Another Meta-analysis Strengthens Case for Endovascular Therapy in Acute Stroke

For the second time in a month, a meta-analysis of randomized trial data has confirmed that patients with acute stroke who undergo mechanical thrombectomy after administration of thrombolysis have better functional outcomes than those given thrombolysis alone. The study, published in the December 08, 2015, issue of the Journal of the American College of Cardiology, also found a trend toward reduced mortality with the combination therapy. 

“These studies will likely expand the clinical use of thrombectomy for acute ischemic stroke,” said Anthony A. Bavry, MD, MPH, of North Florida/South Georgia Veterans Health System (Gainesville, FL), in an email with TCTMD.

Bavry and colleagues conducted the meta-analysis of 9 trials published between 2013 and 2015, all of which compared mechanical thrombectomy after usual care (mostly IV thrombolysis) vs usual care alone for acute ischemic stroke.

The trials were: MR RESCUE, IMS III, MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT, THERAPY, and THRACE. Studies that did not permit thrombolysis before mechanical thrombectomy, such as SYNTHESIS Expansion, were not included. Use of retrievable stents was mandated in 3 trials (EXTEND-IA, SWIFT PRIME, REVASCAT), encouraged in 2 (ESCAPE, MR CLEAN) and allowed in 2 others (IMS III, MR RESCUE).

Functional Outcomes Greatly Improved

Overall, data on 2,410 patients were analyzed. Compared with those who received thrombolysis (primarily tPA) alone, patients who also were treated with mechanical thrombectomy had a greater likelihood of achieving good functional outcome, defined as modified Rankin scale (mRS) score of 0 to 2 at 90 days (primary outcome). Thrombectomy patients also were more likely to have excellent functional outcome, defined as mRS score of 0 to 1 (secondary outcome), with a trend toward reduced all-cause mortality. There was no difference between treatment groups with regard to risk of symptomatic intracranial hemorrhage.

Findings for the primary outcome and for mortality were similar after excluding trials that allowed intra-arterial thrombolysis (MR RESCUE, IMS III, and MR CLEAN).

Meta-regression analysis demonstrated improved outcomes for more recent trials of stent retrievers, but it found no difference in treatment effect based on time to mechanical thrombectomy.

Thrombectomy also showed an advantage for recanalization. Among trials reporting that endpoint, mechanical thrombectomy improved recanalization compared with thrombolysis alone (RR 1.57; 95% CI 1.11-2.23).

Additionally, the thrombectomy group had a nonsignificantly higher risk of recurrent stroke at 90 days compared with usual care (P = .24), driven mainly by the greater embolic stroke rate seen in MR CLEAN (5.6% vs 0.4%). Excluding that trial resulted in a similar risk of recurrent stroke for both groups (P = .77).

Future Considerations

Despite the good outcomes for mechanical thrombectomy, Bavry and colleagues note that the procedure needs to be performed at specialized centers and “therefore, the widespread application of this therapy for acute ischemic stroke patients will likely remain limited for the foreseeable future.” One recent study from the Get With The Guidelines-Stroke registry reported that fewer than half (41.8%) of “participating hospitals were capable of providing endovascular therapy for acute stroke,” the paper points out.

Bavry said it will probably take a year or longer to know if the positive results of the recent trials and the meta-analyses have increased thrombectomy use for acute ischemic stroke “as existing stroke centers increase their efficiency and new stroke centers come online.”

In an accompanying editorial, Gregory W. Albers, MD, of Stanford Stroke Center (Palo Alto, CA), and Jonathan L. Halperin, MD, of Mount Sinai Medical Center (New York, NY), mull over the question of why mechanical thrombectomy appears to work so well in stroke patients and yet has failed as an adjunctive therapy in the treatment of STEMI. Recent trials such as TOTAL and TASTE found no evidence of benefit when manual aspiration thrombectomy was used prior to primary PCI. It is unclear, they say, whether the difference is related to ways in which myocardial microcirculation are differentially affected by interventional technologies, or whether similar processes are at work in the brain. 

“There is much debate why thrombectomy is not effective in STEMI and may even increase the risk of stroke,” Bavry noted. One possible explanation for the differences, he said, is that STEMI is usually due to plaque rupture and variable amounts of intraluminal thrombus, while acute stroke is usually due to embolization and large thrombus burden.

“Thus, a larger proportion of acute stroke patients may derive benefit from thrombectomy,” he said. “Also, current aspiration thrombectomy devices, which are used in STEMI, are not 100% effective at removing thrombus.”

Sources: 
1. Elgendy IY, Kumbhani DJ, Mahmoud A, et al. Mechanical thrombectomy for acute ischemic stroke: a meta-analysis of randomized trials. J Am Coll Cardiol. 2015:Epub ahead of print.
2. Albers GW, Halperin JL. Standards and barriers in acute stroke therapy: a leap forward in the evolution of endovascular interventions for stroke [editorial]. J Am Coll Cardiol. 2015:Epub ahead of print. 

Disclosures:

• Bavry reports having received honoraria from the American College of Cardiology.  
• Halperin reports serving as a consultant to Boston Scientific, Johnson & Johnson, and Medtronic.  
• Albers reports having an equity interest in iSchemaView and serving as a consultant to iSchemaView and Medtronic. 

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