Endovascular Therapy Beats Thrombolysis for Improving Function After Stroke


Take Home: Endovascular Therapy Beats Thrombolysis for Improving Function After Stroke Patients with acute ischemic stroke fare better in terms of functional outcomes when they are treated with endovascular therapy with a thrombectomy device than with standard fibrinolysis management, according to a meta-analysis published in the November 3, 2015 issue of the Journal of the American Medical Association. Furthermore, the meta-analysis provides confirmation of factors that may optimize outcomes with the rapidly growing therapy. 

Saleh A. Almenawer, MD, of McMaster University (Hamilton, Canada), and colleagues examined data from 8 multicenter clinical trials published between 2013 and 2015 that randomized a total of 2,423 patients (mean age, 67.4 years; 46.7% women) to endovascular therapy with mechanical thrombectomy (n = 1,313) or standard medical management (n = 1,110), which included tPA. Time from stroke onset to endovascular therapy varied from 5 to 12 hours (mean time, 3.8 hours). 

The 8 included trials were:

Compared with those who received standard therapy, patients who underwent endovascular thrombectomy had higher rates of angiographic revascularization at 24 hours (75.8% vs 34.1%; P < .001). Endovascular therapy patients also had a greater proportional treatment benefit across Modified Rankin scale (mRS) scores at 90 days (primary outcome) and increased functional independence. There were no differences between the endovascular or standard therapy arms in rates of intracranial hemorrhage or all-cause mortality at 90 days (table 1). Morbidity, including rates of in-hospital medical complications, also was not different. Importantly, there was substantial heterogeneity among trials for the outcome of functional improvement.

Table 1. Endovascular Therapy vs Standard Therapy

In sensitivity analyses, functional outcomes were better among patients who had CT angiographic imaging performed to confirm proximal arterial occlusion vs those who did not. Additionally, adding tPA to endovascular therapy, and using stent retrievers instead of first-generation devices also resulted in better functional outcomes.

Table 2. Sensitivity Analyses for Functional Improvement

All Answers Still Not In

Three of the 8 trials (SYNTHESIS, MR RESCUE, and IMS III) failed to show any difference in outcomes but were widely criticized for inconsistent use of vascular imaging prior to randomization, variable use of tPA, and use of less effective and older-generation mechanical devices, Almenawer and colleagues note.

A number of key questions remain unanswered, including the importance of time to treatment in quantifying results of endovascular therapy. Almenawer and colleagues suggest that “it would be prudent to define a precise maximal time window after which treatment is considered relatively futile, similar to what exists for intravenous tPA (< 4.5 hours).”

In a telephone interview with TCTMD, IMS III’s lead investigator Joseph P. Broderick, MD, of the University of Cincinnati (Cincinnati, OH), said while the meta-analysis is well done and included negative as well as positive trials, it is essentially a replication of what the individual trials showed and “doesn’t add a great deal beyond what was included in the update to the AHA guidelines for endovascular therapy published in July.”

Broderick added that the outcomes of the sensitivity analyses do not change anything that is currently in the guidelines, and noted that there are a number of unanswered questions.

Patient Selection Issues

In an editorial accompanying the study, Joanna M. Wardlaw, MD, and Martin S. Dennis, MD, of the University of Edinburgh (Edinburgh, United Kingdom), address several of those unknowns, including how many patients with acute stroke may be eligible for endovascular therapy and which hospitals should perform it. Overall, they estimate that about 7% or more of ischemic stroke patients may be eligible, but caution that multi-disciplinary teams and careful coordination will be necessary to ensure that the right patients are treated and that they receive high-quality aftercare.

Broderick added that the optimal use of imaging to select patients for endovascular therapy is another ongoing question, as is “whether there are other things that can be added to endovascular therapy or tweaked to improve outcomes.” Examples include adding agents to tPA (ie, anticoagulants, antithrombotics, or antiplatelet agents such as eptifibatide), testing out newer forms of tPA such as TNK-tPA, and using hypothermia in patients with larger strokes, he added.

While some of these questions may not be answered for years, Broderick said the studies included in the meta-analysis have resulted in a huge step forward in the treatment of acute stroke. But, he added, “we need to fine tune it and figure out how long we have…because we know there may be some people in whom there is enough brain that’s still at risk but not yet dead that opening up the artery can still make a difference.”


Sources: 
1. Badhiwala JH, Nassiri F, Alhazzani W, et al. Endovascular thrombectomy for acute ischemic stroke a: meta-analysis. JAMA. 2015;314:1832-1843.
2. Wardlaw JM, Dennis MS. Thrombectomy for acute ischemic stroke [editorial]. JAMA. 2015;314:1803-1805. 

Disclosures:

  • Almenawer, Wardlaw, and Dennis report no relevant conflicts of interest. 
  • Broderick reports receiving research grants from Genentech for the PRISMS study. 

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