Qureshi AI, Huang W, Lobanova I, et al. Outcomes of Intensive Systolic Blood Pressure Reduction in Patients With Intracerebral Hemorrhage and Excessively High Initial Systolic Blood Pressure: Post Hoc Analysis of a Randomized Clinical Trial [published online ahead of print, 2020 Sep 8]. JAMA Neurol. 2020;e203075. doi:10.1001/jamaneurol.2020.3075
Reviewed by Shannon Hextrum, MD
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The American Heart Association and American Stroke Association guidelines endorse the safety of lowering systolic blood pressure (SBP) to 140 mm Hg in patients with intracerebral hemorrhage (ICH) who present with SBP 150 and 220 mm Hg as a Class I recommendation, with Level of Evidence A, but evidence is less robust for ICH patients who present with excessively high SBP (SBP >220 mm Hg). To address this question, Qureshi, et al. conducted a post hoc analysis of ATACH-II (Antihypertensive Treatment of Acute Cerebral Hemorrhage- II) to explore outcomes of intensive SBP treatment in this population.
ATTACH-II was a multicenter, open-label randomized trial comparing intensive SBP reduction (110 to 139 mm Hg) vs. standard (140 to 179 mm Hg) in patients with spontaneous supratentorial ICH. The study required one SBP of ≥180 mm Hg between onset of symptoms and treatment, and there was no upper limit set on the initial SBP for inclusion in the trial. Antihypertensive treatment was permitted prior to randomization, and all patients required randomization and treatment within 4.5 hours of symptom onset. The primary outcome in ATACH-II was severe disability (modified Rankin scale score ≥4) or death at 90 days, and there was no significant difference between treatment groups. This subset analysis analyzed the patients from ATACH-II who presented with initial SBP ≥220 mm Hg, comparing clinical, demographic and outcome measures between intensive and standard SBP groups.
228 patients presented with initial SBP of ≥220 mm Hg, of which 110 received intensive BP reduction (110 – 139 mm Hg) vs. 118 who received standard BP reduction (140 – 179 mm Hg). These two groups had no statistically significant difference in the following: (1) percentage of severe disability or death at 90 days, (2) hematoma expansion in 24 hours and (3) rate of patients with serious adverse events. There was a higher percentage of patients with neurologic deterioration in the first 24 hours for the intensive lowering group (15.5%) vs. the standard reduction group (6.8%) (RR 2.28 [95% CI, 1.03-5.07] P = 0.04). Those patients in the intensive SBP reduction group also experienced significantly higher percentages of kidney adverse events (13.6%) vs. the standard treatment group (4.2%); RR 3.22 [95% CI, 1.21 – 8.56]; P = 0.01. The excessively high initial SBP group as a whole did not have a higher rate of death nor severe disability at 90 days when compared to the <220 mm Hg group. The entire group with SBP ≥ 220 mm Hg showed a lower percentage of hematoma expansion at 24 hours compared with those <220 mm Hg. Of the 771 patients with SBP <220 mmHg on presentation, 390 received intensive SBP reduction, while 381 received standard reduction. Hematoma expansion at 24 hours was lower in the intensive group compared to the standard care group (20.9% vs. 29.2 %, P = 0.009). The percentage of kidney adverse events was significantly greater in the intensive group vs. standard reduction group (7.7 % vs. 3.9%, P = 0.03).
Those patients with initial SBP of ≥220 mm Hg showed worse neurologic outcomes at 24 hours when randomized to intensive SBP reduction, despite similar rates of hematoma expansion between the intensive and standard SBP reduction groups. This finding suggests a separate mechanism of neurologic decline independent of hematoma expansion, and authors raise the possibility of cerebral ischemia as an underlying etiology for worse outcomes.
Despite these results at 24 hours, those patients with initial SBP ≥ 220 mm Hg who received intensive SBP lowering did not have higher death or severe disability at 90 days. This result at 90 days is consistent with the overall primary outcome in ATACH-II. In this current analysis, each of the initial SBP groups showed higher renal adverse events at 7 days when randomized to the intensive blood pressure reduction treatment.
While this study is limited by the post hoc nature of the analysis, the results are impactful for a number of reasons. Trial data in patients with ICH and excessively high initial SBP is limited, and it is worth noting that the INTERACT2 trial was designed to exclude patients with systolic BP >220 mm Hg. Thus, the subgroup of patients from ATACH-II with initial SBP ≥ 220 mm Hg should be considered carefully. This study suggests that aggressive SBP lowering provides no benefit in decreasing rates of hematoma expansion, and may actually cause harm, as reflected in neurologic deterioration at 24 hours. Although the 90-day outcome data did not show a difference between groups, the 24-hour neurologic decline and the adverse kidney events in the intensive group suggests harm in targeting early SBP <140 mm Hg in ICH patients with excessively high initial SBP.