Jong S. Kim

BACKGROUND: Thrombolytic therapy for acute ischemic stroke with a lower-than-standard dose of intravenous alteplase may improve recovery along with a reduced risk of intracerebral hemorrhage. METHODS: Using a 2-by-2 quasi-factorial open-label design, we randomly assigned 3310 patients who were eligible for thrombolytic therapy (median age, 67 years; 63% Asian) to low-dose intravenous alteplase (0.6 mg per kilogram of body weight) or the standard dose (0.9 mg per kilogram); patients underwent randomization within 4.5 hours after the onset of stroke. The primary objective was to determine whether the low dose would be noninferior to the standard dose with respect to the primary outcome of death or disability at 90 days, which was defined by scores of 2 to 6 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]). Secondary objectives were to determine whether the low dose would be superior to the standard dose with respect to centrally adjudicated symptomatic intracerebral hemorrhage and whether the low dose would be noninferior in an ordinal analysis of modified Rankin scale scores (testing for an improvement in the distribution of scores). The trial included 935 patients who were also randomly assigned to intensive or guideline-recommended blood-pressure control. RESULTS: The primary outcome occurred in 855 of 1607 participants (53.2%) in the low-dose group and in 817 of 1599 participants (51.1%) in the standard-dose group (odds ratio, 1.09; 95% confidence interval [CI], 0.95 to 1.25; the upper boundary exceeded the noninferiority margin of 1.14; P=0.51 for noninferiority). Low-dose alteplase was noninferior in the ordinal analysis of modified Rankin scale scores (unadjusted common odds ratio, 1.00; 95% CI, 0.89 to 1.13; P=0.04 for noninferiority). Major symptomatic intracerebral hemorrhage occurred in 1.0% of the participants in the low-dose group and in 2.1% of the participants in the standard-dose group (P=0.01); fatal events occurred within 7 days in 0.5% and 1.5%, respectively (P=0.01). Mortality at 90 days did not differ significantly between the two groups (8.5% and 10.3%, respectively; P=0.07). CONCLUSIONS: This trial involving predominantly Asian patients with acute ischemic stroke did not show the noninferiority of low-dose alteplase to standard-dose alteplase with respect to death and disability at 90 days. There were significantly fewer symptomatic intracerebral hemorrhages with low-dose alteplase. (Funded by the National Health and Medical Research Council of Australia and others; ENCHANTED ClinicalTrials.gov number, NCT01422616.).

The aim of the Part I of Stroke Statistics in Korea is to summarize nationally representative data of the epidemiology and risk factors of stroke in a single document. Every year, approximately 105,000 people experience a new or recurrent stroke and more than 26,000 die of stroke, which indicates that every 5 minutes stroke attacks someone and every 20 minutes stroke kills someone in Korea. Stroke accounts for roughly 1 of every 10 deaths. The estimated stroke prevalence is about 795,000 in people aged ≥30 years. The nationwide total cost for stroke care was 3,737 billion Korean won (US$3.3 billion) in 2005. Fortunately, the annual stroke mortality rate decreased substantially by 28.3% during the first decade of the 21th century (53.2/100,000 in 2010). Among OECD countries, Korea had the lowest in-hospital 30-day case-fatality rate for ischemic stroke and ranked third lowest for hemorrhagic stroke in 2009. The proportion of ischemic stroke has steadily increased and accounted for 76% of all strokes in 2009. According to hospital registry studies, the 90-day mortality rate was 3-7% for ischemic stroke and 17% for intracerebral hemorrhage. For risk factors, among Korean adults ≥30 years of age, one in 3-4 has hypertension, one in 10 diabetes, and one in 7 hypercholesterolemia. One in 3 Korean adults ≥19 years of age is obese. Over the last 10 years, the prevalence of hypertension slightly decreased, but the prevalence of diabetes, hypercholesterolemia, and obesity increased. Smoking prevalence in men has decreased, but is still as high as 48%. This report could be a valuable resource for establishing health care policy and guiding future research directions.

BACKGROUND AND PURPOSE: Cilostazol, a phosphodiesterase inhibitor, has been reported to reduce restenosis rate after coronary angioplasty and stenting. This study was performed to investigate the effect of cilostazol on the progression of intracranial arterial stenosis (IAS). METHODS: We randomized 135 patients with acute symptomatic stenosis in the M1 segment of middle cerebral artery or the basilar artery to either cilostazol 200 mg per day or placebo for 6 months. Aspirin 100 mg per day was also given to all patients. Patients with potential embolic sources in the heart or extracranial arteries were excluded. IAS was assessed by magnetic resonance angiogram (MRA) and transcranial Doppler (TCD) at the time of recruitment and 6 months later. The primary outcome was the progression of symptomatic IAS on MRA and secondary outcomes were clinical events and progression on TCD. RESULTS: Thirty-eight patients were prematurely terminated. Dropout rates and reasons for dropouts were similar between the cilostazol and placebo groups. There was no stroke recurrence in either cilostazol or placebo group, but there was 1 death and 2 coronary events in each group. In cilostazol group, 3 (6.7%) of 45 symptomatic IAS progressed and 11 (24.4%) regressed. In placebo group, 15 (28.8%) of symptomatic IAS progressed and 8 (15.4%) regressed. Progression of symptomatic IAS in cilostazol group was significantly lower than that in placebo group (P=0.008) CONCLUSIONS: Our study suggests that symptomatic IAS is a dynamic lesion and cilostazol may prevent its progression.