Therapeutic-induced hypertension in patients with noncardioembolic acute stroke

Abstract

Objective: To evaluate the safety and efficacy of induced hypertension in patients with acute ischemic stroke.

Methods: In this multicenter randomized clinical trial, patients with acute noncardioembolic ischemic stroke within 24 hours of onset who were ineligible for revascularization therapy and those with progressive stroke during hospitalization were randomly assigned (1:1) to the control and intervention groups. In the intervention group, phenylephrine was administered intravenously to increase systolic blood pressure (SBP) up to 200 mm Hg. The primary efficacy endpoint was early neurologic improvement (reduction in NIH Stroke Scale [NIHSS] score of ≥2 points during the first 7 days). The secondary efficacy endpoint was a modified Rankin Scale score of 0 to 2 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage/edema, myocardial infarction, and death.

Results: In the modified intention-to-treat analyses, 76 and 77 patients were included in the intervention and control groups, respectively. After adjustment for age and initial stroke severity, induced hypertension increased the occurrence of the primary (odds ratio 2.49, 95% confidence interval [CI] 1.25-4.96, p = 0.010) and secondary (odds ratio 2.97, 95% CI 1.32-6.68, p = 0.009) efficacy endpoints. Sixty-seven (88.2%) patients of the intervention group exhibited improvements in NIHSS scores of ≥2 points during induced hypertension (mean SBP 179·7 ± 19.1 mm Hg). Safety outcomes did not significantly differ between groups.

Conclusion: Among patients with noncardioembolic stroke who were ineligible for revascularization therapy and those with progressive stroke, phenylephrine-induced hypertension was safe and resulted in early neurologic improvement and long-term functional independence.

Clinicaltrialsgov identifier: NCT01600235.

Classification of evidence: This study provides Class III evidence that for patients with acute ischemic stroke, therapeutic-induced hypertension increases the probability of early neurologic improvement.

© 2019 American Academy of Neurology.

Figures

Figure 1. Schematic overview of the protocol for the SETIN-HYPERTENSION trial

DWI = diffusion-weighted imaging; FAST-Coll = fast analysis system for collaterals; IQR = interquartile range; mRS = modified Rankin Scale; NIHSS = NIH Stroke Scale; PE = phenylephrine; PWI = perfusion-weighted imaging; SBP = systolic blood pressure; SETIN-HYPERTENSION = Safety and Efficacy of Therapeutic Induced Hypertension in Acute Non-Cardioembolic Ischemic Stroke.

Figure 2. Study flow

Figure 3. Early neurologic outcomes at day 7 and functional outcomes at day 90

(A) NIH Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) score.

Figure 4. Subgroup analyses

CI = confidence interval; EVT = endovascular treatment; IVT = IV thrombolysis; LAA = large artery atherosclerosis; OR = odds ratio; SAO = small artery occlusion; SBP = systolic blood pressure.

Figure 5. Systolic blood pressure (SBP) over time in each group