ATACH-2 Trial

[https://www.ncbi.nlm.nih.gov/pubmed/27276234 Qureshi AI, Palesch YY, Barsan WG, et al. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. N Engl J Med 2016;375:1033–43.]

Clinical Question
In patients with spontaneous intraparenchymal hemorrhage (IPH), does intensive blood pressure (BP) lowering to systolic blood pressure (SBP) <140 mmHg reduce the risk of death or severe disability compared with guideline-recommend treatment with target SBP <180 mmHg.

Trial Data

 * Design
 * Multicenter, open label randomization, blinded assessment of outcome
 * N = 1,000 (500 to intervention, 500 to control)
 * Setting: 173 hospitals in 7 countries
 * Enrollment: 2011-2016
 * Primary Outcome: Death or major disability (score of 4-6 on modified Rankin scale (mRS) at 90 days after randomization)
 * Notable inclusion criteria: Age >18 with spontaneous IPH and SBP >180 mmHg on arrival, able to be treated within 4.5 hours, IPH volume <60 mLm Glasgow Coma Score ≥5.
 * Notable exclusion criteria: infratentorial IPH, known underlying lesion to cause IPH, significant IVH
 * Groups:
 * Intensive: SBP <140 mmHg using IV nicardipine exclusively
 * Standard: SBP 140-180 mmHg
 * Results:
 * Death or major disability in 38.7% (intensive) vs 37.7% (standard) (LR 1.04, 95% CI 0.85-1.27, p=0.72)
 * Trend towards less hematoma expansion of >33% in intensive group (18.9% intensive vs 24.4% standard, LR 0.78, 95% CI 0.58-1.03, p=0.08)
 * Safety:
 * Treatment-related serious adverse events within 72 hours: no difference at all
 * Trend towards increase in neurological deterioration in intensive group (11% intensive vs 8% standard, LR 1.39, 95% CI 0.92-2.09, p=0.11)
 * Any serious adverse event within 3 months: 25.6% (intensive) vs. 20% (standard) (LR 1.30, 95% CI 1.00-1.69, p=0.05)
 * Any renal adverse events within 7 days: 9% intensive) vs 4% (standard) (LR 2.32, 95% CI 1.37-3.94, p=0.0018)

Major Points

 * This trial showed no evidence of benefit for intensive treatment with a trend towards more neurological deterioration, significantly more renal adverse events within 7 days, and borderline significantly more serious adverse events within 3 months.
 * Common interpretation of this trial after completion was that goal SBP <140 mmHg is of no benefit and may cause harm, which is contradictory to the results of the similarly-designed INTERACT2 trial. This is not reflected in the 2015 American Heart Association / American Stroke Association Guidelines for Management of Spontaneous Intracerebral Hemorrhage, because these were published prior to the results of this trial.
 * Analysis of SBP obtained in this trial (Figure 1) shows that the average SBP actually achieved in the intensive group was ~120-130 mmHg, while in the standard group it was 140-150 mmHg. Thus the intensive group blood pressures were lower than the planned goal of <140 mmHg, while the standard group blood pressures were lower than the planned goal of <180 mmHg. As such, this trial actually suggests that, if anything, SBPs in the 120s had a trend to harm and no benefit compared with SBPs in the 140s.
 * As INTERACT2 suggested that SBPs in the 130s-140s range has a trend to improve outcomes compared with 150s-160s, while ATACH-2 suggested that SBPs in the 120s had worsened outcomes compared with 140s, a reasonable interpretation is that 120s is too low, 130s-140s are probably okay, and SBPs in the 150s-160s may be too high. Taking the two trials together, we therefore aim for SBP 130-150 mmHg in most situations.