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Page 10 of 20 Akinci et al. Vessel Plus 2021;5:56 https://dx.doi.org/10.20517/2574-1209.2021.20

INTERACT, 2008
This pilot trial compared the effect of BP lowering on haematoma expansion . Four hundred and four ICH
[38]
patients with high SBP (150-220 mmHg) were randomized to an intensive treatment group (target SBP <
140 mmHg; n = 203) and a guideline-based BP treatment group (target SBP < 180 mmHg; n = 201) within
6 h of symptom onset. The lower limit of SBP required for discontinuation of antihypertensive treatment
was 130 mmHg. Variable antihypertensive agents were used in the study. In the intensive treatment group,
target SBP of 140 mmHg was achieved in 42% of patients within 1 h and 66% of patients within 6 h.
Intensive BP reduction resulted in less increase in hematoma volume (absolute risk reduction: 8%) and was
found clinically feasible and well tolerated.

ATACH, 2010
In the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) trial treatment failure, early
neurologic deterioration, and serious adverse event (SAE) within 72 h of the groups with target SBP of 170-
200 mmHg, 140-170 mmHg and 110-140 mmHg were investigated . Sixty ICH patients, within first 6 h
[58]
after symptom onset, with SBP ≥ 170 mmHg were included and IV nicardipine was used. The average
duration from symptom onset to start of treatment was 3.94 h, 4.13 h and 4.44 h, respectively. In 90% of
patients, SBP targets were achieved within 2 h. Neurological deterioration and SAE rates were lower than
expected in each group according to pre-determined thresholds. The magnitude of SBP reduction was
associated with attenuation of hematoma enlargement and poor three-month outcomes (the rates were 21%
vs. 31% for hematoma enlargement, and 35% vs. 48% for poor three-month outcomes with SBP reduction of
> 54 mmHg compared with ≤ 54 mmHg at 2 h) .
[54]

ICH ADAPT, 2013
The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT) tested whether BP
reduction in acute ICH patients affected CBF. ICH patients within 24 h of symptom onset, with SBP >
150 mmHg were randomized to a treatment group targeting a SBP of < 150 mmHg (n = 39) or < 180 mmHg
(n = 36). Labetalol, hydralazine and enalapril were used. Despite similar initial SBP, mean SBP after 2 h was
significantly lower in the intensive treatment group (140 ± 19 mmHg vs. 162 ± 12 mmHg). Perihematomal
relative CBF was similar in both groups. Although the study was underpowered to compare these events,
[59]
ICH volume growth, mortality, and disability scores were all similar between two groups .

INTERACT-2, 2013
In the INTERACT-2 trial, ICH patients with SBP 150-220 mmHg were randomized to intensive BP
treatment (target SBP < 140 mmHg; n = 1399) or conservative BP treatment group (target SBP < 180 mmHg;
n = 1430). Patients were within 6 h of onset and average time between symptom onset and treatment
initiation was 4 (2.9-5.1) h and 4.5 (3-7) h, in the intensive and conservative treatment groups,
respectively . In the intensive treatment group, target SBP was not achieved in the 66.6% of patients within
[49]
1 h. Intensive BP reduction was safe but did not cause a statistical significance in the major disability or
death rate, but a secondary analysis of ordinal modified Rankin Scale (mRS) showed that intensive BP
reduction led to better physical functional outcomes compared with conservative treatment.

In the CT substudy, which included 964 (40%) patients of INTERACT-2, baseline and 24 ± 3-h CT images
[60]
of the brain were analyzed . Results showed that intensive SBP reduction (target SBP < 140 mmHg) was
achieved within 1 h and consistently maintained, and protected against hematoma enlargement for 24 h. Of
491 patients randomized to intensive BP reduction, the least hematoma expansion occurring in patients
reached target SBP early (≤ 1 h, 2.6 mL; 1 to 6 h, 4.7 mL and > 6 h, 5.4 mL). Greater reduction in SBP
resulted in less hematoma expansion (for < 10 mmHg, 13.3 mL; 10-20 mmHg, 5.0 mL and ≥ 20 mmHg,
3.0 mL).