Blood Pressure Treatment Reduces Bleeding in ICH

Erik Greb

November 19, 2020

Lowering blood pressure for patients with intracerebral hemorrhage (ICH) does not improve functional recovery, a systematic review and meta-analysis shows, although it does reduce hematoma growth in these patients.

Despite the negative finding, the investigators observed broad variation in treatment effect among the studies they reviewed. They also found that target-based blood pressure treatment tended to improve function more than fixed-dose treatment.

"These data provide a strong message that early blood pressure lowering treatment can control bleeding. This was not clear beforehand," Craig Anderson, PhD, professor of neurology and epidemiology at the University of New South Wales, Sydney, Australia, told Medscape Medical News.

"But these data also indicate that the management of blood pressure in ICH is complex," he added. Timing, type of drug, and type of patient must be considered, he said. "We need more data to allow better individualizing of such therapy."

The results were presented at the European Stroke Organisation–World Stroke Organisation (ESO-WSO) Conference 2020.

Controversy about the efficacy of blood pressure reduction for patients with ICH continues, despite studies that have examined this question. In this analysis, Anderson and colleagues sought to examine the evidence from randomized controlled trials in this area and identify potentially overlooked heterogeneity among trials.

The investigators conducted a systematic review and meta-analysis of studies in the Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE databases. They searched for randomized controlled trials of blood pressure management for adults with acute ICH, focusing on studies in which patients were enrolled within 7 days of ICH onset. These studies compared intensive blood pressure management with guideline-based management.

Investigators chose function, defined as Modified Rankin Scale (mRS) score at 90 days, as their primary outcome. Radiologic outcomes included absolute (>6 mL) and proportional (>33%) hematoma growth at 24 hours. They used the intention-to-treat dataset from each trial in their statistical analyses and created generalized linear mixed models with prespecified covariables using a one-stage approach.

Variation by Drug

A total of 7094 studies were identified, of which 50 were eligible for inclusion. Their analysis encompassed 16 studies for which the respective investigators were willing to share patient-level data. The analysis included data on 6221 patients. The mean age of the patients was 64.2 years, 36.4% were women, and the median time from symptom onset to randomization was 3.8 hours.

Mean NIH Stroke Scale score was approximately 11. Mean systolic blood pressure at baseline was 177 mmHg, and mean hematoma volume was approximately 10.6 mL.

The difference in blood pressure between the intensive and guideline groups was approximately 8 mmHg at 1 hour and 12 mmHg at 24 hours.

Intensive blood pressure management did not affect function at 90 days. The adjusted odds ratio (aOR) for unfavorable shift in mRS scores was 0.97 (95% CI, 0.88 – 1.06; P = .503).

Intensive blood pressure management did, however, reduce hematoma growth (absolute aOR, 0.75; 95% CI, 0.60 – 0.92; P = .007; relative aOR, 0.82; 95% CI, 0.68 – 0.99;, P = .034).

In prespecified subgroup analyses, they found a trend toward adverse outcomes among patients who received renin-angiotensin blockers and a trend toward benefit for patients who received alpha- or beta-receptor antagonists or calcium channel blockers. They did not observe a clear association between time of treatment and outcome.

In addition to hematoma growth, other factors influence prognosis after ICH, such as the patient's status before ICH (for example, cardiovascular risk factors; age; and hypertensive effects on the brain, kidneys, and heart), the location of ICH and its effects on surrounding structures, and complications of care in hospitals, such as infection and bleeding, said Anderson.

They are conducting two ongoing clinical trials in patients with ICH. One, INTERACT3, is evaluating a "care bundle" quality control package that includes early intensive blood pressure lowering for patients with large ICH who undergo surgery.

The other, INTERACT4, is evaluating early blood pressure control in the ambulance for patients with suspected acute stroke. At least one fifth of those patients will have ICH, said Anderson.

Prevention Is Essential

Among patients with ICH, much of the bleeding occurs before presentation at the hospital, Louis R. Caplan, MD, a neurologist at Beth Israel Deaconess Medical Center, Boston, Massachusetts, told Medscape Medical News. Furthermore, the bleeding mainly occurs in the deep part of the brain where most of the important motor tracts are. "If those tracts are already hit, a little extra blood isn't going to change things," said Caplan.

In addition, blood is pushed from inside the brain to the periphery until the pressure outside the brain is equal to the pressure inside it. "You can decrease the amount of bleeding significantly, but it probably doesn't affect the outcome," said Caplan.

One factor in patients' apparent lack of functional improvement is that the mRS is not sensitive to minor changes in disability, he said. "You have to show a pretty important change for it to make a difference," said Caplan.

In addition, recovery from a hemorrhage takes much longer than recovery from an infarct. Examining the population at 6 months would have been preferable to examining them at 90 days, but the investigators might not have 6-month data, said Caplan.

"The main thing is really prevention," he concluded.

The study was conducted with funding from Takeda. Anderson reported receiving funding from the National Health and Medical Research Council of Australia and speaker fees from Takeda. Caplan has disclosed no relevant financial relationships.

European Stroke Organisation–World Stroke Organisation (ESO-WSO) Conference 2020. Presented November 8, 2020.

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