Abstract
Background and purpose: We aimed to highlight temporal trajectories of systolic blood pressure (SBP) in patients with acute intracerebral hemorrhage (ICH) to investigate the clinical relevance of heterogeneity in responses to blood pressure lowering therapy. Methods: A post-hoc analysis of ATACH-2 trial, in which ICH patients were randomly assigned to intensive or standard SBP lowering with intravenous administration of nicardipine. Using data for all 1000 patients enrolled from 110 clinical sites, temporal changes of hourly maximum SBP up to 24 hours after randomization were analyzed with the group-based trajectory modeling (GBTM). Model selection was mainly based on the Bayesian Information Criteria. The primary outcome was death or disability (modified Rankin Scale score 4-6) at 3 months. Secondary outcomes included hematoma expansion within 24 hours and acute kidney injury (AKI). AKI was defined as an increase in serum creatinine by ≥0.3 mg/dl or to ≥1.5 times baseline within 48 hours. The outcomes were compared between the trajectory groups using multivariable logistic models with random-effects by clinical sites. Results: Of the analyzed 1000 patients, death or disability, hematoma expansion, and AKI were encountered in 367, 161, and 101 patients, respectively. GBTM revealed 4 SBP trajectory groups: early response-low SBP (38.2%), moderate SBP (16.8%), delayed response-low SBP (14.2%), and high SBP (30.8%). Nicardipine dosage was highest in the delayed response-low SBP group, 81.7% of which were from the intensive SBP lowering group. The risk of death or disability was higher only in the delayed response-low SBP group (adjusted odds ratio [aOR] 2.86; 95% confidence interval [CI] 1.66-4.93) than in the early response-low SBP group. The risk of hematoma expansion was not significantly different among the groups. The delayed response-low SBP group had higher risk of AKI (aOR 2.78; 95% CI 1.46-5.31; reference, the early response-low SBP group). Conclusions: An SBP trajectory group with delayed SBP lowering despite intensive treatment was associated with increased risk of death or disability at 3 months. Resistance to intensive SBP lowering may predict poor clinical outcomes, and intensive SBP control in these cases will increase the risk of AKI.
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