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Akinci et al. Vessel Plus 2021;5:56 https://dx.doi.org/10.20517/2574-1209.2021.20 Page 13 of 20

altered use of hospital resources.

ICH ADAPT-2, Ongoing
This study, which is the phase II trial of ICH ADAPT, will assess ischemic lesion development in ICH
patients within 6 h of symptom onset, with a SBP target of < 140 mmHg and < 180 mmHg . Patients will
[74]
be treated with IV labetalol, hydralazine or enalapril and diffusion weighted imaging will be used. The study
is not yet complete.

Incorporation of results of randomized clinical trials and meta-analyses into clinical practice issues
Treatment threshold and target blood pressure
The INTERACT trial results indicated intensive BP lowering attenuated hematoma growth, and even target
SBP of < 140 mmHg was achieved only in the 42% and 66% of patients within 1 h and 6 h after
randomization, respectively . The INTERACT-2 trial included patients with SBP ≥ 150 mmHg and only
[38]
33.4% of patients in the intensive treatment group achieved the target SBP of < 140 mmHg at 1 h post-
randomization and the SBP profile reflected values close to 140 mmHg . According to post hoc analysis of
[49]
INTERACT-2 trial, having an average SBP of 130 mmHg at selected time points within 24 h after
randomization was associated with the lowest probability of death and disability at three months . On the
[49]
other hand, follow-up analysis of INTERACT-2 trial reported increase in the risk of death and major
disability with SBP of 120 mmHg compared to 130 mmHg . In the ATACH-2 trial, the mean minimum
[62]
SBP during the first 2 h was 141.1 ± 14.8 mmHg and 128.9 ± 16 mmHg in the standard treatment group and
intensive treatment group, respectively. Intensive treatment showed no clinical benefit and, moreover, it
was associated with a higher rate of renal adverse events and SAEs within the first 3 months .
[68]

In the meta-analysis of Koch et al. , INTERACT, ICH ADAPT, INTERACT-2 trials, intensive BP-lowering
[52]
treatment (target MAP < 110 mmHg, or SBP < 150 mmHg) reduced 3-month mortality and dependency
[63]
and provided a greater reduction in hematoma growth at 24 h compared with guideline treatment . In the
[52]
meta-analysis of Koch et al. , INTERACT, INTERACT-2, ADAPT, Gong et al. , ATACH-2 trials,
[66]
intensive BP lowering (target SBP < 140 mmHg or MAP < 110 mmHg) showed no effects on 24 h
neurologic improvement and 3-month functional outcome, and only attenuated hematoma growth in
patients age ≤ 62 years with hematoma volume ≤ 15 mL received treatment within 6 h after symptom
[70]
[55]
onset . In the meta-analysis including Koch et al. , INTERACT, INTERACT-2, ICH-ADAPT, ATACH-2
trials, no obvious benefit of intensive BP lowering was observed and the rate of renal failure was higher with
intensive treatment [driven predominantly by the trial with lowest SBP target (110-139 mmHg)] .
[71]
In summary, the results of two phase III trials (ATACH-2 and INTERACT-2) with larger sample sizes than
other studies, and a meta-analysis that included these two trials indicated that reaching a target below
130 mmHg may not be beneficial, but may be harmful. Therefore, available evidence supports the safety of a
treatment that aims to keep SBP between 130 and 150 mmHg. However, due to the risk of precipitating
cerebral hypoperfusion, studies are needed to investigate the safety of this target in patients with large
hematomas, ICP elevation, and impaired cerebral perfusion pressure.

Therapeutic window
Although ICH is likely to have a wider therapeutic window due to the absence of ischemic penumbra,
therapeutic window in ICH patients is still short, as the hematoma expansion mostly occurs within the first
few hours. Recombinant Factor VIIa in Acute Intracerebral Haemorrhage (FAST) trial showed that
treatment with rfVIIa reduced the rate of hematoma expansion when initiated within the first 4 h and
reduced even greater if this time was limited to 2.5 h . Data from the ATACH trial also showed that even
[20]
reduction of SBP within 4.5 h after symptom onset resulted in lower hematoma expansion and lower