HERMES Meta-Analysis Evaluates Time to Treatment of Endovascular Thrombectomy for Stroke

September 27, 2016—Jeffrey L. Saver, MD, et al published findings from the HERMES trial in the Journal of American Medical Association (JAMA; 2016;316:1279–1288). The meta-analysis evaluated the time to treatment with endovascular thrombectomy and outcomes from ischemic stroke.

The investigators stated that the background of the study is that endovascular thrombectomy with second-generation devices is beneficial for patients with ischemic stroke due to intracranial large-vessel occlusions. Delineation of the association of treatment time with outcomes would help to guide implementation.

The HERMES study sought to characterize the period in which endovascular thrombectomy is associated with benefit and the extent to which treatment delay is related to functional outcomes, mortality, and symptomatic intracranial hemorrhage. 

The investigators pooled demographic, clinical, and brain imaging data, as well as functional and radiologic outcomes, from randomized phase 3 trials involving stent retrievers or other second-generation devices in a peer-reviewed publication (by July 1, 2016). The five identified trials enrolled patients at 89 international sites to compare endovascular thrombectomy plus medical therapy versus medical therapy alone time to treatment.

As reported in JAMA, the primary outcome was degree of disability (modified Rankin Scale [mRS] range, 0–6; lower scores indicating less disability) at 3 months, analyzed with the common odds ratio (cOR) to detect ordinal shift in the distribution of disability over the range of the mRS; secondary outcomes included functional independence at 3 months, mortality by 3 months, and symptomatic hemorrhagic transformation.

The investigators found that among all 1,287 patients (endovascular thrombectomy plus medical therapy [n = 634]; medical therapy alone [n = 653]) enrolled in the five trials (mean age, 66.5 years [standard deviation, 13.1]; women, 47%), time from symptom onset to randomization was 196 minutes (interquartile range [IQR], 142–267). 

Among the endovascular group, symptom onset to arterial puncture was 238 minutes (IQR, 180–302), and symptom onset to reperfusion was 286 minutes (IQR, 215–363). At 90 days, the mean mRS was 2.9 (95% confidence interval [CI], 2.7–3.1) in the endovascular group and 3.6 (95% CI, 3.5–3.8) in the medical therapy group. 

The odds of better disability outcomes at 90 days (mRS distribution) with the endovascular group declined with longer time from symptom onset to arterial puncture: cOR at 3 hours, 2.79 (95% CI, 1.96–3.98; absolute risk difference (ARD) for lower disability scores, 39.2%); cOR at 6 hours, 1.98 (95% CI, 1.3–3; ARD, 30.2%); cOR at 8 hours, 1.57 (95% CI, 0.86–2.88; ARD, 15.7%); retaining statistical significance through 7 hours and 18 minutes. 

In 390 patients who achieved substantial reperfusion with endovascular thrombectomy, each 1-hour delay to reperfusion was associated with a less favorable degree of disability (cOR, 0.84 [95% CI, 0.76–0.93]; ARD, −6.7%) and less functional independence (OR, 0.81 [95% CI, 0.71–0.92], ARD, −5.2% [95% CI, −8.3% to −2.1%]), but no change in mortality (OR, 1.12 [95% CI, 0.93–1.34]; ARD, 1.5% [95% CI, −0.9% to 4.2%]).

The HERMES investigators concluded that in this individual patient data meta-analysis of patients with large-vessel ischemic stroke, earlier treatment with endovascular thrombectomy plus medical therapy compared with medical therapy alone was associated with lower degrees of disability at 3 months; however, the benefit became nonsignificant after 7.3 hours, advised the investigators in JAMA.