Sean P. Cullen

Statin Use During Ischemic Stroke Hospitalization Is Strongly Associated With Improved Poststroke Survival

Background and Purpose— Statins reduce infarct size in animal models of stroke and have been hypothesized to improve clinical outcomes after ischemic stroke. We examined the relationship between statin use before and during stroke hospitalization and poststroke survival. Methods— We analyzed records from 12 689 patients admitted with ischemic stroke to any of 17 hospitals in a large integrated healthcare delivery system between January 2000 and December 2007. We used multivariable survival analysis and grouped-treatment analysis, an instrumental variable method that uses treatment differences between facilities to avoid individual patient-level confounding. Results— Statin use before ischemic stroke hospitalization was associated with improved survival (hazard ratio, 0.85; 95% CI, 0.79–0.93; P<0.001), and use before and during hospitalization was associated with better rates of survival (hazard ratio, 0.59; 95% CI, 0.53–0.65; P<0.001). Patients taking a statin before their stroke who underwent statin withdrawal in the hospital had a substantially greater risk of death (hazard ratio, 2.5; 95% CI, 2.1–2.9; P<0.001). The benefit was greater for high-dose (>60 mg/day) statin use (hazard ratio, 0.43; 95% CI, 0.34–0.53; P<0.001) than for lower dose (<60 mg/day) statin use (hazard ratio, 0.60; 95% CI, 0.54–0.67; P<0.001; test for trend P<0.001), and earlier treatment in-hospital further improved survival. Grouped-treatment analysis showed that the association between statin use and survival cannot be explained by patient-level confounding. Conclusions— Statin use early in stroke hospitalization is strongly associated with improved poststroke survival, and statin withdrawal in the hospital, even for a brief period, is associated with worsened survival.

Long-term outcome of endovascular stenting for symptomatic basilar artery stenosis

Eighteen patients underwent stenting for symptomatic basilar artery stenosis. There were three major periprocedural complications (16.7%) without fatality. At a mean 26.7 ± 12.1-month follow-up, 15 patients (83.3%) had an excellent long-term outcome. Only one patient (5.6%) had moderate disability from recurrent stroke, and two patients died of medical illness at 30 and 36 months after stenting. In this uncontrolled study, stenting appeared to be effective in reducing stroke risk and death and worthy of further scrupulous trial.

Predicting Long-Term Outcome after Endovascular Stroke Treatment: The Totaled Health Risks in Vascular Events Score

BACKGROUND AND PURPOSE: Endovascular treatments are being increasingly used in acute ischemic stroke, and better tools are needed to determine which patients may benefit most from these techniques. We hypothesized that specific chronic diseases can be used, along with age and stroke severity, to predict endovascular stroke treatment outcomes. MATERIALS AND METHODS: Data from 2 single-arm trials of a thrombectomy device, MERCI and Multi MERCI, were pooled for analysis. A predictive score was developed by using the independent contribution of variables in multivariable analysis. RESULTS: HTN, DM, and AFib were found to predict outcomes. These 3 conditions contribute equally to a CDS that predicts outcomes independent of other predictor variables, including age, stroke severity, and vessel recanalization. A 10-level predictive score, the THRIVE score, which incorporates age, stroke severity, and the CDS, was developed. The THRIVE score strongly predicts outcome and mortality at 90 days. CONCLUSIONS: Specific chronic diseases influence poststroke outcomes among patients undergoing endovascular stroke treatment, independent of other predictors of outcome. The THRIVE score reflects the contributions of chronic disease, age, and stroke severity and strongly predicts endovascular stroke treatment outcomes.

Embolization of spinal cord arteriovenous shunts: morphological and clinical follow-up and results--review of 69 consecutive cases.

OBJECTIVEWe sought to analyze the results of embolization in patients with intradural spinal cord arteriovenous shunts. METHODSThe clinical and radiological files of 69 of a population of 155 patients treated with embolization between 1981 and 1999 were reviewed retrospectively. The patients’ clinical status was evaluated according to Karnofsky Performance Scale score. Twenty-one (14%) of 155 patients were treated surgically because they were thought to be poor candidates for embolization. Twenty-four (15%) of 155 patients were considered untreatable with surgery or embolization; in these patients, follow-up was proposed, but only 8 of them were followed appropriately and remained stable after the first consultation. Forty-one (26%) of 155 patients consulted our group, but no follow-up could be obtained. In 69 (45%) of 155 patients, comprising 20 children and 49 adults, endovascular treatment was performed with the patients under general anesthesia and without provocative tests, mainly with acrylic glue, in 99% of these patients. RESULTSThe mean number of diagnostic and therapeutic sessions was 3.5 per patient, and the mean number of pure therapeutic sessions was 1.5 per patient. Follow-up ranged between 6 months and 18 years (mean, 5.6 yr). In 16% of patients, anatomic obliteration of spinal cord arteriovenous shunts was obtained. Embolization reduced more than 50% of the spinal cord arteriovenous shunts in 86% of cases. No recanalization was noted on follow-up angiograms. Good clinical outcomes were obtained in 83% of the patients: 15% of them were asymptomatic, 43% were improved, and 25% were stable. In 4% of patients, embolization failed to stabilize the disease. Transient deficits were seen after embolization in 14% of the patients, and permanent severe complications occurred in 4% of the patients (Karnofsky Performance Scale score ≤70). Mild worsening was seen in 9% of the patients (Karnofsky Performance Scale score, 80). No bleeding or rebleeding was seen after endovascular treatment was considered to have been completed. CONCLUSIONThis study proves that embolization with acrylic glue is a therapeutic option that compares favorably with surgery or embolization with other agents (particles, coils, or balloons). It offers stable long-term clinical results, despite not necessarily achieving total cure. Studies of larger series with longer follow-up are necessary to confirm these encouraging therapeutic data.

