Chunjuan Wang

Significant Underuse of Warfarin in Patients with Nonvalvular Atrial Fibrillation: Results from the China National Stroke Registry

BACKGROUND Warfarin reduces the risk of stroke in patients with atrial fibrillation (AF) but is often underused in clinical practice. We aimed to examine the current state of warfarin use in nonvalvular atrial fibrillation (NVAF) patients with first-ever ischemic stroke (IS) or transient ischemic attack (TIA) in China and to analysis factors causing such underuse. METHODS By accessing the China National Stroke Registry, data on consecutive patients with known NVAF who developed first-ever IS or TIA were studied. Proportion of warfarin use was estimated in those patients with known NVAF who should be eligible for anticoagulation therapy. Factors associated with warfarin underuse were identified by multivariate logistic regression. RESULTS Of 11,080 patients with first-ever IS or TIA, 996 (9.7%) had NVAF and no contraindications to anticoagulation therapy and 592 of them had history of AF. Among these patients, only 96 (16.2%) were on warfarin and 496 (83.8%) were not. In those patients on warfarin, only 1 of his international normalized ratios on admission was in the therapeutic range of 2.0-3.0. Based on the CHADS2 scores, about 20.2% low-risk AF patients took warfarin; however, only 15.2% moderate and 16.4% high-risk patients were on warfarin. Older patients and patients with history of coronary heart disease (CHD) were less likely to be given warfarin, whereas patients with history of prestroke antiplatelet use were more likely to take warfarin. CONCLUSIONS We found that warfarin was significantly underused in patients with known NVAF in China. Age and CHD and prestroke antiplatelet therapy were related factors.

Standard-Dose Intravenous Tissue-Type Plasminogen Activator for Stroke Is Better Than Low Doses

Background and Purpose— It remains uncertain whether lower dose intravenous tissue-type plasminogen activator (tPA) for stroke is as effective and safe as the standard dose. Methods— We analyzed data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China). Patients who were treated within 4.5 hours after symptom onset were included. These patients were divided into 5 groups according to tPA doses given: <0.5, 0.5 to 0.7, 0.7 to 0.85, 0.85 to 0.95, and ≥0.95 mg/kg. Symptomatic intracranial hemorrhage, mortality, and 90-day outcome assessed by modified Rankin scale were analyzed. Results— A total of 919 patients were enrolled. Among them, 9 had <0.5 mg/kg, 75 had 0.5 to 0.7 mg/kg, 131 had 0.7 to 0.85 mg/kg, 678 had 0.85 to 0.95 mg/kg, and 26 had ≥0.95 mg/kg. Because of sample sizes, only 0.5 to 0.7, 0.7 to 0.85, and 0.85 to 0.95 mg/kg groups were compared. Median tPA doses were 0.64, 0.79, and 0.90 mg, respectively. After adjustment for the baseline variables, there were no significant differences in mortality(5.41% versus 8.66% versus 7.36%; P=0.695) and symptomatic intracranial hemorrhage (0% versus 3.82% versus 1.46%; P=0.106). The 0.5 to 0.7 mg/kg group had less excellent recovery outcome (modified Rankin scale, 0–1) than 0.85 to 0.95 mg/kg group (41.89% versus 53.83%; odds ratio=0.58; P=0.031) at 90 days. The 0.70 to 0.85 mg/kg group had less functional independence outcome (modified Rankin scale, 0–2) than 0.85 to 0.95 mg/kg group (54.33% versus 64.51%; odds ratio=0.66; P=0.036) at 90 days. Conclusions— Our study suggests that standard-dose intravenous tPA for stroke had more favorable outcome without increasing the risk of symptomatic intracranial hemorrhage than low-dose tPA. For Asian people, 0.9 mg/kg should be the optimal dose of tPA to treat acute ischemic stroke.

Implementation and Outcome of Thrombolysis with Alteplase 3 to 4.5 h After Acute Stroke in Chinese Patients

The European Cooperative Acute Stroke Study (ECASS) III showed that intravenous recombinant tissue plasminogen activator (rtPA) administered in the 3 to 4.5 h after symptom onset significantly improved clinical outcomes in patients with acute ischemic stroke (AIS). But little is known regarding the safety and efficacy of intravenous rtPA treatment within this extended time window in Chinese patients with AIS.

Use of Warfarin at Discharge Among Acute Ischemic Stroke Patients With Nonvalvular Atrial Fibrillation in China

Background and Purpose— Guidelines recommend oral anticoagulation for ischemic stroke patients with atrial fibrillation, and previous studies have shown the underuse of anticoagulation for these patients in China. We sought to explore the underlying reasons and factors that currently affect the use of warfarin in China. Methods— From June 2012 to January 2013, 19 604 patients with acute ischemic stroke were admitted to 219 urban hospitals voluntarily participating in the China National Stroke Registry II. Multivariable logistic regression models using the generalized estimating equation method were used to identify patient/hospital factors independently associated with warfarin use at discharge. Results— Among the 952 acute ischemic stroke patients with nonvalvular atrial fibrillation, 19.4% were discharged on warfarin. The risk of bleeding (52.8%) and patient refusal (31.9%) were the main reasons for not prescribing anticoagulation. Larger/teaching hospitals were more likely to prescribe warfarin. Older patients, heavy drinkers, patients with higher National Institutes of Health Stroke Scale score on admission were less likely to be given warfarin, whereas patients with history of heart failure and an international normalized ratio between 2.0 and 3.0 during hospitalization were significantly associated with warfarin use at discharge. Conclusions— The rate of warfarin use remains low among patients with ischemic stroke and known nonvalvular atrial fibrillation in China. Hospital size and academic status together with patient age, heart failure, heavy alcohol drinking, international normalized ratio in hospital, and stroke severity on admission were each independently associated with the use of warfarin at discharge. There is much room for improvement for secondary stroke prevention in nonvalvular atrial fibrillation patients in China.

HbA1c is associated with increased all-cause mortality in the first year after acute ischemic stroke

Abstract Objectives: To assess the association between baseline HbA1c and the poor outcomes within 1 year after acute ischemic stroke. Methods: Acute ischemic stroke patients with HbA1c values at baseline (n  =  2186) were selected from the abnormal glucose regulation in patients with acute stroke across China study (ACROSS). Logistic regressions were performed to assess the association between HbA1c quartiles (<5·5% [37 mmol/mol], 5·5 to <6·1% [37 to <43 mmol/mol], 6·1 to <7·2% [43 to <55 mmol/mol], and ≥7·2% [≥55 mmol/mol]) and the poor outcomes within 1 year. Poor outcomes were defined as all-cause mortality (modified Rankin scale [mRS]  =  6) and poor functional outcome (mRS [2–6]). Results: The risk for all-cause mortality was significantly increased in HbA1c level >5·5% [>37 mmol/mol] when compared to HbA1c quartile <5·5% [<37 mmol/mol] and dramatically increased to two to three times higher in the highest HbA1c quartile ≥7·2% [>55 mmol/mol] (1-year all-cause mortality model, odds ratios [ORs] were 1·07, 1·01, and 2·45, P for trend 0·009). After the further analysis with previous diabetes mellitus (DM) and post-stroke insulin use stratified, the risk of mortality was increased across the HbA1c levels (P for trend 0·020) and dramatically augmented in HbA1c ≥7·2% [>55 mmol/mol] in patients without a history of DM and without post-stroke insulin use. Discussion: Elevated HbA1c (from 5·5% [37 mmol/mol]) presenting pre-stroke glycemia status has a significant trend in increasing the risk of 1-year all-cause mortality. HbA1c ≥7·2% (>55 mmol/mol) is an independent risk predictor for 1-year all-cause mortality after acute first-ever ischemic stroke. Such an association might be altered by glycometabolism status.

Risk factors for poor outcome and mortality at 3 months after the ischemic stroke in patients with atrial fibrillation.

BACKGROUND It has been shown that patients with atrial fibrillation have a poor prognosis in the early recovery phase after ischemic stroke (IS) or transient ischemic attack (TIA). The purpose of this study was to identify the risk factors associated with poor outcome, including mortality, 3 months after the onset of IS in patients with atrial fibrillation. METHODS We have prospectively investigated the characteristics of patients selected from the China National Stroke Registry. Poor outcome was defined as the modified Rankin scale score of 3 or more or death at 3-month follow-up. Association between the relevant risk factors and poor outcome was analyzed using logistic regression analysis. Additionally, the interaction between multiple risk factors was also analyzed. RESULTS Each year of age (odds ratio [OR]: 1.031; 95% confidence interval [CI] 1.017-1.045), the National Institutes of Health Stroke Scale (NIHSS) at admission (OR: 1.219; 95% CI 1.185-1.254), and female gender (OR: 1.710; 95% CI 1.296-2.256) were independent risk factors for poor outcome at 3 months after IS. Independent risk factors for 3-month mortality included age (OR: 1.024; 95% CI 1.007-1.041), NIHSS at admission (OR: 1.122; 95% CI 1.100-1.144), and history of heart failure (OR: 1.855; 95% CI 1.141-3.015). Conversely, heavy alcohol intake was associated with protective effect on mortality poststroke (OR: .400; 95% CI .173-.928). There was no significant interaction between age and gender (for mortality, P=.16; for poor outcomes, P=.91), age and NIHSS (for mortality, P=.38; for poor outcomes, P=.11), and gender and NIHSS (for mortality, P=.33; for poor outcomes, P=.80). CONCLUSIONS Age, gender, and NIHSS score were independently associated with poor outcome for IS or TIA patients with nonvalvular atrial fibrillation in the early recovery stage.

Substantial progress yet significant opportunity for improvement in Stroke Care in China

Background and Purpose— Stroke is a leading cause of death in China. Yet the adherence to guideline-recommended ischemic stroke performance metrics in the past decade has been previously shown to be suboptimal. Since then, several nationwide stroke quality management initiatives have been conducted in China. We sought to determine whether adherence had improved since then. Methods— Data were obtained from the 2 phases of China National Stroke Registries, which included 131 hospitals (12 173 patients with acute ischemic stroke) in China National Stroke Registries phase 1 from 2007 to 2008 versus 219 hospitals (19 604 patients) in China National Stroke Registries phase 2 from 2012 to 2013. Multiple regression models were developed to evaluate the difference in adherence to performance measure between the 2 study periods. Results— The overall quality of care has improved over time, as reflected by the higher composite score of 0.76 in 2012 to 2013 versus 0.63 in 2007 to 2008. Nine of 13 individual performance metrics improved. However, there were no significant improvements in the rates of intravenous thrombolytic therapy and anticoagulation for atrial fibrillation. After multivariate analysis, there remained a significant 1.17-fold (95% confidence interval, 1.14–1.21) increase in the odds of delivering evidence-based performance metrics in the more recent time periods versus older data. The performance metrics with the most significantly increased odds included stroke education, dysphagia screening, smoking cessation, and antithrombotics at discharge. Conclusions— Adherence to stroke performance metrics has increased over time, but significant opportunities remain for further improvement. Continuous stroke quality improvement program should be developed as a national priority in China.

Unfavorable Outcome of Thrombolysis in Chinese Patients with Cardioembolic Stroke: a Prospective Cohort Study

Thrombolysis with alteplase is an effective and safe treatment for acute ischemic stroke (AIS). It is controversial whether the outcome of thrombolysis in cardioembolic stroke is different from that of other stroke subtypes. This study compares the outcomes at 3 months postthrombolysis in Chinese patients with AIS secondary to cardioembolism (CE) to the outcomes of those with large‐artery atherosclerosis (LAA).

Treatment Effect of Clopidogrel Plus Aspirin Within 12 Hours of Acute Minor Stroke or Transient Ischemic Attack

Background The aim of this study was to analyze the benefits and safety associated with the combination therapy of clopidogrel and aspirin among minor stroke or transient ischemic attack patients treated within 12 hours. Methods and Results This was a subanalysis of the CHANCE (Clopidogrel in High‐Risk Patients with Acute Nondisabling Cerebrovascular Events) trial, mainly limited to the prespecified group of patients randomized within 12 hours to either the combination of clopidogrel plus aspirin or aspirin alone. The primary outcome was ischemic stroke during 90‐day follow‐up. Recurrent ischemic stroke and progressive ischemic stroke were analyzed. Multivariable Cox modeling showed that randomization within 12 hours was an independent predictor of ischemic stroke events (hazard ratio [95% CI] 1.25 [1.04–1.49], P=0.02). Among 2573 patients randomized within 12 hours, 282 (10.96%) patients had ischemic stroke events. Among them, 158 (12.34%) of 1280 patients taking aspirin experienced ischemic stroke compared with 124 (9.59%) of 1293 patients taking clopidogrel–aspirin (P=0.02). The dual antiplatelet was more effective than aspirin alone in reducing the risk of recurrent ischemic stroke (6.57% versus 8.91%, P=0.03) but not progressive ischemic stroke (3.02% versus 3.43%, P=0.28). There was no significant difference in hemorrhagic events (P=0.39). Conclusions Among patients treated within 12 hours, the combination of clopidogrel and aspirin was more effective than aspirin alone in reducing the risk of recurrent ischemic stroke during the 90‐day follow‐up and did not increase the hemorrhagic risk. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00979589.

Cost-effectiveness of thrombolysis within 4.5 hours of acute ischemic stroke in China.

Background Previous economic studies conducted in developed countries showed intravenous tissue-type plasminogen activator (tPA) is cost-effective for acute ischemic stroke. The present study aimed to determine the cost-effectiveness of tPA treatment in China, the largest developing country. Methods A combination of decision tree and Markov model was developed to determine the cost-effectiveness of tPA treatment versus non-tPA treatment within 4.5 hours after stroke onset. Outcomes and costs data were derived from the database of Thrombolysis Implementation and Monitor of acute ischemic Stroke in China (TIMS-China) study. Efficacy data were derived from a pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Costs and quality-adjusted life-years (QALYs) were compared in both short term (2 years) and long term (30 years). One-way and probabilistic sensitivity analyses were performed to test the robustness of the results. Results Comparing to non-tPA treatment, tPA treatment within 4.5 hours led to a short-term gain of 0.101 QALYs at an additional cost of CNY 9,520 (US