Browsing by Author "Chen, Guofang"
Now showing 1 - 5 of 5
Results Per Page
Sort Options
Publication Associations of Early Systolic Blood Pressure Control and Outcome After Thrombolysis- Eligible Acute Ischemic Stroke: Results From the ENCHANTED Study(2022) Wang, Xia; Minhas, Jatinder S.; Moullaali, Tom J.; Di Tanna, Gian Luca; Lindley, Richard I.; Chen, Xiaoying; Arima, Hisatomi; Chen, Guofang; Delcourt, Candice; Bath, Philip M.; Broderick, Joseph P.; Demchuk, Andrew M.; Donnan, Geoffrey A.; Durham, Alice C.; Lavados, Pablo; Lee, Tsong-Hai; Levi, Christopher; Martins, Sheila O.; Olavarría, Verónica V.; Pandian, Jeyaraj D.; Parsons, Mark W.; Pontes-Neto, Octavio M.; Ricci, Stefano; Sato, Shoichiro; Sharma, Vijay K.; Silva, Federico; Thang, Nguyen H.; Wang, Ji-Guang; Woodward, Mark; Chalmers, John; Song, Lili; Anderson, Craig S.; Robinson, Thompson G.BACKGROUND AND PURPOSE: In thrombolysis-eligible patients with acute ischemic stroke, there is uncertainty over the most appropriate systolic blood pressure (SBP) lowering profile that provides an optimal balance of potential benefit (functional recovery) and harm (intracranial hemorrhage). We aimed to determine relationships of SBP parameters and outcomes in thrombolyzed acute ischemic stroke patients. METHODS: Post hoc analyzes of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial-factorial trial of thrombolysis-eligible and treated acute ischemic stroke patients with high SBP (150–180 mm Hg) assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) alteplase and intensive (target SBP, 130–140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) treatment. All patients were followed up for functional status and serious adverse events to 90 days. Logistic regression models were used to analyze 3 SBP summary measures postrandomization: attained (mean), variability (SD) in 1–24 hours, and magnitude of reduction in 1 hour. The primary outcome was a favorable shift on the modified Rankin Scale. The key safety outcome was any intracranial hemorrhage. RESULTS: Among 4511 included participants (mean age 67 years, 38% female, 65% Asian) lower attained SBP and smaller SBP variability were associated with favorable shift on the modified Rankin Scale (per 10 mm Hg increase: odds ratio, 0.76 [95% CI, 0.71–0.82]; P<0.001 and 0.86 [95% CI, 0.76–0.98]; P=0.025) respectively, but not for magnitude of SBP reduction (0.98, [0.93– 1.04]; P=0.564). Odds of intracranial hemorrhage was associated with higher attained SBP and greater SBP variability (1.18 [1.06–1.31]; P=0.002 and 1.34 [1.11–1.62]; P=0.002) but not with magnitude of SBP reduction (1.05 [0.98–1.14]; P=0.184). CONCLUSIONS: Attaining early and consistent low levels in SBP <140 mm Hg, even as low as 110 to 120 mm Hg, over 24 hours is associated with better outcomes in thrombolyzed acute ischemic stroke patients.Item Early Blood Pressure Lowering Does Not Reduce Growth of Intraventricular Hemorrhage following Acute Intracerebral Hemorrhage: Results of the INTERACT Studies(Karger, 2016) Chan, Edward; Anderson, Craig; Wang, Xia; Arima, Hisatomi; Saxena, Anubhav; Moullaali, Tom; Delcourt, Candice; Wu, Guojun; Wang, Jinchao; Chen, Guofang; Lavados, Pablo; Stampf, Christian; Robinson, Thompson; Chalmers, JohnBackground Intraventricular hemorrhage (IVH) extension is common following acute intracerebral hemorrhage (ICH) and is associated with poor prognosis. Aim To determine whether intensive blood pressure (BP)-lowering therapy reduces IVH growth. Methods Pooled analyses of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT1 and INTERACT2) computed tomography (CT) substudies; multicenter, open, controlled, randomized trials of patients with acute spontaneous ICH and elevated systolic BP, randomly assigned to intensive (<140 mm Hg) or guideline-based (<180 mm Hg) BP management. Participants had blinded central analyses of baseline and 24-hour CT. Association of BP lowering to IVH growth was assessed in analysis of covariance. Results There was no significant difference in adjusted mean IVH growth following intensive (n = 228) compared to guideline-recommended (n = 228) BP treatment (1.6 versus 2.2 ml, respectively; p = 0.56). Adjusted mean IVH growth was nonsignificantly greater in patients with a mean achieved systolic BP ≥160 mm Hg over 24 h (3.94 ml; p trend = 0.26). Conclusions Early intensive BP-lowering treatment had no clear effect on IVH in acute ICH.Item Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED): an international, randomised, open-label, blinded-endpoint, phase 3 trial(Elsevier Ltd., 2019-03) Anderson, Craig; Huang, Yining; Lindley, Richard; Chen, Xiaoying; Arima, Hisatomi; Chen, Guofang; Li, Qiang; Billot, Laurent; Delcourt, Candice; Bath, Philip; Broderick, Joseph; Demchuk, Andrew; Donnan, Geoffrey; Durham, Alice; Lavados, Pablo; Lee, Tsong-Hai; Levi, Christopher; Martins, Sheila; Olavarria, Veronica; Pandian, Jeyaraj; Parsons, Mark; Pontes-Neto, Octavio; Ricci, Stefano; Sato, Shoichiro; Sharma, Vijay; Silva, Federico; Song, Lili; Thang, Nguyen; Wardlaw, Joanna; Wang, Ji-Guang; Wang, Xia; Woodward, Mark; Chalmers, John; Robinson, Thompson; ENCHANTED Investigators and CoordinatorsBackground Systolic blood pressure of more than 185 mm Hg is a contraindication to thrombolytic treatment with intravenous alteplase in patients with acute ischaemic stroke, but the target systolic blood pressure for optimal outcome is uncertain. We assessed intensive blood pressure lowering compared with guideline-recommended blood pressure lowering in patients treated with alteplase for acute ischaemic stroke. Methods We did an international, partial-factorial, open-label, blinded-endpoint trial of thrombolysis-eligible patients (age ≥18 years) with acute ischaemic stroke and systolic blood pressure 150 mm Hg or more, who were screened at 110 sites in 15 countries. Eligible patients were randomly assigned (1:1, by means of a central, web-based program) within 6 h of stroke onset to receive intensive (target systolic blood pressure 130–140 mm Hg within 1 h) or guideline (target systolic blood pressure <180 mm Hg) blood pressure lowering treatment over 72 h. The primary outcome was functional status at 90 days measured by shift in modified Rankin scale scores, analysed with unadjusted ordinal logistic regression. The key safety outcome was any intracranial haemorrhage. Primary and safety outcome assessments were done in a blinded manner. Analyses were done on intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01422616. Findings Between March 3, 2012, and April 30, 2018, 2227 patients were randomly allocated to treatment groups. After exclusion of 31 patients because of missing consent or mistaken or duplicate randomisation, 2196 alteplase-eligible patients with acute ischaemic stroke were included: 1081 in the intensive group and 1115 in the guideline group, with 1466 (67·4%) administered a standard dose among the 2175 actually given intravenous alteplase. Median time from stroke onset to randomisation was 3·3 h (IQR 2·6–4·1). Mean systolic blood pressure over 24 h was 144·3 mm Hg (SD 10·2) in the intensive group and 149·8 mm Hg (12·0) in the guideline group (p<0·0001). Primary outcome data were available for 1072 patients in the intensive group and 1108 in the guideline group. Functional status (mRS score distribution) at 90 days did not differ between groups (unadjusted odds ratio [OR] 1·01, 95% CI 0·87–1·17, p=0·8702). Fewer patients in the intensive group (160 [14·8%] of 1081) than in the guideline group (209 [18·7%] of 1115) had any intracranial haemorrhage (OR 0·75, 0·60–0·94, p=0·0137). The number of patients with any serious adverse event did not differ significantly between the intensive group (210 [19·4%] of 1081) and the guideline group (245 [22·0%] of 1115; OR 0·86, 0·70–1·05, p=0·1412). There was no evidence of an interaction of intensive blood pressure lowering with dose (low vs standard) of alteplase with regard to the primary outcome. Interpretation Although intensive blood pressure lowering is safe, the observed reduction in intracranial haemorrhage did not lead to improved clinical outcome compared with guideline treatment. These results might not support a major shift towards this treatment being applied in those receiving alteplase for mild-to-moderate acute ischaemic stroke. Further research is required to define the underlying mechanisms of benefit and harm resulting from early intensive blood pressure lowering in this patient group.Item Prognostic Significance of Hyponatremia in Acute Intracerebral Hemorrhage: Pooled Analysis of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial Studies(Lippincott Williams & Wilkins, 