BASEL, Switzerland — Early reduction of blood pressure has a beneficial effect in hemorrhagic stroke but a detrimental effect in ischemic stroke, new trial data show. The findings could shake up recommendations on control of blood pressure in acute stroke patients.
“This is the first time that we have randomized evidence of blood pressure control prior to reperfusion in ischemic stroke patients, and our data will challenge the current guidelines that recommend lowering blood pressure to below 180 mm Hg systolic in these patients,” study co-author Craig Anderson, MD, George Institute for Global Health, Sydney, Australia, told Medscape Medical News.
“And this study also clearly shows for the first time that getting blood pressure under control in hemorrhagic stroke patients in the first couple of hours has definitive benefits,” he added.
The findings were presented on May 16 at the European Stroke Organization Conference (ESOC) Annual Meeting and published online simultaneously in The New England Journal of Medicine.
A Test of Early BP Control
The trial was conducted to test the strategy of very early blood pressure control during patient transport in an ambulance after acute stroke, which investigators suspected could benefit patients with both types of stroke.
The hypothesis was that this would reduce bleeding in the brain for those with hemorrhagic stroke. For ischemic stroke patients, it was thought this strategy would speed up administration of thrombolysis, because guidelines recommend bringing blood pressure under control before thrombolysis.
For the INTERACT4 trial, which was conducted in China, 2404 patients with suspected acute stroke and elevated systolic blood pressure (≥ 150 mm Hg) who were assessed in the ambulance within 2 hours after symptom onset were randomized to receive immediate treatment with intravenous urapidil to lower the systolic blood pressure or usual blood pressure management (usual care group).
The median time between symptom onset and randomization was 61 minutes, and the mean blood pressure at randomization was 178/98 mm Hg.
Stroke was subsequently confirmed by imaging in 2240 patients, of whom 46% had a hemorrhagic stroke and 54% an ischemic stroke.
At the time of arrival at the hospital, the mean systolic blood pressure in the intervention group was 158 mm Hg, compared with 170 mm Hg in the usual care group.
The primary efficacy outcome was functional status as assessed by modified Rankin scale score at 90 days.
Overall, there was no difference between the two groups in terms of functional outcome scores (common odds ratio [OR], 1.00; 95% CI, 0.87-1.15), and the incidence of serious adverse events was similar.
But the study showed very different results in patients with hemorrhagic stroke vs those with ischemic stroke.
Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common OR, 0.75; 95% CI, 0.60-0.92) but an increase in poor outcomes among patients with cerebral ischemia (common OR, 1.30; 95% CI, 1.06-1.60)
‘Slam-Dunk’ Effect
Anderson has led several previous trials of blood pressure control in stroke patients, some of which have suggested benefit of lowering blood pressure in those with hemorrhagic stroke, but he says the results of the current trial are more clear-cut.
“We have never seen such a slam-dunk effect as there was in INTERACT4,” Anderson said. “Not only did we show that early reduction of blood pressure in hemorrhagic stroke patients improved functional outcome, it also reduced bleeding in the brain, improved survival and quality of life, and reduced surgery and infection complications. That’s quite remarkable.”
The findings offer “clear evidence that for patients with hemorrhagic stroke, we must get the blood pressure under control as soon as possible and introduce systems of care to ensure this happens,” he added.
The reason for the clear findings in the current trial is probably the treatment time, Anderson said.
“This is the first trial in which blood pressure has been controlled in the ambulance and occurred much earlier than in the previous trials.”
Challenging Ischemic Stroke Guidelines
The INTERACT4 results in ischemic stroke patients are likely to be more controversial.
“Our results are clearly challenging longstanding beliefs around blood pressure control in ischemic stroke prior to thrombolysis,” Anderson says.
Current guidelines recommend a blood pressure
“Our results suggest this may not be a good idea,” Anderson said. “I think these data will shake us up a bit and make us more cautious about reducing blood pressure in these patients. Personally, I wouldn’t touch the blood pressure at all in ischemic stroke patients after these results.”
He says the mechanisms behind the different stroke types would explain the results.
“If a patient is bleeding, it makes sense that higher blood pressure would make that worse,” Anderson said. “But when a patient has a blocked artery and ischemia in the brain, it seems likely that the extra pressure is needed to keep oxygen delivery to the ischemic tissue.”
Accurate Diagnosis Necessary
Because it is not possible to make an accurate diagnosis between ischemic and hemorrhagic stroke without a CT scan, Anderson stresses that at the present time, no action on blood pressure can be taken in the ambulance.
“There is a lot of interest in developing a lightweight brain scanner to be used in ambulances, but this won’t be routinely available for several years,” he said. “So for now, quick diagnosis of the type of stroke that is occurring on the patient’s arrival at the emergency department and, for hemorrhagic stroke patients, swift action to control blood pressure at this point is critical to preserving brain function.”
Commenting on the INTERACT4 results at the ESOC meeting, Simona Sacco, MD, professor of neurology at the University of L’Aquila, Italy, said this was a very important trial that would impact clinical practice.
“The data really reinforce that hemorrhagic stroke patients must have their blood pressure reduced as soon as possible,” she stated.
Sacco said the trial emphasizes the need to be able to distinguish between a hemorrhagic and ischemic stroke in a prehospital setting and supports the introduction of more mobile stroke units carrying CT scanners and calls for the development of biomarkers that can allow rapid differentiation between the two conditions.
In an accompanying editorial, Jonathan Edlow, MD, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, points out several aspects of the trial that may potentially limit the generalizability of the findings. These include use of urapidil as the antihypertensive agent, which is unavailable in the United States; all patients being of Han Chinese ethnicity; and an unusually high sensitivity of initial CT scans in detecting visible signs of ischemia or infarction in patients in acute ischemic stroke.
“These findings should be considered hypothesis-generating, and they make the case for validation of the trial results in other settings,” Edlow wrote.
The INTERACT4 trial was funded by the National Health and Medical Research Council of Australia, the George Institute for Global Health, several Chinese healthcare institutions, and Takeda Pharmaceuticals China. Disclosures for study and editorial authors are provided in the original articles.
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