AT ANA 2016
BALTIMORE (FRONTLINE MEDICAL NEWS) – Endovascular therapy is a bedrock of acute ischemic stroke treatment, but some vexing issues remain unresolved, according to Joseph Broderick, MD, of the University of Cincinnati.
“We have learned a tremendous amount the last few years. We know that thrombectomy can work if initiated in patients within 6 hours of stroke onset with or without TPA [tissue plasminogen activator]. The question is what we don’t know,” Dr. Broderick said.
The good news is that clinical trials are underway or planned to address several of these issues, he said at the annual meeting of the American Neurological Association.
Mechanical thrombectomy beyond 6 hours
Whether the treatment window for thrombectomy can be safely extended in appropriately selected patients beyond 6 hours from onset is “one of the most important issues we face,” Dr. Broderick said.
There are indications from several trials that patients with salvageable tissue can respond to reperfusion beyond the 6-hour window. The premise of the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution ( DEFUSE 3 ) multicenter trial involving 476 patients is that salvageable tissue can be identified over a 6-hour period from the onset of acute ischemic stroke (AIS) symptoms using imaging techniques. If this premise bears out in DEFUSE 3, CT and MRI may be used to identify patients who will benefit from endovascular therapies at a prolonged time post AIS.
Along with DEFUSE 3, the DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention ( DAWN ) trial will examine whether medical management that includes thrombectomy delivered up to 24 hours after AIS symptoms first appear will yield better clinical outcomes than medical management alone in appropriate patients.
The use of mechanical thrombectomy up to 12 hours after symptom development in AIS patients for whom intravenous TPA can’t be used or doesn’t work will be assessed in the Perfusion Imaging Selection of Ischemic Stroke Patients for Endovascular Therapy ( POSITIVE ) trial. The primary objective is to show less stroke-related disability and improved good functional outcomes, compared with those who receive best medical therapy.
The first Multicenter Randomized Clinical Trial of Endovascular Treatment in the Netherlands (MR CLEAN) trial, which used stent retrievers in almost all cases, demonstrated the benefit of endovascular therapy up to 6 hours after stroke onset in the proximal anterior circulation when used along with best medical therapy ( N Engl J Med. 2015;372:11-20 ). The MR CLEAN LATE trial involving 500 patients will expand the time window up to 12 hours.
Triage of acute stroke patients
The triage of AIS patients before their arrival at the hospital also is an evolving emergency medical service issue. While the classic triage involving CT takes time, the use of scoring systems like the National Institutes of Health Stroke Scale and the Cincinnati Stroke Triage Assessment Tool, or telemedicine-based consultation, can be done faster and with less training.
Where the patient is taken first could be important. The RACECAT trial being conducted in the Catalan territory will compare transfer of acute stroke patients with suspected large-vessel occlusion to the closest local stroke center versus direct transfer to an endovascular stroke center.
Conscious sedation or general anesthesia
Some patients undergoing thrombectomy may be able to tolerate conscious sedation in place of general anesthesia. For these patients, cost-effectiveness becomes a dominant consideration. Several anesthesia trials are addressing the issue. The Sedation Versus Intubation for Endovascular Stroke Treatment ( SIESTA ) trial involving 150 German patients has been completed, but the findings have not been reported. The General or Local Anaesthesia in Intra-arterial Therapy ( GOLIATH ) trial is recruiting patients in the Netherlands, with a target enrollment of 128. Other trials are planned in China and Sweden, but recruitment has not started.
Thrombectomy alone
For patients with AIS caused by basilar artery occlusion, stroke specialists have wondered whether intra-arterial treatment, including thrombolysis and potentially thrombectomy, could be more effective than best medical therapy, including intravenous thrombolysis. The Basilar Artery International Cooperation Study ( BASICS ) in Europe and the BEST trial in China are two trials in the early stages of assessing this question.
A related issue is whether thrombectomy alone is better than intravenous TPA followed by thrombectomy. This issue is being addressed in another MR CLEAN trial that is designed to compare the two approaches in 500 patients randomized to one or the other treatment.
Other intravenous antithrombotic drugs
Another unresolved issue relates to the use of other antithrombotic medications delivered intravenously in combination with TPA. This could be the sole treatment strategy, or could be used in patients who also undergo endovascular thrombectomy. The Multi-Arm Optimization of Stroke Thrombolysis ( MOST ) trial will randomize patients to receive argatroban or eptifibatide along with TPA, or TPA alone, within 3 hours of stroke symptom onset. Endovascular therapy will be done as indicated.
Heparin use in endovascular therapy
The proper use of antithrombotics like heparin in patients treated with endovascular therapy is unclear. The MR CLEAN MED trial will assess the benefits of two doses of unfractionated heparin and aspirin alone or in combination in 1,500 patients with AIS who receive intra-arterial treatment for confirmed anterior circulation occlusion.
On the horizon
Whether neuroprotection can improve the outcome in patients who undergo embolectomy is unclear, and will be the subject of a trial in Canada that is not yet recruiting patients. Finally, the best way to manage blood pressure following embolectomy and reperfusion is also unclear.
Dr. Broderick had no relevant financial disclosures.
