Page 139 - Read Online

Page 12 of 20 Akinci et al. Vessel Plus 2021;5:56 https://dx.doi.org/10.20517/2574-1209.2021.20

standard treatment (target SBP 140-179 mmHg; n = 500) [48,68] . IV nicardipine (first line), labetalol, diltiazem
or uradipil were used. Time to start treatment in the intensive and standard treatment groups was 182.2 (±
57.2) min and 184.7 (± 56.7) min, respectively. 12.2% of patients in the intensive and 0.8% of patients in the
standard treatment group did not reach the target SBP within 2 h of randomization. The proportion of SAEs
within 72 h was low while the proportion of patients with any SAEs in the first 3 months and renal adverse
[48]
events within the first week was higher in the intensive treatment group .
Recently, post hoc analysis of the ATACH-2 trial results, which analyzed the effect of intensive (target SBP
110-139 mmHg) over standard (target SBP 140-179 mmHg) treatment in 682 moderate to severe grade
patients (Glaskow Coma Scale < 13 or baseline NIHSS ≥ 10 or presence of intraventricular hemorrhage) has
[69]
been published . According to study results, intensive treatment reduced the hematoma expansion
frequency (20.4% vs. 27.9%), but did not reduce the rate of death or disability.

[52]
Meta-analysis of Koch et al. , INTERACT, INTERACT-2, ADAPT, Gong et al. , ATACH-2, 2017
[66]
The meta-analysis reported similar incidence of 3-month SAEs between intensive (target SBP < 140 mmHg
or MAP < 110 mmHg) and conservative treatment groups . Despite including the ATACH-2 trial in which
[70]
higher renal adverse events were observed with intensive treatment in the first week, the incidence of 72 h
hypotension was similar in the two groups. Intensive BP reduction did not improve 24 h neurological
recovery or 3-month functional outcomes. Subgroup analysis showed that intensive BP lowering had
significant reducing effect on hematoma growth in age ≤ 62 years, treatment receiving time ≤ 6 h, initial
hematoma volume ≤ 15 mL, and combined intraventricular hemorrhage ≤ 25% subgroups.

[52]
Meta-analysis of Koch et al. , INTERACT, INTERACT-2, ICH-ADAPT, ATACH-2, 2017
This study included 2162 and 2188 participants in the intensive and conservative treatment groups,
respectively . The mean duration of treatment onset was greater than 3 h in all trials included in the meta-
[71]
analysis and target BP could not be achieved within 1 h in two-thirds of the patients in the intensive
treatment group. Early intensive BP reduction was safe and attenuated hematoma expansion, but did not
cause differences in 3-month mortality or major disability. Rates of early neurological deterioration,
hypotension, severe hypotension within 72 h, recurrent stroke, acute coronary events, or treatment-
emergent adverse events within 3 months were similar between two groups, but renal failure proportion was
higher in the intensive treatment group (weight: 81.74% ATACH-2, 18.26% INTERACT).

RIGHT-2, 2019
The Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke Trial (RIGHT) was an ambulance-
based pilot study . Transdermal GTN (5 mg/24 h) started by paramedics in probable ultra-acute (< 4 h)
[72]
stroke patients with SBP > 140 mmHg and continued for 7 days. Only 6 ICH patients enrolled. Results
showed that paramedics were able to successfully enroll patients, and GTN was safe and reduced SBP at 2 h
(153 ± 31 mmHg vs. 174 ± 27 mmHg).

The subsequent RIGHT-2 trial included 1149 patients with SBP ≥ 120 mmHg, within 4 h of symptom
onset . One hundred and forty-five patients were diagnosed with ICH, of whom 51.03% received GTN,
[73]
and 48.97% received sham. First treatment was administered by the paramedics, and further treatments
were given in the hospital for 3 days. Median randomization time was 74 min (interquartile range, 45-110)
and mean initial SBP was 176 ± 27 mmHg. BP at admission was lower in the GTN group (mean,
4.4/3.5 mmHg). SAE rate was similar, and the mRS score at day 90 was nonsignificantly higher in the GTN
group. Clinical outcomes including disability, cognition, dependency, life quality, and mood were worse
with GTN and death in hospital was increased with GTN. Hematoma size and growth, and midline shift
and mass effect on brain imaging were greater in the GTN group. Additionally, GTN was associated with