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In patients with acute ischemic stroke undergoing contemporary endovascular therapy, timely treatment and achievement of successful revascularization are key to good functional outcome and reduced mortality at 3 months, according to a large registry study published online March 4, 2014, ahead of print in Stroke.

Investigators led by Sònia Abilleira, MD, PhD, of the Agency for Health Quality and Assessment of Catalonia (Barcelona, Spain), analyzed data from 536 patients with acute ischemic stroke who received endovascular therapy at 7 comprehensive stroke centers between January 2011 and December 2012 and were enrolled in the Catalonian SONIIA registry. Of this cohort, 285 patients (53%) received IV thrombolysis at a referring hospital; the remaining 251 patients (46.8%), who were either refractory to or ineligible for IV thrombolysis, received endovascular therapy alone.

Endovascular therapy consisted of mechanical thrombectomy in 90.5% of patients, combined pharmacological-mechanical approaches in 7.5%, and intra-arterial thrombolysis in 2.0%. The median time from symptom onset to groin puncture was 277 minutes.

Overall, 73.9% of interventions resulted in successful revascularization (modified Thrombolysis In Cerebral Infarction [TICI] score 2b/3). Symptomatic cerebral bleeding was observed in 5.6% of patients. At 3 months, 22.2% of patients had died; among survivors, 43.3% had achieved good functional outcomes (modified Rankin score ≤ 2).

Key Positive, Negative Factors Identified

Patients were divided into multiple dichotomous subgroups based on demographic and procedural characteristics to tease out contributors to outcomes.

On logistic regression analysis, achievement of successful revascularization (OR 8.12; P < 0.001) and the presence of A-fib (OR 1.85; P = 0.010) predicted increased likelihood of functional independence at 3 months, while greater stroke severity (National Institutes of Health Stroke Scale [NIHSS] score > 14; OR 0.14; P < 0.001), hypertension (OR 0.49; P = 0.001), and age greater than 80 years (OR 0.21; P < 0.001) reduced the chances of a good functional outcome.

With regard to mortality, age greater than 80 years (OR 1.81; P = 0.049) and hypertension (OR 2.04; P = 0.006) predicted increased risk, while anterior circulation strokes (OR 0.38; P = 0.005) and prestroke modified Rankin score < 2 (OR 0.39; P = 0.015) reduced risk.

In addition, patients who achieved revascularization had lower rates of symptomatic cerebral hemorrhage than those without revascularization (3% vs 12.9%; P < 0.001).

According to the authors, because revascularization is also an intermediate outcome, a separate model was constructed without this variable. This model retained the independent predictors mentioned above in addition to the variable of time from symptom onset to groin puncture (ie, initiation of endovascular therapy), with no more than 6 hours as a predictor of good outcome (OR 1.75; P = 0.017).

Whether or not patients had prior IV tPA made no difference to either functional outcome or mortality.

Encouraging, but Patient Selection Crucial

In a telephone interview with TCTMD, Philip M. Meyers, MD, of Columbia University Medical Center (New York, NY), said, “Stroke registries—especially large ones like this—provide important information about stroke interventions in practice, and the investigators identified benefit to endovascular treatment. I think it gives reason for optimism about the future of endovascular treatment, but without randomized, controlled trial data to demonstrate the benefit, we are still at a disadvantage.”

The study used common forms of brain imaging to identify signs of early infarction before initiating intervention. “Identification of appropriate patients for intervention is still evolving and will be pivotal to the success of endovascular therapy in the future,” Dr. Meyers commented.

He pointed to a recent Cleveland Clinic study (Hussain MS, et al. Stroke. 2014:45:467-472) that selected patients based on mulitimodal imaging. “Using MRI data to discern whether or not somebody already had suffered a permanent injury, [the investigators] reduced the number of people who underwent intervention by half,” Dr. Meyers said. As a result, the patients who did undergo the procedure had better outcomes— and so did the patients who did not undergo the interventional procedure. “This effectively says that endovascular treatment of patients with a completed infarct can make them worse off than no intervention,” he explained.

Such results highlight the possibility that endovascular trials “are contaminated by patients who shouldn’t be enrolled,” he explained. “In the current study, although the investigators ended up with good outcomes, there were probably a number of patients who weren’t likely to respond regardless of the type of therapy they received. That would explain why there are very high rates of vessel recanalization but still only a 43% rate of good functional outcome. This is a fairly common feature of stroke trials, and the small differential between good and bad outcomes can limit the likelihood that randomized trials will show the benefit of endovascular intervention.”

There are obvious limitations to registries, especially the absence of controls, Dr. Meyers observed. Nonetheless, he added, “these are the sort of data that keep us working to try to develop new and better ways to treat ischemic stroke and trials to prove the benefit. I think we have a better understanding now of what that will take, and this registry speaks to some of those issues.”

Registry Represents ‘Iterative Step’ Toward Improved Therapy

In a telephone interview with TCTMD, Adnan H. Siddiqui, MD, PhD, of the University at Buffalo (Buffalo, NY), was upbeat about the registry results. “This is more data to support that intervention has a role to play in these patients,” he said. “It is consistent with our understanding [from IMS III and other trials] that mechanical recanalization for large vessel occlusions is beneficial.”

In particular, the data prove that recanalization, age, and timely treatment all matter, Dr. Siddiqui stated. The negative impact of older age may be related to the tendency of such patients to have more comorbidities and tortuous anatomy, he added, suggesting that a direct cervical rather than transfemoral approach may sidestep the latter problem.

Overall, “this is an iterative step proving that recanalization with new technologies such as stent retrievers—which predominated in the registry—works much better than in previous studies,” he commented. “The big conclusion is that if you recanalize these patients, they have about a 50% chance of a good outcome, and I think that’s fantastic.”

With the next generation of trials, Dr. Siddiqui continued, “we’ve gotten smarter about who to enroll and who not to enroll. They are all looking at anterior circulation occlusions. You need CTA evidence of what is blocked; you cannot rely on NIHSS score alone. I personally believe that perfusion imaging is going to be a big factor.”

Study Details

The mean age was 67.5 years, 54.9% were male, and the median baseline NIHSS score was 17.5. Overall, 87.9% of patients had an anterior circulation occlusion.

Solitaire (Covidien, Plymouth, MN) and Trevo (Stryker, Kalamazoo, MI) stent retrievers were used in more than 85% of cases in 6 of 7 comprehensive stroke centers.

Related Stories:

• Endovascular Therapy Bests IV t-PA for Large-Vessel Strokes
• IMS III: Endovascular Therapy Fails to Improve Stroke Recovery vs. t-PA Alone
• Meta-analysis: Endovascular Therapy Improves Outcomes in Acute Ischemic Stroke