Haitham M. Hussein

Effect of Systolic Blood Pressure Reduction on Hematoma Expansion, Perihematomal Edema, and 3-Month Outcome Among Patients With Intracerebral Hemorrhage: Results From the Antihypertensive Treatment of Acute Cerebral Hemorrhage Study

BACKGROUND Evidence indicates that systolic blood pressure (SBP) reduction may reduce hematoma expansion in patients with intracerebral hemorrhage (ICH) who are initially seen with acute hypertensive response. OBJECTIVE To explore the relationship between different variables of SBP reduction and hematoma expansion, perihematomal edema, and 3-month outcome among patients with ICH. DESIGN Post hoc analysis of a traditional phase 1 dose-escalation multicenter prospective study. SETTING Emergency departments and intensive care units. PATIENTS Patients having ICH with an elevated SBP of at least 170 mm Hg who were seen within 6 hours of symptom onset. INTERVENTION Systolic blood pressure reduction using intravenous nicardipine hydrochloride targeting 3 tiers of sequentially escalating SBP reduction goals (170-199, 140-169, or 110-139 mm Hg). MAIN OUTCOME MEASURES We evaluated the effect of SBP reduction (relative to initial SBP) on the following: hematoma expansion (defined as an increased intraparenchymal hemorrhage volume >33% on 24-hour vs baseline computed tomographic [CT] images), higher perihematomal edema ratio (defined as a >40% increased ratio of edema volume to hematoma volume on 24-hour vs baseline CT images), and poor 3-month outcome (defined as a modified Rankin scale score of 4-6). RESULTS Sixty patients (mean [SD] age, 62.0 [15.1] years; 34 men) were recruited (18, 20, and 22 patients in each of the 3 SBP reduction goal tiers). The median area under the curve (AUC) (calculated as the area between the hourly SBP measurements over 24 hours and the baseline SBP) was 1360 (minimum, 3643; maximum, 45) U. Comparing patients having less vs more aggressive SBP reduction based on 24-hour AUC analysis, frequencies were 32% vs 17% for hematoma expansion, 61% vs 40% for higher perihematomal edema ratio, and 46% vs 38% for poor 3-month outcome (P > .05 for all). The median SBP reductions were 54 mm Hg at 6 hours and 62 mm Hg at 6 hours from treatment initiation. Comparing patients having equal to or less vs more than the median SBP reduction at 2 hours, frequencies were 21% vs 31% for hematoma expansion, 42% vs 57% for higher perihematomal edema ratio, and 35% vs 48% for poor 3-month outcome (P > .05 for all). CONCLUSIONS We found no significant relationship between SBP reduction and any of the outcomes measured herein; however, the Antihypertensive Treatment of Acute Cerebral Hemorrhage study was primarily a safety study and was not powered for such end points. The consistent favorable direction of these associations supports further studies with an adequately powered randomized controlled design to evaluate the efficacy of aggressive pharmacologic SBP reduction.

Occurrence and Predictors of Futile Recanalization following Endovascular Treatment among Patients with Acute Ischemic Stroke: A Multicenter Study

BACKGROUND AND PURPOSE: Although recanalization is the goal of thrombolysis, it is well recognized that it fails to improve outcome of acute stroke in a subset of patients. Our aim was to assess the rate of and factors associated with “futile recanalization,” defined by absence of clinical benefit from recanalization, following endovascular treatment of acute ischemic stroke. MATERIALS AND METHODS: Data from 6 studies of acute ischemic stroke treated with mechanical and/or pharmacologic endovascular treatment were analyzed. “Futile recanalization” was defined by the occurrence of unfavorable outcome (mRS score of ≥3 at 1–3 months) despite complete angiographic recanalization (Qureshi grade 0 or TIMI grade 3). RESULTS: Complete recanalization was observed in 96 of 270 patients treated with IA thrombolysis. Futile recanalization was observed in 47 (49%). In univariate analysis, patients with futile recanalization were older (73 ± 11 versus 58 ± 15 years, P < .0001) and had higher median initial NIHSS scores (19 versus 14, P < .0001), more frequent BA occlusion (17% versus 4%, P = .049), less frequent MCA occlusion (53% versus 76%, P = .032), and a nonsignificantly higher rate of symptomatic hemorrhagic complications (2% versus 9%, P = .2). In logistic regression analysis, futile recanalization was positively associated with age >70 years (OR, 4.4; 95% CI, 1.9–10.5; P = .0008) and initial NIHSS score 10–19 (OR, 3.8; 95% CI, 1.7–8.4; P = .001), and initial NIHSS score ≥20 (OR, 64.4; 95% CI, 28.8–144; P < .0001). CONCLUSIONS: Futile recanalization is a relatively common occurrence following endovascular treatment, particularly among elderly patients and those with severe neurologic deficits.

