Blood Pressure-Attained Analysis of ATACH 2 Trial

Study Questions:

In patients presenting with spontaneous intracerebral hemorrhage (ICH) with systolic blood pressure (SBP) ≥180 mm Hg, does rapid achievement of SBP <140 mm Hg lead to less death or disability at 3 months?

Methods:

This is a post-hoc analysis of ATACH 2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage), a large multicenter trial that randomized subjects with spontaneous ICH and SBP ≥180 mm Hg to either intensive SBP reduction (to 110-139 mm Hg) or standard SBP reduction (to 140-179 mm Hg), with treatment initiated within 4.5 hours of symptom onset. In this post-hoc analysis, subjects were grouped, regardless of randomization arm, as follows: 1) SBP <140 mm Hg not achieved within 2 hours of randomization (not reduced), and 2) SBP <140 mm Hg achieved within 2 hours of randomization (reduced). In subjects in whom SBP <140 mm Hg was achieved, subjects were further divided into: 3) SBP maintained <140 mm Hg for 21-22 hours (reduced and maintained), and 4) SBP ≥140 mm Hg for ≥2 hours between hour 2 and hour 24 (reduced and not maintained). The primary outcome was the proportion of patients with death or disability (defined as a modified Rankin scale [mRS] score of 4-6) at 3 months.

Results:

The not reduced (reference) group had 267 subjects. The reduced group had 731 subjects. Of those in the reduced group, 357 were considered reduced and maintained and 374 were considered reduced and not maintained. There was no significant difference in 3-month death or disability (mRS 4-6) between the reduced group and the not reduced group; between the reduced and maintained group and the not reduced group; and between the reduced and not maintained group and the not reduced group. Among secondary outcomes, there was no difference in hematoma expansion among the groups, but the rates of neurological deterioration within 24 hours were twice as high in the reduced and maintained group compared to the not reduced group (adjusted relative risk [aRR], 1.98; 95% confidence interval [CI], 1.08-3.62) and in the reduced and not maintained group compared to the not reduced group (aRR, 2.08; 95% CI, 1.15-3.75).

Conclusions:

There was no difference in 3-month death or disability in subjects whose SBP was lowered to <140 mm Hg within 2 hours and those whose SBP was not. A higher rate of neurological deterioration was observed in subjects with reduction with and without maintenance of SBP compared to those without SBP reduction.

Perspective:

Based on the results of a previous randomized controlled trial (INTERACT2), the 2015 American Heart Association/American Stroke Association guidelines recommend that for ICH patients presenting with SBP between 150 and 220 mm Hg without contraindication to acute BP treatment, acute lowering of SBP to 140 mm Hg is safe (Class I, Level of Evidence [LOE] A), and can be effective for improving functional outcomes (Class IIa; LOE B). Post-hoc analyses such as this one, and the adverse renal outcomes observed in the intensive treatment arm in the original ATACH 2 trial, will likely lead to a revision of these recommendations in future guideline statements.

Clinical Topics: Prevention, Hypertension

Keywords: Antihypertensive Agents, Blood Pressure, Cerebral Hemorrhage, Hematoma, Hypertension, Neurologic Manifestations, Primary Prevention, Risk, Stroke, Vascular Diseases


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