Systolic BP Trajectory and Outcomes in Intracerebral Hemorrhage
- Acute blood pressure (BP) lowering to reduce hematoma growth and improve outcomes in intracerebral hemorrhage (ICH) seems to make instinctive sense, but the clinical trial evidence to support this approach is mixed.
- BP in ICH is notoriously difficult to study because of its minute-to-minute variability and the fact that high BP can be both a cause and an effect of ICH, leading to questions about causation versus correlation when clinical outcomes are considered.
- In this post hoc analysis of the ATACH-2 trial (2016), a systolic BP trajectory from high to low was associated with worse clinical outcomes in a cohort of patients presenting with ICH.
- Many providers outside of the stroke community are surprised to learn that acute BP goals for spontaneous ICH remain so unclear.
What is the association between early systolic blood pressure (SBP) change and clinical outcomes in patients presenting with intracerebral hemorrhage (ICH)?
This is a post hoc analysis of the ATACH-2 trial (2011-2015), which was an open-label randomized controlled trial of patients with acute spontaneous ICH with SBP ≥180 mm Hg on hospital arrival. Patients were randomized to either intensive SBP lowering to target 110-139 mm Hg or to standard SBP lowering to target 140-179 mm Hg. Nicardipine infusion was the first-line agent used. SBP was recorded every 15 minutes for the first 1 hour followed by every 1 hour for the next 23 hours. For this post hoc analysis, subjects were classified into one of four BP trajectory groups based on presenting BP and post-randomization BP:
- Reference: Moderate SBP (~190 mm Hg) → Low SBP (<140 mm Hg)
- Moderate SBP (~190 mm Hg) → Moderate SBP (150-160 mm Hg)
- High SBP (>210 mm Hg) → Low SBP (<140 mm Hg)
- High SBP (>210 mm Hg) → High SBP (160-170 mm Hg)
A measure of post-stroke disability (modified Rankin Scale score [mRS]) was collected for each patient at 3 months by blinded investigators. The primary outcome was poor mRS score or death at 3 months.
The study population consisted of 1,000 subjects. Patients in the high SBP → low SBP group (group 3 above) had an increased risk of death or disability at 3 months (adjusted odds ratio, 2.29; 95% confidence interval, 1.24-4.26) as well as acute kidney injury and cardiac adverse events within 7 days. The outcomes for the other groups (2 and 4 above) did not differ from the reference group.
In this post hoc analysis of the ATACH-2 trial, a SBP trajectory from high to low was not associated with positive clinical outcomes in a cohort of patients presenting with ICH. This finding runs counter to what many would expect.
Many providers outside of the stroke community are surprised to learn that acute BP goals for spontaneous ICH remain unclear in 2022. While the INTERACT2 trial (2013) suggested that acute lowering of SBP to <140 mm Hg is safe and possibly associated with improved functional outcomes, the ATACH-2 trial (2016) showed no difference in outcomes between the standard and intensive SBP lowering arms and found adverse renal outcomes in the intensive arm. The appropriate BP goal in acute ICH is likely to remain controversial in the stroke community for years to come.
Keywords: Acute Kidney Injury, Antihypertensive Agents, Blood Pressure, Cerebral Hemorrhage, Hematoma, Hypertension, Nicardipine, Outcome Assessment, Health Care, Primary Prevention, Stroke, Vascular Diseases
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