Lower Post-Stroke Blood Pressure Variability Is Associated With Better Functional Outcomes

Daniel M. Keller, PhD

November 10, 2016

HYDERABAD, India — Greater variability in systolic blood pressure (SBP) during the first 24 hours after an acute ischemic stroke not treated by thrombolysis is associated with worse functional outcomes at 3 months, a controlled clinical trial shows.

In this trial, high variability in blood pressure resulted in lower functional independence at 3 months, Sheila Martins, MD, PhD, from the Hospital de Clínicas de Porto Alegre, Brazil, told Medscape Medical News during a poster session here at the World Stroke Congress (WSC) 2016.

Patients maintained at lower blood pressures had lower systolic variability, "so I think if we decrease the blood pressure it's better," she said. "So we think, really, the best is lower blood pressure with low variability, too."

Her study was a subanalysis of the Manipulation of Systolic Blood Pressure in Acute Ischemic Stroke (MAPAS) trial, which investigated the association between the variability in SBP and functional outcomes at 3 months, defining a good outcome as a modified Rankin Scale (mRS) score of 0 to 2 among nonthrombolyzed patients with acute ischemic stroke.

The trial included patients older than age 18 years (n = 218; mean age, 69 years; 51% men) who presented to the emergency department less than 12 hours after symptom onset.

Patients were randomly assigned to three levels of SBP maintenance during the first 24 hours: 140 to 160 mmHg (n = 77), 161 to 180 mmHg (n = 75), or 181 to 200 mmHg (n = 66). Epinephrine, esmolol, nitroprusside, and fluids were used to achieve these levels.

There was no intervention if the presenting SBP was in the randomized range. Saline solution and norepinephrine were used to bring lower pressures up to this range, and esmolol and nitroprusside were used to bring higher pressures down to the randomized range.

The patient groups were similar in computed tomographic parameters at stroke onset and in stroke locations and subtype. After the first 24 hours, patients received antihypertensive therapy according to American Heart Association guidelines for acute stroke care.

The determination of SBP variability was estimated from 24 measurements in the first 24 hours, based on standard deviations, categorized into quintiles.

Lower Variability

About 50% of patients with SBP variability in the range of standard deviations of 6 to 14 mmHg in the first 24 hours showed good functional outcome at 3 months, with declines in the proportion of patients with good outcomes if they had greater SBP variability (P = .027, chi-square for trend).

Table. Good Outcome by SBP Variability in the First 24 Hours

SBP Variability (Standard Deviation, mmHg) Good Outcome (mRS Score, 0 to 2) (%)
6 - 12 (n = 43) 54
12 - 14 (n = 43) 56
14 - 16 (n = 44) 50
16 - 20 (n = 43) 44
20 - 40 (n = 43) 33

Patients with higher blood pressures had more intracranial bleeding and worse outcomes independent of the size of the infarction. "So increasing the blood pressure is a bad idea, and now we know this. A higher level of blood pressure may be a marker of worse strokes [for] patients arriving at the hospital," Dr Martins said.

She noted that in Brazil, physicians use esmolol and nitroprusside and that they do not have drugs to maintain good control of blood pressure, such as betalol and nicardipine.

Richard Lindley, MBBS, MD, professor of geriatric medicine at the University of Sydney, Australia, who is running the Enhanced Control of Hypertension and Thrombolysis Stroke Study (STAY ENCHANTED) looking at blood pressure lowering for thrombolyzed patients, commented on the study for Medscape Medical News.

"This study of nonthrombolyzed patients is very nice background data because it's telling us that the patients who got low blood pressure variability are doing better," Dr Lindley said. "We're hoping that controlling blood pressure in the acute phase of ischemic stroke could be a very good intervention because we know that if you treat blood pressure you are probably likely to reduce blood pressure variability."

He said Dr Martins' study strengthens the current work looking at blood pressure lowering in acute ischemic stroke. "It's a question we've been asking for decades: 'What's the blood pressure goal in ischemic stroke?'"

He noted that when he started in the field 30 years ago, clinicians were instructed "to leave the blood pressure alone." The Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT-2) has shown that blood pressure lowering in hemorrhagic stroke is very safe. "So the natural next question is, what's the blood pressure goal in ischemic stroke?" Professor Lindley asked.

He said Dr Martins' study adds to the accumulating data that blood pressure manipulation could be a very important, highly generalizable, cheap intervention for ischemic stroke.

Asked whether modifying blood pressure can modify its variability, Professor Lindley said, "I think if you are lowering blood pressure, you are likely to reduce variability. Therefore, this is some indirect evidence that blood pressure lowering is going to be useful."

There was no commercial funding of the study. Dr Martins and Professor Lindley have disclosed no relevant financial relationships. Professor Lindley was not involved in the present study, but Dr Martins is participating in his STAY ENCHANTED study.

World Stroke Congress (WSC) 2016. Abstract 083. Presented October 27, 2016.

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