Bang OY, Chung JW, Kim SK, et al. Therapeutic-induced hypertension in patients with noncardioembolic acute stroke. Neurology. 2019 Nov 19;93(21):e1955-e1963. doi: 10.1212/WNL.0000000000008520. Epub 2019 Oct 23.

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.


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.

Ratings by Clinicians (at least 3 per Specialty)
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Comments from MORE raters

Internal Medicine rater

This is an interesting study that demonstrates that induced hypertension may be beneficial in a small subset of stroke patients. This is not a definite finding, however, because there was a lack of blinding and only about 3% of those who were screened were randomized. This study does provide the basis for a larger trial.

Internal Medicine rater

That hypotension in acute stroke can worsen outcomes is well known. Whether therapeutic hypertension can improve outcomes is currently not known. In this double-blind study, patients with non-cardioembolic stroke who were not candidates for tPA were randomized to phenylephrine to increase blood pressure by 20% for 5 days. For reasons unclear to me, only 4% of the assessed patients made it into the trial. Although their primary endpoint was clearly met (drop in 2 NIHSS points seen in 57% in intervention and 31% in control), it was interesting that 90-day modified Rankin score for disability was not different. They note no difference in major safety outcomes, however, there was 1 symptomatic and 5 asymptomatic ICHs in the intervention group (0 in control). Given the study was done in a Korean population (higher intercerebral stenoses) and given safety concerns, I do not believe this is ready for prime time until repeated in other populations and ICH rates are studied.

Neurology rater

The study is underpowered and the primary outcome of a change of 2 NIHSS points is not clinically relevant. This pilot study requires the next phase 3 trial.

Neurology rater

This RCT assessed induced hypertension in acute ischemic stroke patients who were ineligible for reperfusion therapy. Although they enrolled a small specific subset of patients, both the early improvement after rise in BP and 3-month functional outcomes suggest benefit of protocolized-induced hypertension. Baseline imbalances between the groups and open-label design are significant limitations to the reliability of the study results.