Acute Ischemic Stroke Guidelines Highlight Additional Evidence that Stroke Systems of Care Improve Outcomes

Disclosure: Drs. Andino and Birnbaum have nothing to disclose.
Pub Date: Thursday, January 31, 2013
Author: Julio Andino, MD, and Lee Birnbaum, MD
Affiliation: University of Texas Health Science Center

Jauch EC, Saver JL, Adams HP Jr, Bruno A, Connors JJ, Demaerschalk BM, Khatri P, McMullan PW Jr, Qureshi AI, Rosenfield K, Scott PA, Summers DR, Wang DZ, Wintermark M, Yonas H; on behalf of the American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Peripheral Vascular Disease Council, and Council on Clinical Cardiology. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013: published online before print January 31, 2013, 10.1161/STR.0b013e318284056a.

The updated guidelines for the Early Management of Patients with Acute Ischemic Stroke are a comprehensive review of evidence-based stroke care. The revised and new recommendations support aggressive treatment of acute stroke with intravenous (IV) tPA. There is mounting evidence that patients benefit from the development of stroke systems of care which includes coordination between EMS, Acute Stroke Ready Hospitals, Primary Stroke Centers (PSCs), and Comprehensive Stroke Centers (CSCs). The addition of telemedicine or “telestroke” has further expanded the radius of stroke care delivery, as well as improved efficiencies within spoke and hub models. The outcome profiles of telestroke hospitals without an on-site neurologist are similar to that of PSCs.(1) Because stroke patients treated at centers with dedicated stroke resources have better outcomes, the guidelines recommend EMS bypass of hospitals that do not have resources to treat acute stroke. Pre-hospital notification by EMS is also highlighted. The possible benefit of bypassing PSCs for CSCs in selected stroke patients with high NIH Stroke Scales and probable large vessel occlusions was not addressed. This strategy has become more viable since the 2011 ASA publication “Metrics for Measuring Quality of Care in Comprehensive Stroke Centers” (2) and will be further considered if intra-arterial (IA) therapies are clinically proven to improve outcomes.

The guidelines reiterate that only a limited number of laboratory and radiographic tests are required before administering IV tPA. For the majority of eligible patients, only a blood glucose check and a non-contrast enhanced CT (NECT) or MRI are required.  Although baseline ECG, troponin, and CXR are recommended, these tests should not delay IV tPA administration. In the absence of additional cardiopulmonary symptoms, the utility of these additional tests are questionable, especially when considering their potential for delaying treatment. Another delay may result from the addition of advanced neuroimaging (CTA/CTP/MRI) in the initial stroke assessment. The NECT remains the most practical initial imaging modality for efficient IV tPA triage. The guidelines strongly recommend additional advanced neuroimaging for potential IA thrombectomy patients with the caveat that obtaining such advanced neuroimaging does not delay IV thrombolysis. Delays may occur due to extended time in the scanner or IV issues such as contrast infiltration. In general, advanced neuroimaging is best obtained after initiating IV tPA infusion. This strategy favors the time interval from door to tPA bolus to be 60 minutes or less and maximizes the time dependent benefits of IV tPA.

The guidelines also address the potential exclusion criteria of early ischemic changes on initial head CT. The presence of frank hypodensity or edema on NECT is associated with an increased risk of symptomatic ICH after IV tPA administration. However, patients with subtle early ischemic changes on NECT, such as loss of gray-white differentiation, do not have an increased risk and generally, show benefit from IV tPA.(3) The predictive utility of identifying these subtle changes is further clouded by poor reader reliability. Thus, the guidelines recommend IV fibrinolytic therapy “in the setting of early ischemic changes (other than frank hypodensity) on CT, regardless of their extent”.

IA mechanical thrombectomy has emerged as a promising therapy for a subset of stroke patients that are often identified with advanced neuroimaging. Though the recent FDA approval of stentrievers has added excitement, the use of IA therapies has been tempered by the early termination of the phase III Interventional Management of Stroke III trial. Although the trial was stopped early due to futility, there were no safety concerns with the IA therapy arm. These results suggest that time of ictus alone does not adequately identify patients that might benefit from IA therapies.  A combination of variables such as time, advanced neuroimaging, age, or glucose may be more predictive of outcomes. The guidelines acknowledge that IA thrombectomy devices improve recanalization rates but additional randomized controlled trials are needed to establish improved clinical outcomes.

The recommendations provide guidance for the management of patients on the newer anticoagulants in the setting of acute stroke. Both dabigatran and rivaroxaban have been FDA approved for non-valvular atrial fibrillation, but readily available ED tests for levels have yet to be established.  Dabigatran shows linear correlation with thrombin time and ecarin clotting time. Rivaroxaban requires a direct factor Xa inhibitor activity assay. Until reliable, simple tests are available, the recommendation is to rely on medical history to determine when the patient last took these medicines. IV tPA administration seems reasonable for eligible patients who have not received these medicines for at least 2 days.  The utility of these newer anticoagulants as an adjunct to IV tPA in acute stroke management is being studied. The most recent factor Xa inhibitor to be approved by the FDA is apixiban. 

The guidelines address the lack of clinical evidence for the use of devices to augment cerebral blood flow, drug-induced hypertension, or volume expansion in the treatment of acute stroke. The use of albumin has shown promise, but the phase III Albumin in Acute Stroke Part 2 (ALIAS2) Trial was recently stopped prematurely by the study DSMB. In addition, neuroprotective pharmacologic agents, including statins and magnesium, and hypothermia have yet to definitively demonstrate improved outcomes in clinical stroke trials. Although recommended by the AHA in comatose patients post cardiac arrest, hypothermia has not been clinically proven to improve outcomes in acute stroke patients. To date, more than 100 clinical trials on neuroprotective treatments for acute stroke have yet to yield a proven therapy. Future studies may be more fruitful by following the STAIR criteria and starting treatment earlier. Neuroprotective agents appear unlikely to show benefit when given beyond six hours from stroke onset.

In summary, the updated clinical evidence in the guidelines has been insufficient to make Class I recommendations about emerging IA and neuroprotective therapies. However, sufficient evidence exists to recommend the continued development of coordinated stroke systems of care that incorporate stroke care quality improvement processes. The identification and correction of stroke care quality deficiencies improves outcomes and sets the stage for effective implementation of emerging acute stroke therapies.

1. 1. Sairanen T, Soinila S, Nikkanen M, Rantanen K, Mustanoja S, Farkkila M, Pieninkeroinen I, Numminen H, Baumann P, Valpas J, Kuha T, Kaste M, Tatlisumak T. Two years of Finnish Telestroke: thrombolysis at spokes equal to that at the hub. Neurology. 2011;76:1145-1152.
2. 2. Leifer D, Bravata DM, Connors JJ, 3rd, Hinchey JA, Jauch EC, Johnston SC, Latchaw R, Likosky W, Ogilvy C, Qureshi AI, Summers D, Sung GY, Williams LS, Zorowitz R. Metrics for measuring quality of care in comprehensive stroke centers: detailed follow-up to Brain Attack Coalition comprehensive stroke center recommendations: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42:849-877.
3. 3. Patel SC, Levine SR, Tilley BC, Grotta JC, Lu M, Frankel M, Haley EC, Jr., Brott TG, Broderick JP, Horowitz S, Lyden PD, Lewandowski CA, Marler JR, Welch KM. Lack of clinical significance of early ischemic changes on computed tomography in acute stroke. Jama. 2001;286:2830-2838.

-- The opinions expressed in this commentary are not necessarily those of the editors or of the American Heart Association --