2019年神经内科十大临床研究突破

1.N Engl J Med+Lancet—改变指南：最新研究支持卒中后4.5-9小时采取静脉溶栓对某些患者是有益处的

英文摘要1：

BACKGROUND:

Strokethrombolysis with alteplase is currently recommended 0-4·5 h after strokeonset. We aimed to determine whether perfusion imaging can identify patientswith salvageable brain tissue with symptoms 4·5 h or more from stroke onset orwith symptoms on waking who might benefit from thrombolysis.

METHODS:

Inthis systematic review and meta-analysis of individual patient data, wesearched PubMed for randomised trials published in English between Jan 1, 2006,and March 1, 2019. We also reviewed the reference list of a previous systematicreview of thrombolysis and searched ClinicalTrials.gov for interventionalstudies of ischaemic stroke. Studies of alteplase versus placebo in patients(aged ≥18years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-upstroke, who were imaged with perfusion-diffusion MRI or CT perfusion wereeligible for inclusion. The primary outcome was excellent functional outcome(modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline ageand clinical severity. Safety outcomes were death and symptomatic intracerebralhaemorrhage. We calculated odds ratios, adjusted for baseline age and NationalInstitutes of Health Stroke Scale score, using mixed-effects logisticregression models. This study is registered with PROSPERO, numberCRD42019128036.

FINDINGS:

Weidentified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND,and EPITHET. Of the 414 patients included in the three trials, 213 (51%) wereassigned to receive alteplase and 201 (49%) were assigned to receive placebo.Overall, 211 patients in the alteplase group and 199 patients in the placebogroup had mRS assessment data at 3 months and thus were included in theanalysis of the primary outcome. 76 (36%) of 211 patients in the alteplasegroup and 58 (29%) of 199 patients in the placebo group had achieved excellentfunctional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI1·15-2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common inthe alteplase group than the placebo group (ten [5%] of 213 patients vs one[<1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI1·23-76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18(9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81-2·96,p=0·66).

INTERPRETATION:

Patientswith ischaemic stroke 4·5-9 h from stroke onset or wake-up stroke withsalvageable brain tissue who were treated with alteplase achieved betterfunctional outcomes than did patients given placebo. The rate of symptomaticintracerebral haemorrhage was higher with alteplase, but this increase did notnegate the overall net benefit of thrombolysis.

英文摘要2：

BACKGROUND:

Thetime to initiate intravenous thrombolysis for acute ischemic stroke isgenerally limited to within 4.5 hours after the onset of symptoms. Some trialshave suggested that the treatment window may be extended in patients who areshown to have ischemic but not yet infarcted brain tissue on imaging.

METHODS:

Weconducted a multicenter, randomized, placebo-controlled trial involvingpatients with ischemic stroke who had hypoperfused but salvageable regions ofbrain detected on automated perfusion imaging. The patients were randomlyassigned to receive intravenous alteplase or placebo between 4.5 and 9.0 hoursafter the onset of stroke or on awakening with stroke (if within 9 hours fromthe midpoint of sleep). The primary outcome was a score of 0 or 1 on themodified Rankin scale, on which scores range from 0 (no symptoms) to 6 (death),at 90 days. The risk ratio for the primary outcome was adjusted for age andclinical severity at baseline.

RESULTS:

After225 of the planned 310 patients had been enrolled, the trial was terminatedbecause of a loss of equipoise after the publication of positive results from aprevious trial. A total of 113 patients were randomly assigned to the alteplasegroup and 112 to the placebo group. The primary outcome occurred in 40 patients(35.4%) in the alteplase group and in 33 patients (29.5%) in the placebo group(adjusted risk ratio, 1.44; 95% confidence interval [CI], 1.01 to 2.06;P = 0.04). Symptomatic intracerebral hemorrhage occurred in 7 patients (6.2%)in the alteplase group and in 1 patient (0.9%) in the placebo group (adjustedrisk ratio, 7.22; 95% CI, 0.97 to 53.5; P = 0.05). A secondary ordinal analysisof the distribution of scores on the modified Rankin scale did not show asignificant between-group difference in functional improvement at 90 days.

CONCLUSIONS: