Daniel Korya, MD
In an elegant and objective manner, Dr. Saver, from UCLA, published an article in Stroke (2006) quantifying the amount of neurons, synapses and myelinated fibers lost during each hour that a stroke progresses. He further reasoned and specified that in each minute, 1.9 million neurons, 14 billion synapses and 7.5 miles of myelinated fibers are destroyed. This sobering publication reaffirmed the importance of time to reperfusion and provided a numerical backing to the phrase “time is brain”.
Vagal and her colleagues understood the importance of time to reperfusion and designed a study that compared the outcomes of two different reperfusion methods: IV tPA alone versus IV tPA with endovascular treatment. Their study was meant to expand on one of the reasons for failure of the recently published randomized controlled trials comparing IV thrombolysis therapy to endovascular treatment of acute ischemic stroke (IMS III). Critics of IMS III pointed out that endovascular therapy with late reperfusion was bound to be futile, simply because the brain tissue was already infarcted and beyond the time of salvage.
The data for this trial was derived from the IMS III database and medical literature. A subgroup of the IMS III trial patients with large vessel occlusion was used and the TICI score before and after treatment was evaluated to determine the degree of reperfusion. Of the 434 patients randomized to the endovascular arm in IMS III, 240 had complete large vessel occlusions and 175 achieved angiographic reperfusion. The average time to reperfusion in the endovascular arm was 325 minutes. In the IV tPA treatment arm, 83 had large vessel complete occlusion, but there was no follow-up data to determine reperfusion rates.
A decision analytic model was used with effectiveness measured in quality-adjusted life years (QALYs). The modified Rankin Score (mRS) was essentially reduced to favorable versus unfavorable outcome where a 0 represented death and a 1 meant perfect health. The researchers found that when a hypothetical patient presented with a large vessel occlusion and a moderate to severe stroke, endovascular treatment yielded a better outcome if reperfusion could be established within 347 minutes. However, if reperfusion took longer than 347 minutes, than IV tPA alone was better. A 30-minute delay to reperfusion was found to be associated with a 10% relative reduction in good outcome.
When the data were extrapolated and a second order Monte Carlo analysis performed, the conclusion was that for a 10,000 patient population with large vessel moderate to severe ischemic stroke, 78% will achieve a good outcome with endovascular treatment while only 22% can have a good outcome with IV tPA alone.
It should be noted that this study was a post-hoc analysis of data derived from a subpopulation of the primary trial and therefor the findings may not be generalizable. However, these findings warrant further research into the benefits of endovascular treatment for ischemic stroke. The newer devices that were not used in the IMS III trial can achieve faster and more complete reperfusion and could translate into even better outcomes. This study sheds new light on endovascular treatment and may allow for future trials with better designs and higher quality data.