Ninety days after stent retriever therapy with the Solitaire device for acute ischemic stroke, functional independence was equally likely between those who got additional tPA infusion and those who did not (modified Rankin Scale scores of 0-2 observed for 57.7% versus 47.7%, adjusted OR 1.48, 95% CI 0.80-2.74), Vitor M. Pereira, MD, MSc, of Toronto Western Hospital in Canada, and colleagues reported online in JAMA Neurology.
Mortality rates at 90 days were also similar, at 8.1% for the tPA arm and 12.2% for the thrombectomy-alone group (adjusted OR 0.90, 95% CI 0.35-2.30).
"The results indicate that treatment of patients experiencing acute ischemic stroke due to a large vessel occlusion with intravenous thrombolysis before mechanical thrombectomy does not appear to provide a clinical benefit over mechanical thrombectomy alone," Pereira's group concluded, calling for a randomized clinical trial to settle the matter.
"Given that 85% of the patients in mechanical thrombectomy trials received intravenous thrombolysis, [the authors] highlight an important group of patients in whom mechanical thrombectomy was successful without intravenous thrombolysis," commented Gursant S. Atwal, MD, of the University at Buffalo in New York, and Adnan H. Siddiqui, MD, PhD, of Gates Vascular Institute at Kaleida Health, also in Buffalo, writing in an accompanying editorial.
Although there are hypothetical benefits to tPA usage -- such as increased recanalization and thrombolysis of smaller clot fragments -- Atwal and Siddiqui said that there also remain concerns about the possibility of intracranial hemorrhage and over-fragmentation of the clot. What's more, intravenous thrombolysis may reduce the effectiveness of mechanical thrombectomy itself.
For now, the editorial said, "the current study provides the largest independent core laboratory with a clinical endpoint committee -- or a data and safety monitoring board-adjudicated prospective, multicenter data set that ... provides critical data that can be used to design a definitive randomized clinical trial."
There were 291 patients pooled in the analysis by Pereira and colleagues of the Solitaire With the Intention for Thrombectomy (SWIFT) trial and the single-arm Solitaire Flow Restoration Thrombectomy for Acute Revascularization (STAR) study. The investigators had excluded the 55 patients from SWIFT who got the Merci device in lieu of the Solitaire.
At baseline, median Alberta Stroke Program Early CT Scores were lower among tPA recipients (8 versus 9, P=0.04). This group was also less likely to have had a history of atrial fibrillation (33.1% versus 47.3%, P=0.02).
Even so, the rates of procedural characteristics and complications were largely similar between the groups:
- Time from symptom onset to groin puncture (254 minutes for additional tPA versus 262 minutes for thrombectomy alone, P=0.10)
- Number of passes (median of one for both groups, P=0.30)
- Odds of successful reperfusion (84.1% versus 84.7%, P>0.99)
- Emboli traveling to uninvolved territory (4.5% versus 2.4%, P=0.52)
- Symptomatic intracranial hemorrhage (1.3% versus 3.8%, P=0.25)
- Parenchymal hemorrhages type 1 (0.6% versus 3.1%, P=0.18)
- Parenchymal hemorrhages type 2 (0.6% versus 1.5%, P=0.59)
"Strengths of our study include the large sample size, completeness of the data, and the use of independent adjudication committees," the researchers wrote.
"Several limitations also warrant comment. First, patients were not randomized for the use of intravenous thrombolysis. Patients who underwent mechanical thrombectomy alone usually had a contraindication for intravenous thrombolysis that may have affected their outcomes. We adjusted for baseline imbalances in the multivariate analyses, but still we cannot exclude the possibility of residual confounders."
Additionally, they acknowledged, "the finding that intravenous thrombolysis was associated with a lower risk of intracranial hemorrhage, a somewhat counterintuitive observation, should especially be interpreted with caution, given the low number of patients with a symptomatic intracranial hemorrhage in either group."
The authors also noted that not all tPA recipients received the same dose.
Pereira disclosed consulting for the SWIFT and/or STAR studies.
Siddiqui reported financial relationships with Buffalo Technology Partners, Cardinal, International Medical Distribution Partners, Medina Medical Systems, Neurotechnology Investors, StimSox, and Valor Medical, Amnis Therapeutics, Cerebrotech Medical Systems Inc., CereVasc, Codman, Corindus, Covidien, GuidePoint Global Consulting, Lazarus, Medtronic, MicroVention, Neuravi, Penumbra, Pulsar Vascular, Rapid Medical, Rebound Medical, Reverse Medical, Silk Road Medical, Stryker, The Stroke Project, Three Rivers Medical, and W. L. Gore & Associates; as well as being a principal investigator or serving on the national steering committee for related studies and trials; and being a member of the board of the Intersocietal Accreditation Committee.
Atwal reported no relevant relationships with industry.
- Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner