早期溶栓可使轻中度脑卒中患者获益

芬兰赫尔辛基大学中心医院的Daniel Strbian医生及其同事在8月22日的《脑卒中》(Stroke)杂志上报告称，早期静脉溶栓治疗似乎可使中度和轻度脑卒中患者获益，但尚未完全明确轻度患者的获益是否为基线脑卒中严重程度较低所致。尽管如此，可能的话，轻度或中度症状患者应在症状发生后90分钟内甚至更早的时间接受溶栓治疗 (doi: 10.1161/STROKEAHA.111.000819)。

该研究建立在作者之前对于症状发生后70分钟内给予超早期溶栓治疗的单中心分析的基础之上，后者显示重度脑卒中患者的3个月结局显著改善。但他们指出：“并非所有患者都能从早期IV溶栓治疗中获得相同的益处……我们旨在利用一个大型多中心数据集，探索额外获益在不同脑卒中严重程度亚组的急性缺血性脑卒中患者中的分布是否均衡。”但在该队列中的878例患者中，仅有6%获得 超早期治疗。因此，将这项新的分析扩展至检验在90分钟内接受治疗的患者的结局。“这只是一个相对时间点，因为与90分钟或更短时间相比，在91~180分钟之间开始接受治疗的患者中，需治数由4.5增加至9，翻了1倍。”

这项多中心分析包含了在4个脑卒中中心接受治疗的6,856例患者，其中19%在症状发生后90分钟内接受治疗。患者平均年龄为72岁。平均基线国立卫生研究院脑卒中评分(NIHSS)为1；评分为轻度、中度和重度的患者各占1/3。

结果显示，与较晚接受治疗相比，中度症状患者在90分钟或更短时间内接受治疗与3个月结局优良相关，结局优良定义为mRS评分为0~1（比值比为1.37）。在重度症状(OR，1.00)或轻度症状(OR，1.04)患者中未见这种获益。然而，作者指出，轻度症状患者未获益可能与基线时病生理变化严重程度较轻有关。为了排除这种可能性，他们进行了一项亚组分析，限定3个月结局的最佳可能指标为mRS评分为0。结果显示，获得早期治疗的患者达到这一结局的可能性增加51%(OR，1.51)。早期治疗还与颅内出血发生率明显较低(14.8% vs. 17.6%)和症状性颅内出血发生率略低(3.7% vs. 4.5%)有关。早期治疗与死亡率无关，这与作者之前的研究结果存在矛盾。“这可能是因为目前这一队列中接受超早期治疗的患者数量较少。”

研究结论为，早期静脉溶栓治疗可能使中度和轻度脑卒中患者的3个月结局得到改善。

Strbian披露无相关利益冲突。但19位合著者中的10位报告与制药企业之间存在多种利益关系。

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By: MICHELE G. SULLIVAN, Cardiology News Digital Network

Early intravenous thrombolysis appears to benefit patients with moderate stroke as well as those with mild stroke, although it’s not completely clear if the benefit in mild patients is due more to the lower baseline stroke severity.

Nevertheless, patients with mild or moderate symptoms should get thrombolytic treatment as early as possible within 90 minutes of symptom onset and even earlier, if possible, Dr. Daniel Strbian and his colleagues reported in the Aug. 22 issue of Stroke (doi: 10.1161/STROKEAHA.111.000819).

Those with mild symptoms and early treatment were 51% more likely to have excellent 3-month outcomes, defined as a modified Rankin Scale (mRS) score of 0, in a secondary analysis of the study, reported Dr. Strbian of Helsinki University Central Hospital, Finland, and his coauthors.

The study builds on the authors’ previous single-center analysis of ultra-early thrombolytic treatment delivered within 70 minutes of symptom onset, which found significantly improved 3-month outcomes in patients with severe stroke. But, they noted, "because not all patients benefit from early IV thrombolysis equally ... we aimed to explore, in a large multicenter dataset, whether the extra benefit is distributed equally among predefined stroke severity subgroups of acute ischemic stroke patients."

However, only 6% of the 878 patients in that cohort got the ultra-early treatment. Therefore, the new analysis was expanded to examine outcomes in patients treated within 90 minutes. "This is a relevant time-point, because the number needed to treat doubles from 4.5 to 9 for patients with [treatment initiation of] 91-180 minutes, compared with ... 90 minutes or less."

The multicenter analysis comprised 6,856 patients treated at four stroke centers; 19% of these received treatment within 90 minutes of symptom onset.

Patients had a mean age of 72 years. The mean baseline National Institutes of Health Stroke Score (NIHSS) was 11; the score was mild in one-third of patients, moderate in one-third, and severe in one-third.

Compared with later treatment, treatment within 90 minutes or less for patients with moderate symptoms was significantly associated with excellent 3-month outcomes, defined as an mRS score of 0-1 (odds ratio, 1.37). This benefit was not seen in patients with severe symptoms (OR, 1.00), or in those with mild symptoms (OR, 1.04).

However, the authors noted, the lack of benefit for patients with mild symptoms may have been influenced by their less severe pathophysiology at baseline. To offset this possibility they conducted a subanalysis, restricting 3-month outcomes to the best possible measurement  an mRS of 0. Patients who got the early treatment were 51% more likely to achieve this outcome than were those treated outside the 90-minute window (OR, 1.51).

The early treatment was also associated with a significantly lower proportion of any intracranial hemorrhage (14.8% vs. 17.6%), and a nonsignificantly lower proportion of symptomatic intracranial hemorrhage (3.7% vs. 4.5%).

Early treatment was not associated with mortality a finding contrary to the authors’ prior study. "This may be because of the limited number of patients treated ultra-early in the current cohort," they said.

Dr. Strbian reported no financial disclosures. However, 10 of the 19 coauthors did report multiple relationships with pharmaceutical companies.