Comparative effects of intensive-versus standard-BP lowering treatment in patients with severe ischemic stroke in the ENCHANTED trial

Objective: Limited data exist on the optimum level of systolic blood pressure (BP) in thrombolyzed patients with acute ischemic stroke (AIS). We aimed to determine the effects of intensive BP lowering, specifically in patients with severe AIS who participated in the international, Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: Pre-specificed subgroup analyzes of the BP arm of ENCHANTED, a multicenter, partial-factorial, open, blinded outcome assessed trial, in which 2227 thrombolysis-eligible and treated AIS patients with elevated systolic BP (>150 mmHg) were randomized to intensive (target 130-140 mmHg) or guideline-recommended (10) baseline neurological scores on the National Institutes of Health Stroke Scale (NIHSS). The primary efficacy outcome was death or any disability (modified Rankin scale [mRS] scores 2-6). The key safety outcome was intracranial hemorrhage (ICH). Treatment effects estimated in logistic regression models are reported as odds ratios with 95% confidence intervals (CIs). Results: There were 1,311 patients (mean age 67 years; 37% female; median baseline NIHSS of 11 [range 6.0-15.0]) with severe AIS. Overall, there was no significant difference in the primary outcome of death or disability. However, intensive BP lowering significantly increased mortality (odds ratio 1.52, 95% CI 1.09-2.13; P=0.014) compared to guideline BP lowering, despite significantly lowering clinician-reported ICH (odds ratio 0.63, 95% CI 0.43-0.92; P=0.016). Conclusion: Intensive BP lowering is associated with increased mortality in patients with severe AIS despite lowering the risk of ICH. Further randomized trials are required to provide reliable evidence over the optimum systolic BP target in the most serious type of AIS. Trial Registration: ClinicalTrials.gov Identifier: NCT0142261