A trial called ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage II), recently published in NEJM, is likely to temper the enthusiasm for aggressively lowering blood pressure in patients with intracranial bleeds.
An immediate hypertensive response is common in patients with intracerebral haemorrhage. Many physiscians insist on aggressively lowering BP in these patients, reasoning that hypertension may cause haematoma expansion and increased mortality.
That never really made sense to me. Possibly because I never really understood brain perfusion physiology. Possibly because it doesn’t make sense. In any case, my brain hurts from even thinking about it.
ATACH-2 was a randomised, multicenter (110 sites) study comparing intensive vs. standard intravenous hypertensive treatment in patients with non-traumatic intracerebral bleeds. Randomisation and treatment was initiated within 4,5h of presentation. Eligible patients were adult patients with a GCS >5, with an intraparenchymal haematoma of <60 cm3 who had at least one reading of systolic blood pressure of >180 mmHg after symptom onset.
Patients were randomised to either standard or intensive treatment for 24 hours. Standard treatment meant lowering systolic BP to 140-179 mmHg while intensive treatment meant 110-139 mmHg. The mean interval between onset and treatment was ≈180 minutes for both groups. BP was lowered using primarily nicardipine or labetalol.
The primary outcome was the proportion of patients who had death or severe disability at three months. Secondary outcomes were, amongst others, expansion of the haematoma of 33% or more and functionality scoring at three months.
The trial was discontinued for futility after enrolling n=500 in each arm at a stage where the absolute difference in primary outcomes was less than 1%. There was no significant difference. Death and severe disability was 38.7% in the intensive-treatment group and in 37.7% in the standard-treatment group. Nor was there any difference in haematoma expansion or quality of life as measured by an EQ-5D self-assessment tool.
The ICH ADAPT, INTERACT 1 and INTERACT 2 trials demonstrated how lowering SBP to < 140-150 mmHg was safe, perihematomal blood flow was preserved and did not increase mortality or rates of dependency or neurological deterioration when compared to standard treatment control groups ~ SBP <180).
However, only INTERACT2 could demonstrate a tendency (non-significant) towards improved functional recovery with intensive BP lowering (NNT=28 to avoid major disability or death).
Sakamoto et al. in the in the SAMURAI study, reviewed 211 patients with ICH and hypertension with SBP > 180 mmHg who had nicardipine to achieve SBP < 160 mm Hg. The authors noted how functional 3 month outcomes were best in patients where SBP < 130 was achieved.
ATACH-2 is similar to the previous INTERACT2 trial. INTERACT 2 could display a marginal tendency towards benefit with aggressive treatment. ATACH-2 builds on that as the researchers recruited patients with higher BPs and started treating earlier (4,5 vs 6h), hoping to amplify the trend seen in INTERACT2. Unfortunately, ATACH-2 could demonstrate no incremental benefit.
For me this means I will keep treating high blood pressures in patients with intracranial bleeds, perhaps aiming for the upper normal range. Not because I think it will improve neurological outcome but out of concern for other organ systems. These patients are often old and have comorbidities and might not tolerate high BPs for long.
Study lives here:
N Engl J Med. 2016 Jun 8. [Epub ahead of print] Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. Qureshi AI1, Palesch YY1, Barsan WG1, Hanley DF1, Hsu CY1, Martin RL1, Moy CS1, Silbergleit R1, Steiner T1, Suarez JI1, Toyoda K1, Wang Y1, Yamamoto H1, Yoon BW1; ATACH-2 Trial Investigators and the Neurological Emergency Treatment Trials Network.
And you need to read:
JE on PulmCCM wrote an elegant, frustrated and critical post on ATACH-2. Read it here. He even channels Shakespeare: