By Matthew E. Fink, MD, Editor
Feil Professor and Chairman, Department of Neurology, and Assistant Dean of Clinical Affairs, Weill Cornell Medical College; Neurologist-in-Chief, New York Presbyterian Hospital
Dr. Fink reports no financial relationships relevant to this field of study.
Message from the editor: The following reviews of studies presented at the 2020 International Stroke Conference were written after my personal attendance at the presentations, followed by review of the simultaneous publications in Stroke. All comments and opinions are solely those of this editor.
Safety and Efficacy of Endovascular Treatment for Basilar Artery Occlusion
SOURCE: Writing Group for the BASILAR Group, Zi W, Qiu Z, et al. Assessment of endovascular treatment for acute basilar artery occlusion via a nationwide prospective registry. JAMA Neurol 2020; Feb. 20. doi:10.1001/jamaneurol.2020.0156. [Epub ahead of print].
The efficacy of endovascular treatment for acute ischemic stroke in the anterior circulation has been well established but is uncertain in patients with acute basilar artery occlusion. This study was a nationwide prospective registry of patients presenting with an acute basilar artery occlusion at 47 comprehensive stroke centers across 15 provinces in China. Patients who presented within 24 hours of estimated stroke onset were divided into two groups: standard medical treatment alone or standard medical treatment plus endovascular therapy. The primary outcome measure was improvement in the modified Rankin scale (mRS) score at 90 days and adjusted for pre-specified prognostic factors. Safety outcomes included symptomatic intracerebral hemorrhage and 90-day mortality.
Over a five-year period, 829 patients were recruited into the study, with 647 treated with endovascular therapy in addition to standard medical therapy, and 182 treated with standard medical therapy alone. Ninety-day functional outcomes were better with endovascular therapy (odds ratio [OR] = 3.07, P < 0.001). In addition, endovascular therapy was associated with a higher rate of improvement with an mRS ≤ 3 at 90 days (OR = 4.70, P < 0.001). Patients treated with endovascular therapy also had a lower rate of 90-day mortality, although they did have an increased rate of symptomatic intracerebral hemorrhage (7.1% vs. 0.5%, P < 0.001).
In this prospective observational registry, endovascular therapy demonstrated improved functional outcome and reduced mortality.
BP Management After Mechanical Thrombectomy for Ischemic Stroke
SOURCE: Petersen NH, Silverman A, Strander SM, et al. Fixed compared with autoregulation-oriented blood pressure thresholds after mechanical thrombectomy for ischemic stroke. Stroke 2020;51:914-921.
Endovascular thrombectomy is now a standard treatment for patients who present with acute ischemic stroke from large vessel occlusions. The optimal management of blood pressure following thrombectomy is controversial, with current guidelines recommending maintenance of blood pressure < 180/105 mmHg for at least 24 hours after the procedure. However, there have been no randomized trials to determine the optimal blood pressure. The feared post-procedure complications are hemorrhage and malignant cerebral edema, because of disruption of cerebral autoregulation. This novel study used near-infrared spectroscopy correlated with continuous blood pressure measurement to develop an autoregulation algorithm that could be determined for each individual patient. By using this algorithm, investigators could identify the optimal blood pressure range where autoregulation was intact. The details of the technique should be reviewed by interested readers in the full paper.
The investigators enrolled 90 patients who were undergoing endovascular thrombectomy. Autoregulatory function was determined using near-infrared spectroscopy-derived tissue oxygenation in response to changes in arterial blood pressure. For each patient, an ideal blood pressure range was determined. The mean age of patients was 71.6 years, with 47% female, and mean National Institutes of Health stroke scale = 13.9. Patients who had a percentage of time with the mean arterial pressure above the upper limit of autoregulation as determined by this method had a worse 90-day outcome, (odds ratio per 10% time = 1.84, P = 0.002), and this also was correlated with a higher rate of hemorrhagic transformation. This was an observational study without randomization or comparative groups, but the technique of determining autoregulation appears to be sound, and further study is warranted to evaluate this technique to improve the post-procedure treatment of patients undergoing endovascular thrombectomy.
Diabetes Education for Patients Hospitalized with Stroke
SOURCE: Stone S, Drobycki N, Johnson M. Abstract NS5: Use of a multidisciplinary approach to successfully improve inpatient diabetes self-management education and diabetes medication reconciliation at discharge for persons with diabetes and stroke at a major academic medical center. Stroke 2020;51:ANS5.
A team of nurses at UT Southwestern Medical Center in Dallas undertook a project to improve diabetes education for stroke patients. At their center, they noted that 40% of stroke patients have diabetes, yet only 11% received diabetes education and only 59% had diabetes medication prescribed at the time of discharge from the hospital. The team initiated an educational program to improve these parameters. The endocrinology team was consulted for all stroke patients with a history of diabetes or those who had an A1c level of 7% or more. They worked with the neurology team and provided diabetes education for the patient and advised the neurology team on the appropriate discharge medication regimen and follow-up. Stroke coordinators provided reminders to the teams and to the patients to order consultations for patients who had hemoglobin A1c 7% or greater. Comparing 2017 to 2019, inpatient diabetes education improved from 11% to 96%, and discharge medications improved from 59% in 2017 to 93% in 2019. These metrics reflect improvement in care as the result of an inpatient educational program.
Disability After Minor Stroke and TIA — Secondary Analysis of the POINT Trial
SOURCE: Cucchiara B, Elm J, Easton JD, et al. Disability after minor stroke and transient ischemic attack in the POINT trial. Stroke 2020;51:792-799.
Early treatment of minor stroke and transient ischemic attacks (TIAs) with antiplatelet medication reduces the risk and severity of recurrent stroke. The POINT trial demonstrated that dual antiplatelet treatment with aspirin and clopidogrel resulted in a lower rate of recurrent stroke than with aspirin alone. The investigators then did a secondary analysis to determine if disability at 90 days was different between the two groups as well.
At 90 days, 9.6% of patients enrolled with TIA and 18.2% of patients enrolled with minor stroke were disabled. Overall disability was similar between the groups whether assigned to dual antiplatelet therapy or aspirin alone (14.7% vs. 14.3%). However, there were fewer patients with disability in conjunction with the primary outcome event in the dual antiplatelet treatment arm, but this did not reach statistical significance. The investigators also analyzed the combination of the index event with recurrent stroke and thought that there was a decrease in disability in the dual antiplatelet treatment arm. A multivariate analysis was performed and indicated that risk factors for disability following TIA included age, subsequent stroke, serious adverse events, and major bleeding. Although the data from this analysis suggest that disability might be less with dual antiplatelet therapy, differences between the groups were small, did not show robust findings, and did not reach statistical significance in most of the analyses.
Survival After Ischemic Stroke Has Improved During the Past 25 Years
SOURCE: Waziry R, Heshmatollah A, Bos D, et al. Time trends in survival following first hemorrhagic or ischemic stroke between 1991 and 2015 in the Rotterdam study. Stroke 2020;51:STROKEAHA119027198.
The Rotterdam study is a prospective community-based cohort study that started in 1990 and followed residents aged 55 years and older. They participated in baseline examinations and follow-up regarding cerebrovascular events. The investigators analyzed their follow-up data to determine if there was a temporal trend in survival, changes in age-standardized death rates, or changes in survival probabilities from the 1990s until 2015.
In evaluating the hemorrhagic stroke group, investigators found that 144 deaths occurred during 386 person-years. The investigators observed a similar mortality rate over the years, with 30 per 100 person-years in 2015 compared to 25 per 100 person-years in 1991. Similarly, mortality rates remained unchanged for hemorrhagic stroke between the years 1991 and 2015. However, in the ischemic stroke group, they observed a decline in mortality rates in 2015 of 11 per 100 person-years compared with the 1991 rates of 29 per 100 person-years. This translates to a favorable trend in the latest time period, with a hazard ratio of 0.71, P < 0.01. The investigators concluded that survival following ischemic stroke has improved over the past several decades, while no change has been observed in survival following hemorrhagic stroke.
Trends in Stroke Incidence Over Time
SOURCE: Madsen TE, Khoury JC, Leppert M, et al. Temporal trends in stroke incidence over time by sex and age in the GCNKSS. Stroke 2020;51:1070-1076.
The greater Cincinnati/Northern Kentucky Stroke Study is a prospective survey of all strokes among residents ≥ 20 years of age in all local hospitals for a population of 1.3 million people. The data were collected during five periods — July 1993 to June 1994, and calendar years 1999, 2005, 2010, and 2015. Sex-specific incidence rates were calculated and adjusted for age and race. Sex-specific case fatality rates also were reported. Over the five study periods, there were 9,733 strokes, and 56.3% were in women. In the period 1993/1994, women had 229 incident strokes per 100,000 population, and in 2015, they had 174 strokes per 100,000 population. For men, there were 282 strokes in 1993/1994, and 211 in 2015. Rates decreased between the first and last study periods for both sexes for ischemic stroke, but the rates for intracerebral hemorrhage and subarachnoid hemorrhage did not decline over the years. The investigators also noted that stroke incidence increased for men in the 22- to 44-year-old age group. Future studies should investigate the reasons for increasing stroke rates in the younger age groups, and why there has been no improvement in the incidence and survival in patients with hemorrhagic stroke.
Mobile Stroke Unit in Australia Speeds Up Time to Thrombectomy
SOURCE: Zhao H, Coote S, Easton D, et al. Melbourne mobile stroke unit and reperfusion therapy: Greater clinical impact of thrombectomy than thrombolysis. Stroke 2020;51:922-930.
Mobile stroke units (MSUs) are specially designed ambulances that have an integral computed tomography scanner, connect to a stroke neurologist via telemedicine, and carry thrombolytic drugs that can be administered in the field. Many reports have demonstrated that these units can treat patients with intravenous thrombolysis significantly faster than traditional ambulance transportation to a hospital emergency room. A recently deployed unit in Melbourne, Australia, reported its experience in the first year with intravenous thrombolysis, as well as the effect of the unit on time to endovascular thrombectomy.
In the first year of operation, prehospital thrombolysis was administered to 100 patients (mean age 73.8 years, 62% were male). The median time savings per MSU patient compared to controls, measuring time from dispatch to hospital arrival, was 26 minutes, and 15 minutes faster from hospital arrival to thrombolysis. The calculated overall time savings from time of dispatch to thrombolysis was 42.5 minutes. During the same period of time, 41 MSU patients were treated with endovascular thrombectomy, with a median dispatch-to-treatment time savings of 51 minutes (P < 0.001). This included a median time savings of 17 minutes from arrival at the hospital to arterial puncture. Using a calculation for disability-adjusted life-years, MSU evaluation and treatment resulted in reduced disability life-years of 20.9 for intravenous trauma lysis and 24.6 for endovascular thrombectomy. The investigators emphasized that the benefits of prehospital evaluation and triage for endovascular centers is facilitated workflow and reduced time to endovascular thrombectomy.
Mobile Stroke Units Result in Improved Functional Outcome After Ischemic Stroke
SOURCE: Ebinger M, Siegerink B, Kunz A, et al. LB5 - Effects of pre-hospital acute stroke treatment as measured with the modified Rankin scale; the Berlin - Pre-Hospital Or Usual Care Delivery trial (B_PROUD). Presented at the International Stroke Conference, Feb. 20, 2020.
Mobile stroke units (MSUs) have been deployed in multiple cities in Europe, North America, Australia, and Asia, and all have demonstrated reduction in time to the administration of intravenous thrombolysis compared to conventional ambulance transport. The MSU team in Berlin, Germany, has been operating for several years, and presented their data regarding functional outcomes. This was a prospective observational trial with blinded outcome assessment, comparing functional outcomes of patients with acute ischemic stroke, 18 years of age or older, who requested medical dispatch during the hours of MSU operation. For inclusion, stroke codes were called within four hours of the onset of symptoms, and patients were excluded if symptoms resolved before the ambulance arrived. If there were absolute contraindications for either thrombolysis or thrombectomy, patients were excluded. The primary outcome was functional disability as measured by the three-month modified Rankin Scale scores, with disability ranging from 0 (no neurological deficits) to 6 (death) at three months. The coprimary outcomes were other functional categories: 1) able to ambulate, 2) able to live at home, 3) living with severe disability, or 4) living in an institutional setting.
Between Feb. 1, 2017, and May 8, 2019, there were 1,543 patients evaluated, and the primary outcomes were assessed in 1,506. Availability of the MSU for treatment reduced the odds ratio significantly for disability and death at three months (0.74, P = 0.003) but not in the coprimary outcome of functional categories (0.75, P < 0.057). Patients treated on the MSU had a higher rate of thrombolysis (60% vs. 48%), and alarm-to-treatment times were faster (50 minutes, P = 0.001). In concluding, the investigators stated that MSU availability improved functional outcome in patients with acute ischemic stroke, if they were eligible for thrombolysis and/or thrombectomy.
Sex Hormone-Binding Globulin and Stroke Risk in Women
SOURCE: Madsen TE, Luo X, Huang M, et al. Circulating SHBG (sex hormone-binding globulin) and risk of ischemic stroke. Findings from the WHI. Stroke 2020;51:1257-1264.
The role of endogenous sex steroids such as estradiol in postmenopausal women is controversial, and studies have conflicting results regarding their impact on cardiovascular diseases. Nevertheless, premenopausal women have a lower risk of ischemic stroke compared to men, and this finding disappears in postmenopausal women. Sex hormone-binding globulin (SHBG) is thought to play a role and has been shown to be inversely related to obesity, diabetes mellitus, and other cardiovascular disorders. SHBG is a protein that binds to and regulates testosterone and estradiol. It is thought to play a role in vascular risk factors, including insulin resistance, inflammation, diabetes mellitus, metabolic syndrome, and coronary heart disease. The Women’s Health Initiative (WHI) looked at the relationship of this globulin to ischemic stroke in an observational cohort of 161,808 postmenopausal women enrolled in the WHI from 1993 to 1998.
Investigators identified 13,192 participants free of stroke at baseline. These participants were included in the follow-up studies and had levels of serum SHBG measured. They were stratified into quintiles, and had risk adjustments for body mass index, hypertension, alcohol use, smoking, physical activity, reproductive risk factors, and diabetes. After an average follow-up of 11.6 years, 768 ischemic stroke events were identified. Compared to the highest quintile of measured SHBG, women in the lowest quintile had an increased risk of ischemic stroke with a hazard ratio of 1.88 (P < 0.05). Risk adjustment did not eliminate the inverse associations between SHBG and ischemic stroke. Measurements of estradiol and testosterone and adjustment of SHBG levels for hormone levels did not eliminate the inverse relationship between SHBG and ischemic stroke, suggesting that this globulin may play an independent role as a stroke risk factor.
Benefits of Targeting LDL Cholesterol Below 70 mg/dL
SOURCE: Amarenco P, Kim JS, Labreuche J, et al. Benefit of targeting LDL (low-density lipoprotein) cholesterol <70 mg/dL during 5 years after ischemic stroke. Stroke 2020;51:1231-1239.
In the SPARCL trial (N Engl J Med 2006;355:549-559), treatment of patients with atorvastatin 80 mg per day resulted in a 16% relative risk reduction in stroke during 4.9 years of follow-up, compared to placebo. In a subgroup with carotid artery stenosis, the relative risk reduction was 33%. Patients who had a low-density lipoprotein (LDL) cholesterol less than 70 mg/dL had a 28% relative risk reduction compared to patients who only achieved an LDL cholesterol of 100 mg/dL or above. Amarenco et al specifically focused on targeting an LDL cholesterol below 70 mg/dL in patients who had ischemic stroke or transient ischemic attack (TIA) with evidence of atherosclerosis. The patients were stratified into two groups, where statins were titrated to reach an LDL cholesterol of less than 70 mg/dL or with an LDL of 100 mg/dL. Investigators were free to use any statin of their choice, and this could be combined with ezetimibe or other medications as needed. This was an open-label trial, and patients and investigators were not blinded to treatments. The primary endpoint was the composite of nonfatal stroke, nonfatal myocardial infarction, unstable angina, TIA, and vascular death. Patients were enrolled from 2010 until 2018. The study was ended early, after 277 primary endpoints were accrued, because of lack of funds. Median follow-up was 3.5 years.
The groups achieved mean LDL cholesterol of 66 mg/dL and 96 mg/dL, respectively. The primary endpoint occurred in 9.6% and 12.9% of patients, respectively, with a hazard ratio in favor of lower cholesterol of 0.74, P = 0.019. Ischemic stroke or urgent carotid revascularization following TIA was reduced by 27%. The primary outcome was reduced by 25%. There was no significant difference in the numbers of intracranial hemorrhages that occurred between the two groups. The investigators concluded that after an ischemic stroke of atherosclerotic origin, targeting LDL cholesterol to less than 70 mg/dL resulted in a significant reduction in subsequent major vascular events and no increase in intracranial hemorrhage.