Enhanced Control of Hypertension and Thrombolysis Stroke Study - ENCHANTED
The goal of the trial was to compare the safety and efficacy of low-dose alteplase compared with standard-dose alteplase in the treatment of patients with acute ischemic stroke.
Contribution to the Literature: The ENCHANTED trial showed that low-dose alteplase did not meet criteria for noninferiority of death or major disability compared with standard-dose alteplase in patients with acute ischemic stroke, but intracerebral hemorrhage was significantly lower with the low-dose protocol.
Patients with acute ischemic stroke were randomized in an open-label fashion to either low-dose alteplase (0.6 mg/kg; 15% as bolus, rest as infusion over 60 minutes; maximum dose 60 mg) (n = 1,654) or standard dose alteplase (0.9 mg/kg; 10% bolus, rest as infusion over 60 minutes, maximum dose 90 mg) (n = 1,643).
- Total number of enrollees: 3,310
- Duration of follow-up: 90 days
- Mean patient age: 67.5 years
- Percentage female: 38%
- Acute ischemic stroke eligible for thrombolytic therapy administration
- Drug commenced within 4.5 hours of stroke onset
- Unlikely to benefit from the therapy due to pre-existing disability (e.g., advanced dementia) or very high likelihood of death within 24 hours
- Had another medical illness that interfered with outcome assessments
Other salient features/characteristics:
- Asian race: 63%
- Prior stroke: 18%
- National Institutes of Health Stroke Scale (NIHSS) score: 8
- Proximal vessel occlusion on computed tomography angiography or magnetic resonance angiography: 15.5%
- Median stroke-to-needle time: 170 minutes
The primary outcome, combined mortality or disability defined by scores of 2-6 on modified Rankin scale (mRS) for low-dose vs. standard-dose alteplase, was 53.2% vs. 51.1%, respectively (odds ratio 1.09, 95% confidence interval 0.95-1.25; p for noninferiority = 0.51). Death within 90 days was 8.5% vs. 10.3% for low-dose vs. standard-dose alteplase, respectively (p = 0.07).
- Symptomatic intracerebral hemorrhage (National Institute of Neurological Disorders and Stroke [NINDS] criteria): 5.9% vs. 8.0%, p = 0.02
- Fatal cerebral hemorrhage: 1.3% vs. 2.5%, p = 0.02
The results of this trial indicate that low-dose alteplase did not meet criteria for noninferiority of death or major disability compared with standard-dose alteplase in patients with acute ischemic stroke receiving thrombolytic therapy within the 4.5-hour window. However, intracerebral hemorrhage was significantly lower with the low-dose protocol, irrespective of the definition employed. This suggests that patients surviving with low-dose alteplase compared with standard-dose alteplase were more likely to have important residual neurological disabilities. It is unclear if there are certain subgroups (such as those already on antiplatelet agents) where the low-dose protocol might be beneficial.
Anderson CS, Robinson T, Lindley RI, et al., on behalf of the ENCHANTED Investigators and Coordinators. Low-Dose Versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke. N Engl J Med 2016;May 10:[Epub ahead of print].
Editorial: Sila C. Finding the Right t-PA Dose for Asians With Acute Ischemic Stroke. N Engl J Med 2016;May 10:[Epub ahead of print].
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