Methods and Design Considerations for Randomized Clinical Trials Evaluating Surgical or Endovascular Treatments for Cerebrovascular Diseases

OBJECTIVEThe results of clinical trials affect the practice of surgery and endovascular therapy for cerebrovascular diseases. The purpose of this report is to review the basic components of the designs and methods for randomized clinical trials and to describe the influence of those components on the interpretation of trial results. METHODSThe goal of an optimal clinical trial of a new procedure is to provide the most objective and rigorous evaluation of the safety and effectiveness of that procedure. Anything in the design, performance, or analysis that impairs such an assessment decreases the ability of the trial to achieve its goal and answer the research question. To highlight the components of a clinical trial, this report uses examples of Phase III clinical trials that have influenced the practice of cerebrovascular surgery and endovascular therapy in the past three decades, including the International Cooperative Study of Extracranial/Intracranial Arterial Anastomosis, the North American Symptomatic Carotid Endarterectomy Trial, the Asymptomatic Carotid Atherosclerosis Study, the Prolyse in Acute Cerebral Thromboembolism II study, and the International Subarachnoid Aneurysm Trial. RESULTSThe research question (objective) of the trial must be clearly defined, with an objective measure of efficacy and a specified quantitative difference to define the superiority of one intervention over another, in a relatively homogeneous patient population. Allocation concealment, randomization with or without stratification, and blinding (or masking) are important strategies to prevent differences in the study populations that could adversely affect the conclusions of the study. The primary end point must correspond to the specific aims of the trial. It should be objectively defined, quantifiable, reliable, and reproducible. Commonly defined end points in surgical trials include changes from baseline illness or disease severity scores, morbidity and mortality rates, and relative risks of reaching an end point with time. The statistical methods used for interim and final analyses are important. The effects of dropouts, crossovers, and missing data should be understood in the context of the final analysis. Additional concepts, such as intention-to-treat analysis and use of actual versus predicted outcomes, are important with respect to interpretation of the final results of the study. CONCLUSIONThe neurosurgical and neuroendovascular communities are currently planning or conducting several clinical trials to evaluate new procedures for the treatment of cerebrovascular diseases. It is hoped that a better understanding of the components of clinical trials will facilitate the design and implementation of effective studies.

Inpatient statin use predicts improved ischemic stroke discharge disposition

Objective: To determine whether statin use is associated with improved discharge disposition after ischemic stroke. Methods: We used generalized ordinal logistic regression to analyze discharge disposition among 12,689 patients with ischemic stroke over a 7-year period at 17 hospitals in an integrated care delivery system. We also analyzed treatment patterns by hospital to control for the possibility of confounding at the individual patient level. Results: Statin users before and during stroke hospitalization were more likely to have a good discharge outcome (odds ratio [OR] for discharge to home = 1.38, 95% confidence interval [CI] 1.25–1.52, p < 0.001; OR for discharge to home or institution = 2.08, 95% CI 1.72–2.51, p < 0.001). Patients who underwent statin withdrawal were less likely to have a good discharge outcome (OR for discharge to home = 0.77, 95% CI 0.63–0.94, p = 0.012; OR for discharge to home or institution = 0.43, 95% CI 0.33–0.55, p < 0.001). In grouped-treatment analysis, an instrumental variable method using treatment patterns by hospital, higher probability of inpatient statin use predicted a higher likelihood of discharge to home (OR = 2.56, 95% CI 1.71–3.85, p < 0.001). In last prior treatment analysis, a novel instrumental variable method, patients with a higher probability of statin use were more likely to have a good discharge outcome (OR for each better level of ordinal discharge outcome = 1.19, 95% CI 1.09–1.30, p = 0.001). Conclusions: Statin use is strongly associated with improved discharge disposition after ischemic stroke.

THRIVE Score Predicts Ischemic Stroke Outcomes and Thrombolytic Hemorrhage Risk in VISTA

Background and Purpose— In previous studies, the Totaled Health Risks in Vascular Events (THRIVE) score has shown broad utility, allowing prediction of clinical outcome, death, and risk of hemorrhage after tissue-type plasminogen activator (tPA) treatment, irrespective of the type of acute stroke therapy applied to the patient. Methods— We used data from the Virtual International Stroke Trials Archive to further validate the THRIVE score in a large cohort of patients receiving tPA or no acute treatment, to confirm the relationship between THRIVE and hemorrhage after tPA, and to compare the THRIVE score with several other available outcome prediction scores. Results— The THRIVE score strongly predicts clinical outcome (odds ratio, 0.55 for good outcome [95% CI, 0.53–0.57]; P<0.001), mortality (odds ratio, 1.57 [95% confidence interval, 1.50–1.64]; P<0.001), and risk of intracerebral hemorrhage after tPA (odds ratio, 1.34 [95% confidence interval, 1.22–1.46]; P<0.001). The relationship between THRIVE score and outcome is not influenced by the independent relationship of tPA administration and outcome. In receiver operator characteristic curve analysis, the THRIVE score was superior to several other available outcome prediction scores in the prediction of clinical outcome and mortality. Conclusions— The THRIVE score is a simple-to-use tool to predict clinical outcome, mortality, and risk of hemorrhage after thrombolysis in patients with ischemic stroke. Despite its simplicity, the THRIVE score performs better than several other outcome prediction tools. A free Web calculator for the THRIVE score is available at http://www.thrivescore.org.

Assessment of vasculature of meningiomas and the effects of embolization with intra-arterial MR perfusion imaging : A feasibility study

BACKGROUND AND PURPOSE: Embolization of meningiomas has emerged as a preoperative adjuvant therapy that has proved effective in mitigating blood loss during surgical resection. Arterial supply to these tumors is typically identified by diffuse areas of parenchymal staining after selective x-ray angiograms. We investigate the benefits that selective injection of MR contrast may have in identifying vascular territories and determining the effects of embolization therapy. MATERIALS AND METHODS: Selective intra-arterial (IA) injection of dilute MR contrast media was used to assess the vascular distribution territories of meningeal tumors before and after embolization therapy. Regions of the tumor that experienced loss of signal intensity after localized contrast injections into the external and common carotid as well as vertebral arteries were used to quantify the specific vessels volume of distribution. Assessments were made before and after embolization to reveal changes in the vascular supply of the tumor. MR findings were compared with radiographic evaluation of tumor vascular supply on the basis of conventional x-ray angiography. RESULTS: MR proved to be an excellent means to assess tissue fed by selected arteries and clearly demonstrated the treated and untreated portions of the neoplasm after therapy. In some instances, MR revealed postembolization residual enhancement of the tumor that was difficult to appreciate on x-ray angiograms. Very low contrast dose was necessary, which made repeated assessment during therapy practical. CONCLUSION: MR perfusion imaging with selective IA injection of dilute contrast can reveal the distribution territory of vessels. Changes in tumor vasculature could be detected after embolization, which reveal the volumetric fraction of the tumor affected by the therapy.

Intraarterial Thrombolysis Trials in Acute Ischemic Stroke

Stroke is a common cause of death and disability in industrialized nations. Technical advances and the increased availability of noninvasive brain imaging techniques have permitted precise and early diagnosis of acute cerebral ischemia. This has made emergent thrombolytic therapy for rapid restoration of cerebral perfusion increasingly possible. Herein, the authors present a review of the clinical trials investigating acute stroke treatment with intraarterial thrombolysis.

Validation of the Totaled Health Risks In Vascular Events (THRIVE) score for outcome prediction in endovascular stroke treatment.

Background We recently developed the Totaled Health Risks In Vascular Events (THRIVE) score to predict outcomes after endovascular stroke treatment. The THRIVE score, which incorporates age, National Institutes of Health Stroke Scale score, and three medical comorbidities (hypertension, diabetes mellitus, and atrial fibrillation), was developed using data from the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials. Aims We set out to perform external validation of the THRIVE score using data from the largest registry of endovascular stroke treatment performed to date, the Merci Registry. Methods We compared the performance of the THRIVE score in two different data sets: the development cohort (the MERCI and Multi MERCI trials, n = 305) and a validation cohort (the Merci Registry, a prospective multicenter registry of patients undergoing endovascular stroke treatment, n = 1000). We examined the predictive utility of the THRIVE score across the range of clinical outcomes and used receiver–operator characteristics curve analysis to compare score performance in the two data sets. Results The THRIVE score predicted good outcome, death, and the full range of the modified Rankin Scale in a similar fashion between the MERCI trials and the Merci Registry. Receiver–operator characteristics curve comparisons showed no statistically significant difference in the performance of the THRIVE score between the two data sets: for good outcome, the receiver–operator characteristics area under the curve was 0.293 for the MERCI trials and 0.266 for the Merci Registry (P = 0.47) and for death, the receiver–operator characteristics area under the curve was 0.692 for the MERCI trials and 0.717 for the Merci Registry (P = 0.48). The THRIVE score and vessel recanalization were also found to be independent and unrelated predictors of clinical outcome. Conclusions The THRIVE score reliably predicts outcomes after endovascular stroke treatment and may be useful as a clinical prognostic tool and to perform severity adjustments in stroke clinical research.