Although intensive blood pressure (BP) lowering may reduce risk for intracerebral haemorrhage (ICH) after thrombolytic treatment for acute ischemic stroke (AIS), the protocol does not improve post-stroke recovery, new research suggests.
In the international, open-label Enhanced Control of Hypertension and Thrombolysis Stroke (ENCHANTED) trial, investigators enrolled more than 2000 patients (74% recruited in Asia) and randomly assigned them to one of two BP management groups within 6 hours of stroke onset.
Improvement in functional status at 90 days, as measured by modified Rankin Scale (mRS) scores, did not differ between the group assigned to intensive systolic BP (SBP) lowering targeted to 130 to 140 mmHg within 1 hour and those assigned to a standard, guideline-recommended target of less than 180 mmHg over 72 hours. This meant the trial did not meet its primary efficacy outcome.
The key secondary safety outcome was any reported intracranial haemorrhage; the rate of such haemorrhages was significantly less in the intensive group (14.8% vs 18.7%, respectively).
“This study clearly shows intensive blood pressure lowering has the potential to make thrombolysis treatment safer by reducing risk of serious bleeding in the brain,” primary investigator Craig Anderson, MD, PhD, professor of neurology at the University of New South Wales, Sydney, Australia, who is the executive director of the George Institute China, in Beijing, said in a press release. But he noted that more research is needed to determine why this reduced risk did not translate into improved overall outcome.
“The primary result was neutral, which was a little disappointing because it tells you that you haven’t got an overall improved recovery; but it also tells you that it’s safe because it didn’t make the patients worse,” Anderson told Medscape Medical News.
Findings from the blood-pressure intensity arm of ENCHANTED were presented at a late-breaking science session in Honolulu last week at the International Stroke Conference (ISC) 2019 and were simultaneously published online in the Lancet.
Results showed that the mean SBP over 24 hours was 144.3 mmHg for the intensive group vs 149.8 mmHG for the standard group. Although this resulted in a statistically significant difference (P < .0001), it did not reach the planned 15 mmHg difference.
There was no significant between-group difference in improved mRS scores (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.87 – 1.17; P = .87).
The investigators also assessed “a number of prespecified subgroups. There was no significant heterogeneity in the primary endpoint with respect to age, ethnicity, baseline systolic blood pressure, ischemic stroke subtype, and dose,” co–senior author Thompson G. Robinson, MD, National Institute of Health Research Leicester Biomedical Research Center, the Glenfield Hospital, United Kingdom, told meeting attendees.
However, there were significantly fewer cases of any intracranial haemorrhage in the intensive group (OR, 0.75; 95% CI, 0.60 – 0.94; P = .014). There were also significantly fewer reports of intracranial haemorrhage as a serious adverse event, including major ICH, in the intensive group (5.5% vs 9.0%; OR, 0.59; P = .002).
“There was a clear signal that it reduced bleeding. That’s the most worrying thing about giving thrombolysis, and it’s one of the big barriers that has prevented us from rolling out thrombolysis because of the clear harms of treatment,” Anderson said.
There were no significant differences in other efficacy and safety outcomes, including death and neurologic decline.
Overall, intensive BP lowering “was not shown to be superior to guideline-recommended BP lowering for primary disability outcome, and there was a consistency of neutral findings in all prespecified subgroups,” Robinson summarized. The protocol did show, however, that it was safe with respect to mRS scores, serious adverse event reports, and lowered risk for intracranial haemorrhage, he added.
Robinson noted several possible reasons why intensive BP lowering didn’t improve the primary outcome. These included the fact that there were “challenges” with the protocol used for the intensive group; that there was only a small difference in SBP between the groups; that there were few serious ICHs; and that there may have been some bias, owing to the study’s open-label design.
REFERENCE: Anderson et al: Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED): an international, randomised, open-label, blinded-endpoint, phase 3 trial; https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)30038-8/fulltext