2016) Carcel, Cheryl; Sato, Shoichiro; Zheng, Danni; Heeley, Emma; Arima, Hisatomi; Yang, Jie; Wu, Goujun; Chen, Guofang; Zhang, Shihong; Delcourt, Candice; Lavados, Pablo; Thompson, Robinson; Lindley, Richard; Wang, Xia; Chalmers, John; Anderson, Craig; Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 Investigators.OBJECTIVES: To determine the association of hyponatremia at presentation with clinical and imaging outcomes in patients with acute intracerebral hemorrhage. DESIGN: Retrospective pooled analysis of prospectively collected data from 3,243 participants of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials 1 and 2 (international, multicenter, open, blinded endpoint, randomized controlled trials designed to assess the effects of early intensive blood pressure lowering in patients with acute intracerebral hemorrhage). SETTING: Clinical hospital sites in 21 countries. PATIENTS: Patients with predominantly mild-moderate severity of spontaneous intracerebral hemorrhage within 6 hours of onset and elevated systolic blood pressure (150-220 mm Hg) were included in the study. INTERVENTIONS: Patients were assigned to receive intensive (target systolic blood pressure, < 140 mm Hg within 1 hr) or guideline-recommended (target systolic blood pressure, < 180 mm Hg) blood pressure-lowering therapy. MEASUREMENTS AND MAIN RESULTS: Presentation hyponatremia was defined as serum sodium less than 135 mEq/L. The primary outcome was death at 90 days. Multivariable logistic regression was used to assess the association of hyponatremia with important clinical events. Of 3,002 patients with available data, 349 (12%) had hyponatremia. Hyponatremia was associated with death (18% vs 11%; multivariable-adjusted odds ratio, 1.81; 95% CI, 1.28-2.57; p < 0.001) and larger baseline intracerebral hemorrhage volume (multivariable adjusted, p = 0.046) but not with baseline perihematomal edema volume nor with growth of intracerebral hemorrhage or perihematomal edema during the initial 24 hours. CONCLUSIONS: Hyponatremia at presentation is associated with increased mortality in patients with predominantly deep and modest volume intracerebral hemorrhage through mechanisms that seem independent of growth in intracerebral hemorrhage or perihematomal edema.Item Significance of intraventricular hemorrhage in acute intracerebral hemorrhage: intensive blood pressure reduction in acute cerebral hemorrhage trial results(American Heart Association, Inc., 2015) Chan, Edward; Anderson, Craig; Wang, Xia; Arima, Hisatomi; Saxena, Anubhav; Moullaali, Tom; Heeley, Emma; Delcourt, Candice; Wu, Goujun; Wang, Jinchao; Chen, Guofang; Lavados, Pablo; Stapf, Christian; Thompson, Robinson; Chalmers, John; Huang, Yining; INTERACT2 InvestigatorsBACKGROUND AND PURPOSE: Intraventricular hemorrhage (IVH) with spontaneous intracerebral hemorrhage indicates a poor prognosis but uncertainty exists over the pattern of association. We aimed to elucidate risk associations of IVH and outcome in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) data set. METHODS: INTERACT2 was an international prospective, open-blinded end point, randomized controlled trial in 2839 patients with intracerebral hemorrhage (<6 hours) with elevated systolic blood pressure randomly assigned to intensive (target systolic blood pressure <140 mm Hg) or guideline-based (systolic blood pressure <180 mm Hg) blood pressure management. Associations of baseline IVH in 740 of 2613 (28%) patients and poor outcomes (death and major disability defined on the modified Rankin Scale) at 90 days were determined in linear and logistic regression models. RESULTS: Patients with IVH were significantly older and with greater neurological impairment, history of ischemic stroke, and larger hematomas more often deep hemisphere located at presentation, after adjustment for other baseline variables. Death or major disability occurred in 66% with IVH versus 49% in intracerebral hemorrhage-alone patients (adjusted odds ratio, 1.68; 95% confidence interval, 1.38-2.06; P<0.01). Associations of IVH volume and clinical outcomes were strong and near continuous. Adjusted analyses by thirds of IVH volume indicate thresholds of ≈5 and 10 mL for significantly increased odds of death and death or major disability, respectively. CONCLUSIONS: A strong association exists between the amount of IVH and poor outcome in intracerebral hemorrhage. An IVH volume of 5 to 10 mL emerges as a significant threshold for decision making on prognosis in these patients.