Whether rapid lowering of elevated blood pressure would improve the outcome in patients with intracerebral hemorrhage is not known.
We randomly assigned 2839 patients who had had a spontaneous intracerebral hemorrhage within the previous 6 hours and who had elevated systolic blood pressure to receive intensive treatment to lower their blood pressure (with a target systolic level of <140 mm Hg within 1 hour) or guideline-recommended treatment (with a target systolic level of <180 mm Hg) with the use of agents of the physician’s choosing. The primary outcome was death or major disability, which was defined as a score of 3 to 6 on the modified Rankin scale (in which a score of 0 indicates no symptoms, a score of 5 indicates severe disability, and a score of 6 indicates death) at 90 days. A prespecified ordinal analysis of the modified Rankin score was also performed. The rate of serious adverse events was compared between the two groups.
Among the 2794 participants for whom the primary outcome could be determined, 719 of 1382 participants (52.0%) receiving intensive treatment, as compared with 785 of 1412 (55.6%) receiving guideline-recommended treatment, had a primary outcome event (odds ratio with intensive treatment, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P=0.06). The ordinal analysis showed significantly lower modified Rankin scores with intensive treatment (odds ratio for greater disability, 0.87; 95% CI, 0.77 to 1.00; P=0.04). Mortality was 11.9% in the group receiving intensive treatment and 12.0% in the group receiving guideline-recommended treatment. Nonfatal serious adverse events occurred in 23.3% and 23.6% of the patients in the two groups, respectively.
In patients with intracerebral hemorrhage, intensive lowering of blood pressure did not result in a significant reduction in the rate of the primary outcome of death or severe disability. An ordinal analysis of modified Rankin scores indicated improved functional outcomes with intensive lowering of blood pressure.
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.
Source: Journal Watch Neurology