World Stroke Organization The Paper of The Month – June
26 Jun 2025Time Matters in ICH: New Pooled-Analysis Backs Early Intensive BP Lowering
Time Matters in ICH: New Pooled-Analysis Backs Early Intensive BP Lowering
Prof. Octavio Marques Pontes-Neto, MD, PhD – Editor-in-Chief, World Stroke Academy
This article is a commentary on the following: Effects of blood pressure lowering in relation to time in acute intracerebral haemorrhage: a pooled analysis of the four INTERACT trials, The Lancet Neurology, Volume 24, Issue 7, 571 – 579, https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(25)00160-7/abstract
Commentary:
The WSA highlighted paper of this month is a patient-level pooled analysis combining the four major randomized controlled trials of early blood pressure (BP) lowering in acute intracerebral hemorrhage (ICH): INTERACT1, INTERACT2, INTERACT3, and INTERACT4. Including over 11,000 patients, this individual patient-data (IPD) analysis delivers the most robust evidence to date on the safety and effectiveness of intensive BP-lowering therapy in ICH, with clear confirmation that time to treatment is critical.
The pooled analysis demonstrated that intensive BP lowering (target SBP <140 mmHg within 1 hour of randomization) significantly improved functional recovery and decreased the chances of poor physical function (mRS scores of 3–6; OR: 0·85, 95% CI 0·78–0·91). Notably, neurological deterioration within 7 days, death, and serious adverse events were all significantly reduced in the intensive treatment group. These benefits were not associated with increased risk of hypotension, renal impairment, or other safety concerns.
Previous trials had shown mixed results—with INTERACT2 suggesting benefit, ATACH-2 reporting neutral results, and INTERACT3 and INTERACT4 introducing pragmatic and prehospital strategies. This comprehensive analysis reconciles these discrepancies by revealing treatment timing as a key modifier of effect. It also confirms the safety of intensive BP lowering, even when initiated very early.
Importantly, subgroup analyses showed that the benefit of treatment decreased with increasing time from symptom onset, with a threshold effect around 3 hours. The functional benefit and reduction in hematoma growth (in a CT substudy) were only apparent when BP lowering was initiated within 3 hours, confirming the value of ultra-early intervention.
Despite these promising results, the analysis did not show a significant reduction in hematoma growth at 24 hours overall. The benefit may be mediated through mechanisms beyond hematoma expansion, such as reducing edema or secondary injury. Further studies are needed to optimize BP targets and evaluate patient-specific responses, including by hemorrhage location and severity.
In conclusion, the pooled results from INTERACT1–4 confirm that early, intensive BP lowering is safe and effective in acute ICH, with the greatest functional benefits observed when treatment is initiated within 3 hours. These findings should influence guideline updates and help shape future trials targeting patients at highest risk. Once again, stroke care delivers a clear message: time matters, in ICH too.
References:
Wang X, Ren X, Li Q, Ouyang M, Chen C, Delcourt C, Chen X, Wang J, Robinson T, Arima H, Ma L, Hu X, You C, Li G, Jie Y, Lin Y, Billot L, Muñoz-Venturelli P, Martins S, Pontes-Neto OM, Liu L, Chalmers J, Carcel C, Song L, Anderson CS; INTERACT Investigators. Effects of blood pressure lowering in relation to time in acute intracerebral haemorrhage: a pooled analysis of the four INTERACT trials. Lancet Neurol. 2025 Jul;24(7):571-579. doi: 10.1016/S1474-4422(25)00160-7. PMID: 40541207.
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