Therapeutic-Induced Hypertension in Patients with Non-Cardioembolic Acute Stroke: A Multicentre, Randomised Controlled Trial

Abstract

Background: In this multicentre, randomised controlled trial, we evaluated the safety and efficacy of induced hypertension in patients with acute ischaemic stroke. Methods: Patients with acute non-cardioembolic ischaemic stroke within 24 hours of onset who were ineligible for revascularisation 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 intravenously administered to increase systolic blood pressure (SBP) up to 200 mmHg. The primary efficacy endpoint was early neurological improvement (reduction in NIHSS score ≥ 2 points during the first 7 days). The secondary efficacy endpoint was a modified Rankin scale score of 0-2 at 90 days. Safety outcomes included symptomatic intracranial haemorrhage/oedema, myocardial infarction, and death. Findings: Totals of 76 and 77 patients were included in the intervention and control groups, respectively. Relative to the control group, patients in the intervention group were younger, exhibited higher baseline NIHSS values, and were more likely to experience progressive stroke and large vessel occlusion. Sixty-seven (88·2%) patients of the intervention group exhibited improvements in NIHSS scores ≥2 during induced hypertension (mean SBP: 179·7±19·1 mmHg). After adjusting for age and initial stroke severity, induced hypertension increased the occurrence of the primary (odds ratio: 2·49; 95% CI: 1·25-4·96; P=0·010) and secondary efficacy endpoints (odds ratio: 2·97; 95% CI: 1·32-6·68; P=0·009). The numbers needed to treat were 3·7 and 8·4 for the primary and secondary endpoints, respectively. Safety outcomes did not significantly differ between groups. Interpretation: Among patients with non-cardioembolic stroke who were ineligible for revascularisation therapy and those with progressive stroke, phenylephrine-induced hypertension was safe and resulted in early neurological improvement and long-term functional independence (class IB evidence). Clinical Trial Number: This trial is registered with ClinicalTrials.gov (NCT01600235). Funding: Samsung Medical Center and IlDong Pharma, Inc. Seoul, South Korea. Declaration of Interests: All authors declare no competing interests. Ethic Approval Statement: Patients from eight sites in South Korea were enrolled between June 2012 and December 2017. The trial was approved by the appropriate national regulatory authorities and relevant ethnics committee at each participating site. All participants provided written informed consent.