J-shape relation of blood pressure reduction and outcome in acute intracerebral hemorrhage: A pooled analysis of INTERACT2 and ATACH-II individual participant data

Abstract

Objective: The aim of this study was to better define the shape of association between the degree (“magnitude”) of early (< 1 h) reduction in systolic blood pressure (SBP) and outcomes in patients with acute intracerebral hemorrhage (ICH) through pooled analysis of the second Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) and second Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II) datasets. Methods: Association of the continuous magnitude of SBP reduction described using cubic splines and an ordinal measure of the functional outcome on the modified Rankin scale (mRS) scores at 90 days were analyzed in generalized linear mixed models. Models were adjusted for achieved (mean) and variability (standard deviation, SD) of SBP between 1 and 24 h, various baseline covariates, and trial as a random effect. Results: Among 3796 patients (mean age 63.1 (SD = 13.0) years; female 37.4%), with a mean magnitude (< 1 h) of SBP reduction of 28.5 (22.8) mmHg, those with larger magnitude were more often non-Asian and female, had higher baseline SBP, received multiple blood pressure (BP) lowering agents, and achieved lower SBP levels in 1–24 h. Compared to those patients with no SBP reduction within 1 h (reference), the adjusted odds of unfavorable functional outcome, according to a shift in mRS scores, were lower for SBP reductions up to 60 mmHg with an inflection point between 32 and 46 mmHg, but significantly higher for SBP reductions > 70 mmHg. Similar J-shape associations were evident across various time epochs across 24 h and consistent according to baseline hematoma volume and SBP and history of hypertension. Interpretation: A moderate degree of rapid SBP lowering is associated with improved functional outcome after ICH, but large SBP reductions over 1 h (e.g. from > 200 to target < 140 mmHg) were associated with reduction, or reversal, of any such benefit.

Hypertensive crisis: diagnosis, presentation, and treatment

“…Despite this, two large randomized trials, INTERACT2 and ATACH-II, comparing BP goals of less than 140 mmHg to less than 180 mmHg, have failed to show mortality or functional benefit [41,42]. A recent meta-analysis of both of these trials, however, found a J-shaped curve, with an inflexion point and improved functional outcomes when SBP was reduced between 32 and 46 mmHg within the first hour and worse functional outcomes when SBP was reduced over 60 mmHg [43 ▪▪ ]. Thus similar to findings of BP reduction post mechanical thrombectomy, there appears to be a benefit with modest lowering and harm at greater amounts.…”

Bringing High-Dose Neurorestorative Behavioral Training Into the Acute Stroke Unit

“…This led to the development of a progressive activity algorithm used in the neurocritically ill population and providing safety boundaries for this progression 31 . Using this approach, we have successfully implemented progressive verticalization to safely introduce high-intensity recovery activities in a population of patients prone to autonomic dysfunction 32–34 …”

“…31 Using this approach, we have successfully implemented progressive verticalization to safely introduce high-intensity recovery activities in a population of patients prone to autonomic dysfunction. [32][33][34] Intracranial hypertension is another safety issue for consideration in increasing early activity protocols for hospitalized patients with both ischemic and hemorrhagic stroke. Therefore, attention to this physiological variable when considering the addition of high-intensity activity is essential.…”

Review of Long-Term Blood Pressure Control After Intracerebral Hemorrhage: Challenges and Opportunities

“…44 Secondary analysis of ATACH-II indicates adverse events were more frequent in patients in the intensive arm who had their SBP reduced from ≥220 mm Hg to <140 mm Hg, 45 which has been supported by further analysis of the pooled dataset showing an increase in adverse outcomes with a large magnitude of SBP lowering (>60 mm Hg within 1 hour). 46 Most patients who were included in both these RCTs had deep ICH, but the response to BP lowering may differ by location of the hematoma. 47…”