Systolic Blood Pressure Trajectory and Outcomes in Acute Intracerebral Hemorrhage: Pooled Analysis of the 4 INTERACT and ATACH-II Clinical Trials.

Six distinct systolic blood pressure trajectories were identified over the first 24 hours after acute intracerebral hemorrhage using latent class analysis.

• The six clusters were labeled: low, moderate-to-low, moderate, high, high-to-moderate, and high-to-low.
• Trajectories were derived from 9 SBP measurements over the first 24 hours post-randomization.
• The analysis was conducted on pooled individual patient-level data from 4 INTERACT trials and ATACH-II.
• A total of 11,269 patients were included (INTERACT n=10,269; ATACH-II n=1,000; mean age 62.4 years; 36.4% female).

Higher and more sustained SBP trajectories were progressively associated with worse functional outcomes at 90 days in the INTERACT cohort.

• Compared with the low SBP group, associations with poor functional outcome (mRS scores 3-6) increased progressively across other groups (p=0.04 for trend).
• Adjusted odds ratios (95% CI) for groups 2 to 6 were: moderate-to-low 1.16 (0.98-1.37), moderate 1.44 (1.18-1.75), high 1.46 (1.15-1.87), high-to-moderate 1.90 (1.32-2.73), and high-to-low 1.28 (1.02-1.60).
• The high-to-moderate group had the highest odds of poor functional outcome with an adjusted OR of 1.90 (95% CI 1.32-2.73).
• Logistic regression models were adjusted for baseline covariates and trial.

The severe hypertensive (high-to-moderate) SBP trajectory group had the highest odds of poor functional outcome regardless of blood pressure-lowering strategy used.

• The high-to-moderate group had an adjusted OR of 1.90 (95% CI 1.32-2.73) for mRS scores 3-6 compared to the low SBP group.
• This finding held regardless of the BP-lowering strategy employed.
• The paper provides Class III evidence for this association.
• Poor functional outcome was defined as modified Rankin Scale scores of 3-6 at 90 days after randomization.

A similar trend of worse outcomes with higher SBP trajectories was observed in ATACH-II but did not reach statistical significance.

• The trend in ATACH-II was described as 'similar albeit nonsignificant' compared to INTERACT.
• The lack of significance in ATACH-II was attributed to limited statistical power.
• The ATACH-II validation cohort comprised 1,000 patients.
• ATACH-II served as the validation dataset for associations found in the primary INTERACT analysis.

Large rapid reductions in SBP within 1 hour, such as reductions from >200 to <140 mmHg, were noted to diminish or reverse the beneficial effects of blood pressure lowering after ICH.

• Moderate and rapid SBP lowering was associated with better functional outcomes after ICH.
• Reductions from >200 to <140 mmHg within 1 hour specifically diminished or reversed these beneficial effects.
• This observation motivated the study's aim to define the optimal trajectory of SBP control.
• The high-to-low SBP trajectory group had an adjusted OR of 1.28 (95% CI 1.02-1.60) for poor functional outcome, suggesting that rapid large reductions were not as beneficial as sustained low SBP.

The study pooled individual patient-level data from five international randomized controlled trials examining early intensive SBP control in acute ICH.

• Trials included were INTERACT1 (NCT00226096), INTERACT2 (NCT00716079), INTERACT3 (NCT03209258), INTERACT4 (NCT03790800), and ATACH-2 (NCT01176565).
• All trials were described as 'international, randomized, open-label, blinded, end point-assessed, controlled trials.'
• Only patients with at least 1 post-randomization SBP reading were included, yielding a total of 11,269 patients.
• INTERACT trials contributed 10,269 patients and ATACH-II contributed 1,000 patients.