Endovascular Interventions following Intravenous Thrombolysis May Improve Survival and Recovery in Patients with Acute Ischemic Stroke: A Case-Control Study

BACKGROUND AND PURPOSE: Since the introduction of recombinant tissue plasminogen activator (rtPA) into clinical practice in the mid 1990s, no adjunctive treatment has further improved clinical outcomes in patients with ischemic stroke. The safety, feasibility, and efficacy of combining intravenous (IV) rtPA with endovascular interventions has been described; however, no direct comparative study has yet established whether endovascular interventions after IV rtPA are superior to IV rtPA alone. A retrospective case-control study was designed to address this issue. MATERIALS AND METHODS: Between 2003 and 2006, 33 consecutive patients with acute ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) scores ≥10 were treated with IV rtPA in combination with endovascular interventions (IV plus intervention) at a tertiary care facility. Outcomes were compared with a control cohort of 30 consecutive patients treated with IV rtPA (IV only) at a comparable facility where endovascular interventions were not available. RESULTS: Baseline parameters were similar between the 2 groups. We found that the IV-plus-intervention group experienced significantly lower mortality at 90 days (12.1% versus 40.0%, P = .019) with a significantly greater improvement in NIHSS scores by the time of discharge or follow-up (P = .025). In the IV-plus-intervention group, patients with admission NIHSS scores between 10 and 15 and patients ≤80 years of age showed the greatest improvement, with a significant change of the NIHSS scores from admission (P = .00015 and P = .013, respectively). CONCLUSIONS: In this small case-control study of patients with acute ischemic stroke and admission NIHSS scores ≥10, there was a suggestion of incremental clinical benefit among patients receiving endovascular interventions following standard administration of IV rtPA.

CONCURRENT COMPARISON OF OUTCOMES OF PRIMARY ANGIOPLASTY AND OF STENT PLACEMENT IN HIGH-RISK PATIENTS WITH SYMPTOMATIC INTRACRANIAL STENOSIS

OBJECTIVE To compare the long-term outcomes of treatment of symptomatic intracranial stenosis using primary angioplasty or stent placement. Both primary angioplasty and stent placement have been proposed as treatment modalities, but long-term outcome comparisons are not available. METHODS We determined rates of technical success and rates of major stroke, second procedure, or death in patients with symptomatic intracranial stenosis (>or=70% in severity and/or medication failure). Pre- and posttreatment angiographic stenosis was measured by independent reviewers. Angioplasty was used preferentially in patients with more technically challenging lesions. Kaplan-Meier analysis was used to determine the rate of major stroke-free survival and major stroke- or repeat procedure-free survival between the two treatment modalities over periods of 12 and 24 months. Cox proportional hazards analysis was used to determine the differential risk of major stroke or death after either angioplasty or stent placement. RESULTS Twenty-two patients (mean age, 62 +/- 13 yr) were treated with primary angioplasty and 22 patients (mean age, 58 +/-14 yr) with stent placement. The mean stenosis (+/-standard deviation) decreased from 76 +/- 13% to 28 +/- 18% in the primary angioplasty-treated and from 68 +/- 9% to 17 +/- 13% in the stent-treated group. There was no difference in time to major stroke or death (log-rank statistic, 0.44; P = 0.5), and time to major stroke, repeat procedure, or death (log-rank statistic, 0.78; P = 0.4) between the two treatment groups. At 12 months, major stroke-free survival was 95% (+/- standard error of 4%) for the stent-treated patients and 93% (+/- standard error of 7%) for the angioplasty-treated patients. There was no significant difference in the risk of major stroke or death between angioplasty and stent placement (P = 0.996) using Cox proportional hazards analysis after adjusting for age, gender, race/ethnicity, presence of hyperlipidemia, qualifying event, preprocedure stenosis, and target vessel. CONCLUSION The results of primary angioplasty and primary stent placement were comparable at intermediate follow-up examination after the procedure. The results highlight the need for carefully designed, randomized clinical trials to determine the precise value of stent placement in the intracranial circulation.

