(click for larger image)Additional Inclusion/Exclusion Characteristics of Patients Presenting within Three to 4.5 hours from Symptom Onset for tPA Therapy
The American Heart Association/American Stroke Association (AHA/ASA) guidelines now recommend the use of IV tPA for patients within three hours of onset of ischemic stroke, with treatment initiated as quickly as possible (Class I; Level A). Although it has not been FDA approved, IV tPA treatment of eligible patients within the three to 4.5-hour window is recommended as Class I-Level B evidence with exclusions as in the ECASS study.4 Inclusion and exclusion criteria for tPA according to AHA/ASA guidelines can be found in Table 2.
IA thrombolysis/thrombectomy: Over the last two decades, there has been great interest in endovascular treatment of acute ischemic stroke and large advances in the numbers and types of treatments available. The FDA has approved multiple devices developed for mechanical thrombectomy based on their ability to recanalize vessels; however, to date, there is no clear evidence that thrombectomy improves patient outcomes. Several studies of endovascular therapy were recently published, including the Interventional Management of Stroke III (IMS 3) study, the Mechanical Retrieval and Recanalization of Stroke Clots using Embolectomy (MR RESCUE) study, and the SYNTHESIS Expansion study.8,9,10 None of these studies showed a benefit to endovascular treatment; however, critics have pointed out many flaws in these studies, including protracted time to treatment and patient selection. Furthermore, the most recent devices, like Solitaire and Trevo, were not used in most patients.
Three more recent trials found promising results for interventional treatment.11-13 The trials ranged from 70 to 500 patients with anterior circulation strokes with a large vessel occlusion; each study found a statistically significant improvement in functional independence at three months in the intervention group.12,13 Intravenous tPA was given in 72.7% to 100% of patients.11,12 Intervention to reperfusion was very quick in each study.
Some possible reasons for the more successful outcomes include the high proportion of newer devices for thrombectomy used and rapid treatment of symptoms, with symptom onset to groin puncture medians ranging from 185 minutes to 260 minutes.11,13 It remains clear that careful patient selection should occur, and those who are not candidates for intravenous therapy who present inside an appropriate time window could be considered. Time from symptom onset continues to be an important piece of making decisions about candidates for interventional treatment, but some advocate for the use of advanced imaging modalities, such as DWI imaging on MRI, or MR, or CT perfusion imaging, to help decide who could be a candidate.
Back to the Case
IV tPA was given to the patient 30 minutes after presentation. She met all inclusion and exclusion criteria for treatment and received the best-proven therapy for acute ischemic stroke. Due to her severe symptoms, the neurointerventional team was consulted for possible thrombectomy. This decision is controversial, as there is no proven benefit to intraarterial therapy. She was a possible candidate because of her time to presentation, large vessel occlusion, and substantial penumbra with CT imaging (see Figure 1).
About 20 minutes after treatment, she began to improve, now lifting her left arm and leg against gravity and showing less dysarthria. The decision was made to perform a conventional angiogram to reevaluate her blood vessels and to consider thrombectomy based upon the result. The majority of her middle cerebral artery had recanalized, so no further interventions were needed.
Bottom Line
Intravenous tPA (alteplase) is indicated for patients presenting within 4.5 hours of last known normal. Careful patient selection should occur if additional therapies are considered.