INTERACT-2: should blood pressure be aggressively lowered acutely after intracerebral hemorrhage?

B lood pressure (BP) lowering after spontaneous intra-cerebral hemorrhage (ICH) is intuitively attractive as a means to prevent continued bleeding or perihematomal edema. Concerns about potential reduction of cerebral perfu-sion pressure with concomitant risk of ischemia, particularly among patients with a recalibrated autoregulatory curve as a consequence of chronic hypertension, were largely mitigated by imaging studies that found no significant reduction of cere-bral blood flow in the face of pharmacological BP lowering, 1–3 and the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) pilot study. 4 The INTERACT investigators have now formally put the concept to test and have shown that if there is a clinical effect of BP lowering, it is fairly muted and smaller than anticipated. Of 2794 patients with spontaneous ICH, the relative risk for poor outcome was 0.94 (0.87–1.002), P=0.063, in the intensive BP-lowering group (to target systolic pressure ≤140 mm Hg) compared with the control guideline group aiming for systolic pressure ≤180 mm Hg. Various permutations of modified Rankin Scale dichotomization were also nonsig-nificant when adjusted for baseline factors. The Rankin shift analysis using ordinal logistic regression was marginally significant in favor of the intensive BP-lowering group (P=0.04). Importantly, no differences in mortality and major safety events, including neurological worsening, were observed. 1 perihematomal isch-emia does not develop and, with the absence of any neu-rological complications with aggressive BP lowering in INTERACT-2, 5 offers further assurance of the safety of acute BP treatment. Hematoma expansion has been postulated to be the mechanism of worsening after acute ICH and the principal mechanism by which aggressive early BP lowering might act. In the pilot INTERACT, BP lowering was associated with attenuation of hematoma growth by a small margin. 6 But in INTERACT-2, 5 BP reduction was not associated with any change in hema-toma volumes among the subgroup of patients who underwent repeated computed tomographic scanning at 24 hours. Possibly, this was because many of these hematomas were already stable ; treatment occurred at a median of just 4 hours from onset, although subgroup analysis found no heterogeneity between those randomized <4 hours and ≥4 hours. Furthermore, the average hematoma volumes were small at 11 mL; small hema-tomas show the smallest relative growth, and so it is possible that many of these patients were not prone to progressive hema-toma enlargement and clinical deterioration over hours. The lack of a biological substrate for the mechanism of clinical …