This study published in Lancet is an international, partial-factorial, open-label, blinded-endpoint trial where researchers assessed intensive blood pressure lowering vs guideline-recommended blood pressure lowering in patients treated with alteplase for acute ischemic stroke.

Anderson CS, et al. - In an international, partial-factorial, open-label, blinded-endpoint trial of thrombolysis-eligible patients (age ≥18 years) with acute ischemic stroke and systolic blood pressure 150 mm Hg or more, researchers assessed intensive blood pressure lowering vs guideline-recommended blood pressure lowering in patients treated with alteplase for acute ischemic stroke. Outcomes suggest intensive blood pressure lowering is safe, however no improvement in clinical outcome was noted with the observed reduction in intracranial hemorrhage vs guideline treatment. These results seemed not supporting a major shift towards this treatment being applied in those receiving alteplase for mild-to-moderate acute ischemic stroke.

Methods

• Patients screened at 110 sites in 15 countries were enrolled.
• Researchers randomly assigned eligible patients (1:1, by means of a central, web-based program) within 6 hours of onset of stroke to receive intensive (target systolic blood pressure 130–140 mm Hg within 1 hour) or guideline (target systolic blood pressure <180 mm Hg) blood pressure lowering treatment over 72 hours.
• Functional status at 90 days measured by shift in modified Rankin scale scores, analyzed with unadjusted ordinal logistic regression, was assessed as the primary outcome.
• Any intracranial hemorrhage was the key safety outcome.
• They assessed primary and safety outcome in a blinded manner.
• They performed intention-to-treat analyses.

Results

• Researchers randomly allocated 2,227 patients to treatment groups between March 3, 2012 and April 30, 2018.
• Because of missing consent or mistaken or duplicate randomization, they excluded 31 patients; 2,196 alteplase-eligible patients with acute ischemic stroke were thus included: 1,081 in the intensive group and 1,115 in the guideline group, with 1,466 (67.4%) administered a standard dose among the 2,175 actually given intravenous alteplase.
• From stroke onset to randomization, median time interval of 3.3 hours (IQR 2.6–4.1) was observed.
• Over 24 hours, they noted mean systolic blood pressure of 144.3 mm Hg (SD 10.2) in the intensive group and 149.8 mm Hg (12.0) in the guideline group (p < 0.0001).
• The groups did not differ regarding the functional status (mRS score distribution) at 90 days (unadjusted odds ratio [OR] 1.01, 95% CI 0.87–1.17, p=0.8702).
• Intracranial hemorrhage was less frequently evident in the intensive group (160 [14.8%] of 1081) than in the guideline group (209 [18.7%] of 1,115) (OR 0.75, 0.60–0.94, p=0.0137).
• No significant differences were evident in the number of patients with any serious adverse event between the intensive group (210 [19.4%] of 1,081) and the guideline group (245 [22.0%] of 1,115; OR 0.86, 0.70–1.05, p=0.1412).
• No evidence of an interaction of intensive blood pressure lowering with dose (low vs standard) of alteplase with regard to the primary outcome was observed.