Stroke and Stroke Rehabilitation: Thrombolytic Therapy
Percentage of patients aged 18 years and older with a diagnosis of acute ischemic stroke who arrive at the hospital within 3.5 hours of time last known well and for whom IV thrombolytic therapy was initiated within 4.5 hours of time last known well.
Last updated: January 15, 2026
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📖Clinical Rationale
One trial (ECASS III) specifically evaluating the efficacy of IV alteplase within 3 and 4.5 hours after symptom onset and pooled analysis of multiple trials testing IV alteplase within various time windows support the efficacy of IV alteplase up to 4.5 hours after symptom onset. European Cooperative Acute Stroke Study (ECASS) III excluded octogenarians, patients taking warfarin regardless of international normalized ratio, patients with combined history of diabetes mellitus and previous ischemic stroke, and patients with very severe strokes (National Institutes of Health Stroke Scale [NIHSS] score >25) because of a perceived excessive risk of intracranial hemorrhage in those cases.
However, careful analysis of available published data summarized in an AHA/American Stroke Association (ASA) scientific statement indicates that these exclusion criteria from the trial may not be justified in practice. The Efficacy and Safety of MRI-based Thrombolysis in Wake-Up Stroke (WAKE-UP) random control trial randomized 503 patients with AIS who awoke with stroke or had unclear time of onset and could be treated with IV alteplase within 4.
5 hours of stroke symptom recognition. Eligibility required magnetic resonance imaging (MRI) mismatch between abnormal signal on diffusion-weighted magnetic resonance imaging (DW-MRI) and no visible signal change on fluid-attenuated inversion recovery (FLAIR). DW-MRI lesions larger than one-third of the territory of the middle cerebral artery (MCA), NIHSS score > 25, contraindication to treatment with alteplase, or planned thrombectomy were all exclusions.
Ninety-four percent were wake-up strokes. Median NIHSS score was 6. Median time from last known well to symptom recognition was ≈7 hours and to alteplase administration slightly over 10 hours. The primary end point of a modified Rankin Scale (mRS) score 0 to 1 at 90 days was achieved in 53.3% of the alteplase group and in 41.8% of the placebo group (P=0.
02). Only 20% had large vessel occlusion (LVO) of the intracranial internal carotid or proximal middle cerebral arteries.
📝Clinical Recommendations
IV alteplase (0.9 mg/kg, maximum dose 90 mg over 60 minutes with initial 10% of dose given as bolus over 1 minute) is recommended for selected patients who may be treated within 3 hours of ischemic stroke symptom onset or patient last known well or at baseline state. (Class 1, Level of Evidence: A)(AHA/ASA) (Powers, et al., 2019) It may be reasonable to choose tenecteplase (single IV bolus of 0.
25- mg/kg, maximum 25 mg) over IV alteplase in patients without contraindications for IV fibrinolysis who are also eligible to undergo mechanical thrombectomy (Class IIB, Level of Evidence: B-R) In patients eligible for IV alteplase, because benefit of therapy is time dependent, treatment should be initiated as quickly as possible and not delayed for additional multimodal neuroimaging, such as CT and MRI perfusion imaging.
(Class I, Level of Evidence: B-NR) IV alteplase (0.9 mg/kg, maximum dose 90 mg over 60 minutes with initial 10% of dose given as bolus over 1 minute) is also recommended for selected patients who can be treated within 3 and 4.5 hours of ischemic stroke symptom onset or patient last known well or at baseline state. Physicians should review the criteria outlined in Table 8 to determine patient eligibility.
(Class I, Level of Evidence: B-R) IV alteplase (0.9 mg/kg, maximum dose 90 mg over 60 minutes with initial 10% of dose given as bolus over 1 minute) administered within 4.5 hours of stroke symptom recognition can be beneficial in patients with AIS who awake with stroke symptoms or have unclear time of onset >4.5 hours from last known well or at baseline state and who have a DW-MRI lesion smaller than one-third of the MCA territory and no visible signal change on FLAIR.
(Class IIa, Level of Evidence: B-R) For patients >80 y of age presenting in the 3- to 4.5-h window, IV alteplase is safe and can be as effective as in younger patients. (Class IIa, Level of Evidence: B-NR) For otherwise eligible patients with mild disabling stroke symptoms, IV alteplase may be reasonable for patients who can be treated within 3 and 4.
5 hours of ischemic stroke symptom onset or patient last known well or at baseline state. (Class IIb, Level of Evidence: B-NR) In AIS patients with prior stroke and diabetes mellitus presenting in the 3- to 4.5- h window, IV alteplase may be as effective as treatment in the 0- to 3-h window and may be a reasonable option. (Class IIb, Level of Evidence: B-NR) The benefit of IV alteplase between 3 and 4.
5 h from symptom onset for patients with very severe stroke symptoms (NIHSS score >25) is uncertain.
📋Implementation Notes
This measure contains one strata defined by a single submission criteria. This measure produces a single performance rate. For the purposes of MIPS implementation, this episode measure is submitted once for each occurrence of a particular illness or condition during the performance period.
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