Is Intensive Blood Pressure Lowering Beneficial in Acute Intracerebral Hemorrhage ?

Seemant Chaturvedi, MD reviewing Anderson CS et al. N Engl J Med 2013 May 29. Equivocal outcomes from the INTERACT 2 trial The INTERACT 1 trial (JW Neurol Aug 14 2012) gave preliminary evidence that early, intensive blood pressure lowering might improve intracerebral hemorrhage (ICH) outcomes. Now, researchers report the findings of INTERACT 2. They enrolled patients with acute, spontaneous ICH whose blood pressure could be treated within 6 hours of symptom onset and lacked an overt structural cause, who were not in deep coma and not scheduled for immediate surgery. Patients were randomized to an intensive systolic blood pressure (SBP) target of <140 mm Hg within 1 hour of randomization, maintained for 7 days, or a conventional, guideline-determined SBP target of <180 mm Hg. The primary outcome was death or major disability at 90 days. A secondary analysis assessed improvement across the range of functional outcomes on the modified Rankin scale (ordinal analysis). Among 2794 patients with 90-day outcome data (mean age, 63.5; 63% male; average blood pressure at enrollment, 179/101 mm Hg; 83.5% with deep ICH; 28.4% with intraventricular extension), the mean SBP at 6 hours after randomization was 139 mm Hg with intensive therapy versus 153 mm Hg with conventional treatment. The primary outcome was not significantly different between treatments (52.0% with intensive therapy, 55.6% with conventional therapy; odds ratio, 0.87; P=0.06). In the ordinal analysis, the odds of disability were a significant 13% lower with intensive than with conventional treatment. Death or major disability at 7 days and 28 days did not differ between groups. In a subgroup of patients with repeat imaging at 24 hours, hematoma growth did not differ between the two treatments. Comment In this large-scale trial, the primary outcome missed statistical significance, but there was a trend for improved outcomes, and functional outcomes showed a benefit with intensive blood pressure lowering. The authors achieved their blood pressure target of a 13 mm Hg reduction in systolic blood pressure, but the absolute difference in death and major disability was only 3.6%, not 7.0% as hypothesized, raising questions about whether the patients had too many preexisiting comorbidities or whether the earlier, pilot data were overly optimistic. The greater rate of care withdrawal with intensive versus conventional therapy (5.4% vs. 3.3%) and unreported differences in posthospitalization rehabilitation may have slightly diminished a potential treatment effect. For now, intensive lowering of blood pressure in acute intracerebral hemorrhage appears to be unharmful and may lead to a clinical benefit. Editor Disclosures at Time of Publication Citation(s): Anderson CS et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med 2013 May 29; [e-pub ahead of print]. (http://dx.doi.org/10.1056/NEJMoa1214609)