ENCHANTED Trial: Intensive Blood Pressure Reduction During IV Alteplase Treatment
In patients with acute ischemic stroke eligible for IV alteplase, does intensive SBP lowering (target 130-140 mm Hg for 72 hours) during and after thrombolysis improve 90-day functional outcomes compared with guideline management (SBP below 180 mm Hg)?
Anderson et al. (Lancet 2019) · doi:10.1016/S0140-6736(19)30038-8 · 2196 patients
Population
Included
- Age 18 or older
- Acute ischemic stroke eligible for IV alteplase
- SBP 150 mm Hg or greater at randomization
- Measurable neurological deficit on NIHSS
- Randomization within 6 hours of symptom onset
- Adults aged 18 years or older
- Acute ischaemic stroke fulfilling standard criteria for treatment with intravenous alteplase (treated with alteplase)
- Systolic blood pressure 150 mm Hg or more
- Treating clinician had uncertainty over the benefit and risk of the intensity of blood-pressure control during and for up to 72 h after thrombolytic treatment
- Randomisation within 6 h of stroke onset (the time-to-randomisation window was extended from within 4.5 h to within 6 h by a protocol amendment on Nov 12, 2013)
Excluded
- SBP below 150 mm Hg at presentation
- Contraindication to antihypertensive therapy
- Hemorrhagic stroke on baseline imaging
- Pre-stroke mRS 3 or greater
- Patient unlikely to benefit from thrombolysis (for example, had advanced dementia)
- Very high likelihood of death within 24 h
- Substantial comorbidity that would interfere with the outcome assessments or follow-up (known pre-stroke disability, with estimated modified Rankin Scale score 2 to 5)
- A specific contraindication to alteplase or to any of the blood-pressure-lowering drugs to be used
- Currently participating in another clinical trial of a pharmacological agent
Source: Anderson et al., Lancet 2019;393:877–888 (ENCHANTED blood-pressure arm)· Retrieved 2026-06-09
Primary Outcome — mRS Ordinal Shift at 90 Days
2196 patients; intensive SBP 130-140 mm Hg vs guideline below 180 mm Hg for 72 hours
mRS Ordinal Shift at 90 Days (Primary)
OR 1.01
95% CI 0.87 to 1.17 · P = 0.87
Pre-specified secondary — any ICH at 24 hours: 14.8% (intensive) vs 18.7% (guideline), OR 0.75, P=0.014. Significant reduction in hemorrhage was not accompanied by improvement in the primary functional outcome.
Mortality similar between groups · 110 sites, 15 countries
Study Arms
- Agent
- Locally available intravenous, oral, and topical antihypertensive agents (bolus and infusion)
- Dose
- Target systolic blood pressure 130 to 140 mm Hg, achieved within 1 h of randomisation
- Route
- Per agent (intravenous, oral, or topical)
- Frequency
- Titrated to the systolic target
- Duration
- Maintained for 72 h during and after intravenous alteplase
- Co-interventions
- Intravenous alteplase per local protocol; managed in an acute stroke unit or equivalent monitored environment; endovascular thrombectomy when used in clinical practice was permitted.
Intensive arm, n=1081. A Nov 12, 2013 amendment lowered the intensive target (originally 140 to 150 mm Hg) to 130 to 140 mm Hg to widen the between-group difference. Anderson Lancet 2019 p.879.
- Agent
- Locally available antihypertensive agents per guideline
- Dose
- Target systolic blood pressure less than 180 mm Hg (patients required to comply with thrombolysis guidelines, which require SBP 185 mm Hg or lower before alteplase)
- Route
- Per agent (intravenous, oral, or topical)
- Frequency
- Treated to keep SBP below the 180 mm Hg target
- Duration
- Maintained for 72 h during and after intravenous alteplase
- Co-interventions
- Intravenous alteplase per local protocol; managed in an acute stroke unit or equivalent monitored environment; endovascular thrombectomy when used in clinical practice was permitted.
Guideline arm, n=1115. Anderson Lancet 2019 p.879.
Trial Design
Type
- International randomized open-label trial with blinded endpoint assessment
- Intensive SBP target 130-140 mm Hg vs guideline target <180 mm Hg
- Adults with acute ischemic stroke eligible for IV alteplase
- Blood pressure strategy applied for 72 hours
Timeline
Conducted at 110 sites in 15 countries
N
2196
Enrollment
2196 patients at 110 sites across 15 countries. Open-label trial with blinded endpoint assessment. Intensive SBP target 130-140 mm Hg vs guideline less than 180 mm Hg for 72 hours. Published Lancet 2019.
ClinicalTrials.gov
NCT01422616Bedside Pearl
ENCHANTED showed intensive post-alteplase BP lowering reduced any-ICH as a secondary outcome but did not improve 90-day disability (primary null). Do not use the secondary ICH finding to justify changing post-alteplase BP targets. Current standard (SBP below 180 mm Hg) remains the evidence-based practice.