A Multicenter Analysis of “Time to Microcatheter” for Endovascular Therapy in Acute Ischemic Stroke

At present, no time recommendation for initiation of endovascular treatment in acute ischemic stroke is available. A multicenter analysis was designed to identify variables that prolong “time to microcatheter,” defined as the time interval from computed tomographic scan to microcatheter placement in the cerebral circulation.

Reliability of Hematoma Volume Measurement at Local Sites in a Multicenter Acute Intracerebral Hemorrhage Clinical Trial

Background and Purpose— The reliability of hematoma volume (HV) measurement using the ABC/2 method in multicenter clinical trials is unknown. We determined the accuracy of ABC/2 method as an on-site test in comparison with the gold standard central HV-assessment and semiautomatic HV-assessment. Method— We analyzed data from an acute intracerebral hemorrhage multicenter clinical trial. HV was measured by site investigators to determine enrollment eligibility (<60 cm3) using the ABC/2 method (on-site HV), and independently by the core-imaging laboratory using computer-based analysis (Medical Image Processing, Analysis, and Visualization [MIPAV] HV). HV was also measured by ABC/2 method (central HV) at the core-imaging laboratory to assess the difference in measurements between on-site (multiple raters with variable experiences) and central (single experienced rater) HVs. Results— Fifty-six subjects were analyzed (mean age 62±15 years; 45% women). On-site HV values showed a significantly lower correlation with the MIPAV HV (r=0.63) than central HV and MIPAV HV (r=0.93) values. The correlation between on-site HV and central HV values was modest (r=0.51). A total of 73% of the central HVs were within 25% of the corresponding MIPAV HVs, whereas only 46% of the on-site HVs were within 25% of the corresponding MIPAV HVs (P<0.001). One protocol violation occurred as a result of inaccuracy of on-site HV measurement. Conclusion— On-site HV measurements showed high variability, but the impact on the eligibility determination was small. Centralized remeasurements of HVs with feedback to the sites may increase the reliability of the on-site HV measurements. Clinical Trial Registration— URL: http://www.clinicaltrials.gov/ct2/show/NCT00415610 or http://www.atach-2.com. Unique identifier: NCT00415610.

Postprocedure Intravenous Eptifibatide Following Intra-Arterial Reteplase in Patients with Acute Ischemic Stroke

Early use of intravenous platelet glycoprotein IIB/IIIA antagonists after intra‐arterial (IA) thrombolysis may reduce the risk of reocclusion and microvascular compromise.

Systolic Blood Pressure Reduction and Risk of Acute Renal Injury in Patients with Intracerebral Hemorrhage

