IMS III: Adding Endovascular Therapy to IV tPA Boosts Function, QoL After Severe Stroke

Endovascular therapy boosts quality of life (QoL) and functional outcomes in patients with severe stroke over IV tissue plasminogen activator (tPA) alone, according to a recent analysis of IMS III. The study, published online April 9, 2015, ahead of print in Stroke, is the latest in a string of reports contradicting earlier negative trials of endovascular stroke therapy and suggesting that differences become apparent with longer follow-up.

The IMS III trial, which was halted early due to futility, looked at more than 600 patients with acute moderate-to-severe ischemic stroke (NIH Stroke Scale [NIHSS] score ≥ 8) who presented within 3 hours of symptom onset at 58 centers in North America, Europe, and Australia between 2006 and 2012. Patients were randomly assigned to tPA followed by endovascular treatment (n = 434) or tPA alone (n = 222). There was no difference between treatment groups in the primary endpoint of favorable functional outcome at 3 months.

For the new study, IMS III investigators led by Joseph P. Broderick, MD, of the University of Cincinnati Neuroscience Institute (Cincinnati, OH), examined function and QoL out to 12 months using the modified Rankin Scale (mRS) and the Euro-QoL 5D questionnaire, which covers mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.

No Advantage to Endovascular in Moderately Severe Cases

Overall, 428 patients were classified as having moderately severe stroke (NIHSS score 8-19) and 201 as having severe stroke (NIHSS score ≥ 20).

Among patients with severe stroke, more of those in endovascular group had an mRS score of 0-2 at 12 months than in the tPA alone group (32.5% vs 18.6%; P = .037). However, there was no difference between treatment groups among patients with moderately severe stroke. Overall, the odds of favorable outcomes with endovascular therapy were more than twice that of the tPA alone group in unadjusted (P = .026) as well as adjusted analyses (P = .028) over 12-month follow-up.

Responses to the EQ-5D were used to calculate quality-adjusted days in the post-stroke period. Based on this assessment, patients in the severe stroke group who received endovascular therapy had 35.2 more days of quality-adjusted life over the 12-month period than those who received tPA alone (mean of 145.8 vs 110.6 days). Again, no such difference was seen in those with moderately severe strokes (mean of 212.6 vs 211.1 days).

According to Dr. Broderick and colleagues, the results are in line with the endovascular benefits demonstrated in patients with severe stroke in MR CLEAN, ESCAPE, EXTEND IA, and SWIFT PRIME.

The researchers add that the “inability to demonstrate a major arterial occlusion before enrollment in IMS III in those patients with an NIHSS < 20 is one major explanation for lack of benefit in IMS III, particularly because IMS III and the other endovascular trials were consistent in their outcomes for the subgroup of patients with an NIHSS ≥ 20, even with differences in the use of endovascular technology and other patient selection criteria.” IMS III patients with severe stroke “not only have large artery occlusions,” they say, “but also have large areas of ischemic brain, some of which is potentially salvageable with timely reperfusion.”

Narrowing Down Who Benefits the Most

In a telephone interview with TCTMD, Philip M. Meyers, MD, of Columbia University Medical Center (New York, NY), said the data are one more step toward understanding stroke recovery and defining the patient population most likely to benefit from endovascular stroke therapy.

“Although the IMS III trial failed to demonstrate the outcome benefit of endovascular treatment in the overall trial population, these data further support the notion that there is a subgroup of patients who do experience a real benefit from endovascular treatment in both shorter- and longer-term outcomes,” he said. “The latest group of stroke trials has defined this subgroup as patients with the most severe strokes; large artery occlusions; small, completed infarcts at the time of presentation; and good collateral blood supply. This is a subset of individuals with acute ischemic stroke—perhaps a more circumscribed target population for endovascular intervention than we had once considered.”

Both Dr. Meyers and the study authors say more research is needed to understand why the moderately severe group did not derive benefit.

“The most likely explanation is that smaller strokes, manifested by less severe neurologic impairment initially, have more brain that will survive the event, demonstrate better neuroplasticity, or respond better to noninterventional treatment,” Dr. Meyers added. “These data further support the concept that appropriate patient selection, treatment by highly experienced and skilled clinicians, and intensive stroke rehabilitation over many months yields more patients who demonstrate good recovery. We are not generating larger numbers who are severely disabled by these interventions.”

Additionally, Dr. Meyers said the ideal duration of follow-up also is being redefined, a step that will likely impact future trials of endovascular stroke therapy. “A 3-month endpoint may not be adequate. We really must consider endpoints for these patients that extend farther into the future and to redouble our efforts to help them recover,” he concluded.

Palesch YY, Yeatts SD, Tomsick TA, et al. Twelve-month clinical and quality-of-life outcomes in the Interventional Management of Stroke III trial. Stroke. 2015;Epub ahead of print.

Disclosures:

Dr. Broderick reports receiving research support to his institution from Genentech for the PRISMS trial and travel compensation from Boehringer Ingelheim.

Dr. Meyers reports no relevant conflicts of interest.

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