little or no disability.  However after five and a half hours, favorable outcome goes down to 41%.

Data from 196 patients enrolled in the SWIFT PRIME trial, a global, multicenter, prospective study in which outcomes of patients treated with intravenous tissue plasminogen activator tPA alone or in combination with a thrombectomy device (Solitaire by Covidien, Irvine, CA) were analyzed.

In the stent retriever arm of the study, symptom onset to reperfusion time of 150 minutes or less led to 91% estimated probability of functional independence, which decreased by 10% over the next hour and by 20% with every subsequent hour of delay. Time from arrival at the emergency department to arterial access was 90 minutes (interquartile range, 69–120 minutes), and time to reperfusion was 129 minutes (interquartile range, 108–169 minutes). Patients who initially arrived at a referring facility had longer symptom onset to groin puncture times compared with patients who presented directly to an endovascular-capable center (275 versus 179.5 minutes, P < .001).

The findings of the trial strongly suggest that fast reperfusion leads to improved functional outcome among patients with acute stroke treated with stent retrievers and tPA.

The ENDOSTROKE Study

Singer et al in a study that was conducted at six centers and published in Radiology assessed the significance and role of collateral circulation in160 patients with proximal middle cerebral artery (MCA) occlusion; The ENDOSTROKE study.

Collateral vessel status was assessed at angiography by using the American Society of Interventional and Therapeutic Neuroradiology (ASITN) Society of Interventional Radiology (SIR) collateral vessel grading system, while using the Thrombolysis in Cerebral Infarction (TICI) scale assessed reperfusion. Good outcome was defined as a modified Rankin Scale score of 0–2 at follow-up.

Good clinical outcome was attained in 62 (39%) of the 160 patients, and TICI 2b–3 reperfusion was achieved in 94 (59%) patients. Nineteen patients had ASITN/SIR collateral vessel grades of 0 or 1, 63 patients had a grade of 2, and 78 patients had grades of 3 or 4.

Better collateral vessels were associated with higher reperfusion rates (21%, 48%, and 77% for ASITN/SIR grades of 0 or 1, 2, and 3 or 4, respectively; P < .001), a higher proportion of infarcts smaller than one-third of the MCA territory (32%, 48%, and 69% for ASITN/SIR grades of 0 or 1, 2, and 3 or 4, respectively; P < .001), and a higher proportion of good clinical outcome (11%, 35%, and 49% for ASITN/SIR grades of 0 or 1, 2, and 3 or 4, respectively; P = .007). At multivariable analysis, collateral vessel status independently predicted reperfusion, final infarct size, and clinical outcome. Within an onset-to-treatment time (OTT) of 0–3 hours, collateral vessel status predicted final infarct size and reperfusion. Within an OTT of 3–6 hours, it additionally predicted clinical outcome, with 53% of patients with ASITN/SIR grades of 3 or 4 having a good outcome, as compared with 0% of patients with grades of 0 or 1 and 27% of patients with a grade of 2 (P = .008).

The researchers concluded that collateral circulation independently predicted parameters such as reperfusion, infarct size, and clinical outcome.

Risk of Stroke due to Intracranial Atherosclerosis

Bos et al report in JAMA Neurology on the relationship between intracranial carotid artery calcifications and the risk of stroke in white populations.  As 80% to 90% of all strokes are due to acute ischemic strokes (AIS), it is important to recognize that atherosclerosis varies across the vascular beds and as such, different locations of vascular disease may have important role in AIS pathogenesis.  Atrial fibrillation and large-artery atherosclerosis such as in aortic arch and extra-cranial carotids are recognized as a major risk factors for AIS.  How common strokes occur after occlusion of the small intra-cerebral arteries, in so-called cerebral small-vessel disease is not well understood.

Between the years 2003 and 2006, a random sample of 2323 stroke-free persons (mean age, 69.5 years) underwent computed tomography scanning to quantify intracranial carotid artery calcification burden.  The population-based cohort was from the general community and part of the Rotterdam Study. All participants were continuously monitored for the occurrence of stroke until January 1, 2012.

During 14 055 person-years of follow-up, 91 participants had a stroke, of which 74 were acute ischemic strokes.  Large intracranial carotid artery calcification burden was related to a higher risk of stroke, independent of cardiovascular risk factors, ultrasound carotid plaque score, and calcification in other vessels.  Intracranial carotid artery calcification contributed to 75% of all strokes; for aortic arch and extra-cranial carotid artery calcification this incidence was only 45% and 25%, respectively.  As the sum of risk factors for strokes exceeds 100%, it suggests interaction between them as well as that unknown causes may contribute to AIS.

The findings of their study establish intracranial atherosclerosis as a major risk factor for stroke in the general white population and suggest that its contribution to the number of all acute ischemic strokes may be greater than atherosclerosis in common and internal carotid arteries as well as that from the arch of the aorta.

Efficiencies Result in Better Outcomes in Patients with Strokes

Despite two decades of efforts to initiate therapy of patients with acute ischemic strokes (AIS) quickly, less than one-third of patients presenting with AIS in the United States, were treated within the guideline-recommended door-to-needle (DTN) time with tissue plasminogen activator (tPA).  Fonarow et al¹ article in JAMA discusses strategies that were implemented in a consortium of hospitals in order to reduce DTN time to 60 minutes or less for the initiation of thrombolysis with tPA in patients with acute ischemic strokes.

The Stroke initiative made recommendations to 1030 participating hospitals that treated 71 169 patients with AIS with tPA (27 319 during the pre-intervention period and 43 850 during the post-intervention period).  The quality stroke initiative included pre-notification of hospitals by emergency medical services (EMS), fast performance and interpretation of brain CT scans, immediate initiation of treatment for eligible patients, rapid feedback on performance and public recognition of high-performing hospitals.

Median DTN time for tPA administration declined from 77 minutes during the pre-intervention period to 67 minutes during the post-intervention period (P < .001). The DTN times for tPA administration of 60 minutes or less increased from 26.5% of patients during the pre-intervention period to 41.3% during the post-intervention period (P < .001). The annual rate of improvement in DTN times of 60 minutes or less increased from 1.36% per year pre-intervention to 6.20% per year post-intervention (P < .001). In-hospital all-cause mortality improved significantly from the pre-intervention to the post-intervention period from 9.93% to 8.25%, respectively (P < .001), symptomatic intracranial hemorrhage within 36 hours decreased from 5.68% to 4.68% (P < .001), and discharge to home was more frequent from 37.6% to 42.7% (P < .001).

Prior studies² have established that thrombolysis with tPA is effective when administered early with the goal being to initiate treatment within 60 minutes or less from the time patients arrive in the hospital.  The authors report that their initiative was associated with improved timeliness of thrombolysis following acute ischemic stroke on a national scale, and that this improvement was associated with lower in-hospital mortality and intracranial hemorrhage, along with an increase in the percentage of patients discharged home.

1.  Fonarow G, Zhao X, Smith E, Saver J et al. Door-to-Needle Times for Tissue Plasminogen Activator Administration and Clinical Outcomes in Acute Ischemic Stroke Before and After a Quality Improvement Initiative; JAMA. 2014;311(16):1632-1640.    doi:10.1001/jama.2014.3203.

2.  Hacke W, Donnan G, Fieschi C, Kaste M et al, Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 2004 Mar 6; 363(9411): 768-74.