BACKGROUND Aggressive systolic blood pressure reduction may precipitate acute renal injury because of underlying hypertensive nephropathy in patients with intracerebral hemorrhage. The studys objective was to determine the rate and determinants of acute renal injury during acute hospitalization among subjects with intracerebral hemorrhage using a post hoc analysis of a multicenter prospective study. METHODS Subjects with intracerebral hemorrhage and elevated systolic blood pressure of 170 mm Hg or greater who presented within 6 hours of symptom onset and underwent treatment of acute hypertensive response and fluid management as per study and local protocols, respectively. Acute renal injury was defined post hoc using the criteria used in Acute Kidney Injury Network classifications within 72 hours of admission. Descriptive statistics and standard statistical tests were used to characterize and evaluate the effect of systolic blood pressure reduction parameters (relative to initial systolic blood pressure) and average maximum hourly dose of nicardipine on the occurrence of acute renal injury. RESULTS A total of 60 subjects were recruited (57% were men; mean age of 62.0 ± 15.1 years). Five subjects (9%) had stage I acute renal injury according to the Acute Kidney Injury Network criteria. None of the subjects had stage II or III acute renal injury. The serum creatinine course for the first 3 days suggested that the peak elevation of creatinine was seen at 18, 30, 57, 58, and 71 hours after baseline measurements in these 5 subjects, all of which except for the first one were beyond the protocol-specified treatment period. The incidences of neurologic deterioration and symptomatic hematoma expansion were significantly greater in the subjects with stage I renal impairment. The systolic blood pressure reduction parameters (in particular, the area under the curve depicting the 24-hour systolic blood pressure summary statistic) and the higher average maximum hourly nicardipine dose were strongly associated with stage I renal impairment. CONCLUSIONS Although acute renal injury is infrequent and mild among subjects with intracerebral hemorrhage undergoing systolic blood pressure reduction, a trend in association between systolic blood pressure reduction and renal impairment was observed in this small study. Therefore, it is important to carefully monitor the renal function when administering treatment to reduce systolic blood pressure in patients with intracerebral hemorrhage.

A comparison of outcomes associated with carotid artery stent placement performed within and outside clinical trials in the United States

BACKGROUND A discrepancy between characteristics of patients treated with carotid angioplasty and stent placement (CAS) within and outside clinical trials, particularly characteristics with direct impact on clinical outcome, may limit generalization of clinical trial results. The objective of this study was to identify differences in demographic and clinical characteristics and outcomes related to CAS in patients treated within clinical trials and those treated outside clinical trials in a large national cohort. METHODS We determined the frequency of CAS performed within and outside clinical trials and associated in-hospital outcomes using data from the Nationwide Inpatient Survey data files from 2005 to 2009. All the in-hospital outcomes were analyzed after adjusting for potential confounders using multivariate analysis. RESULTS Of the 81,638 patients who underwent CAS, 16,078 (19.6%) underwent the procedure as part of a clinical trial. The mean age of the patients was significantly lower in patients treated with CAS as part of a clinical trial than those treated with CAS outside a clinical trial. The proportion of women and nonwhites was lower among patients treated with CAS as part of a clinical trial. The in-hospital mortality was two-fold higher among patients treated with CAS outside clinical trials (1.12% vs 0.53%; P = .0005). The rate of composite endpoint of stroke, cardiac events, and death was significantly higher among patients treated with CAS outside clinical trials (P = .02). After adjusting for age, gender, presence of renal failure, and hospital bed size, CAS performed as part of a clinical trial was associated with lower rates of in-hospital mortality (odds ratio, 0.467; 95% confidence interval, 0.290-0.751; P = .0017) and composite endpoint of stroke, cardiac events, and death (odds ratio, 0.752; 95% confidence interval, 0.594-0.952; P = .0180). CONCLUSIONS Our results suggest that CAS procedures performed as part of clinical trials was associated with lower rates of in-hospital mortality and composite endpoint of stroke, cardiac events, and death in United States. These findings highlight the need for strategies that ensure appropriate adoption of CAS to ensure that the benefits observed in clinical trials can be replicated in general practice.

Premorbid use of statins is associated with higher recanalization rates in patients with acute ischemic stroke undergoing endovascular treatment.

Statins have been shown to have lipid‐independent (pleiotropic) effects that may be beneficial in the management of vascular disease. We evaluated the effect of premorbid statin use on recanalization in patients with acute ischemic stroke undergoing endovascular treatment.