Early BP Variability After ICH Predicts Disability

Erik Greb

September 03, 2021

Greater short-term variability in systolic blood pressure after intracerebral hemorrhage (ICH) is associated with an increased risk for long-term disability, new research suggests.

A pooled analysis of randomized controlled trials indicated that each 10 mmHg increase in standard deviation of systolic blood pressure variability was associated with an 18% increase in the likelihood of functional impairment at 90 days. The association was stronger among patients undergoing intensive blood pressure-lowering treatments.

"Our findings provide support for careful, sustained blood pressure lowering early after acute ICH, especially in patients who receive early intensive blood pressure lowering according to the new European Stroke Organisation guidelines and several other international guidelines," study author Tom Moullaali, PhD, honorary clinical senior lecturer at the University of Edinburgh in the United Kingdom, told Medscape Medical News.

The findings were presented at the European Stroke Organization Conference (ESOC) 2021, which was held online.

Meta-analysis of BASC Trials

ICH carries a high risk for mortality, and most patients who survive develop lasting disability, the investigators note.

In a previous systematic review and meta-analysis, the researchers found an association between higher systolic blood pressure variability and poor functional outcome after acute ICH. Every 10mmHg increase in the standard deviation (SD) of systolic blood pressure was associated with an approximately 40% increase in the odds of poor function at 90 days.

This analysis had limitations, however. "Several included studies did not adjust for confounding from mean blood pressure during treatment," Moullaali said. "None explored heterogeneity in the association according to characteristics of the blood pressure lowering interventions that patients received."

To reexamine this question, the investigators pooled data for participants in randomized controlled trials that were included in the Blood Pressure in Acute Stroke Collaboration (BASC). The latter initiative seeks to identify the best method of managing blood pressure after acute stroke.

For this analysis, the researchers defined short-term systolic blood pressure variability as the SD of systolic blood pressure measures from hours 1 through 24 after randomization. The primary outcome of the analysis was function, defined as the distribution of scores on the modified Rankin Scale (mRS), at 90 to 180 days after randomization.

The investigators used a one-stage approach for their meta-analysis and adjusted the data for prespecified covariables, other summary measures of systolic blood pressure control, and trial. They also examined the interaction effect of blood pressure-lowering agent and blood pressure-lowering strategy.

"New Information"

The researchers identified 6221 patients, and the minimum data needed for adjusted analyses were available for 5463 (88%) of this group. Median time to randomization was 4 hours after the stroke.

They observed a linear association between short-term systolic blood pressure variability during 24 hours after randomization and functional outcome. For each 10mmHg increase in SD of systolic blood pressure, the adjusted odds ratio (OR) of an unfavorable shift in ordinal mRS scores was 1.18 (P < .001).

In addition, the investigators found significant interactions (P < .001) for commonly used blood pressure-lowering agents, including alpha- and beta-adrenoreceptor blockers (OR, 1.30), calcium channel blockers (OR, 1.51), magnesium sulfate (OR, 1.05), and nitrate (OR, 1.05).

They also observed significant interactions (P < .001) for the titrated target-based blood pressure-lowering strategy (OR, 1.32) and for the fixed class-based blood pressure-lowering strategy (OR, 1.04).

The researchers' dataset included patients from 16 high-quality randomized controlled trials in the BASC. "This allowed extensive adjustment for relevant confounding factors," Moullaali said. "We were also able to explore heterogeneity in the association according to time to treatment, agent, strategy, and degree of blood pressure lowering. Therefore, our findings provide new information to clinicians."

"Time for New Strategies"  

"Patterns of blood pressure in the first 24 hours after ICH may prove to be important in our quest to stunt acute ICH size and improve functional and other outcomes associated with ICH," said Philip B. Gorelick, MD, MPH, adjunct professor of vascular neurology and neurocritical care at Northwestern University Feinberg School of Medicine in Chicago, who commented on the findings for Medscape Medical News.

The current findings show that drug classes such as alpha and beta adrenoreceptor blockers and calcium channel blockers may adversely influence long-term functional outcomes, Gorelick said.

"Interestingly, it has been proposed that increased sympathetic tone may be present in a number of important systemic vascular beds when there is acute ICH, and therefore, alpha and beta blockers could be beneficial," he added. "Thus, it may be important to understand the status of key vascular beds in relation to sympathetic tone."

Although data from clinical trials show that lowering systolic blood pressure is generally safe in patients with acute ICH, major trials have not found a benefit of this treatment on their primary outcomes. "Thus, it is time for new strategies, and these data provide guidance for a new direction in relation to the blood pressure pattern, systolic blood pressure variability," Gorelick said.

Until new data become available, it is advisable for clinicians to follow the available standard expert guidance on blood pressure-lowering in acute ICH, he added. "However, it may be reasonable to consider practice strategies to reduce systolic blood pressure variability, which may be attempted by use of certain continuous infusion blood pressure lowering agents rather than by use of intermittent bolus dosing agents in the early phase of acute ICH."

The study was supported by a British Heart Foundation clinical research training fellowship. Moullaali disclosed no relevant financial relationships. Gorelick serves on a data-monitoring committee for a clinical trial of LCZ 696, a blood pressure lowering agent, in heart failure.

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