Is BP Lowering During Acute Intracerebral Hemorrhage Safe?

Abstract

One of the most devastating consequences of hypertension is stroke resulting from brain hemorrhage. These acute situations generate some of the highest blood pressure (BP) readings. Despite impressive levels of BP, we are often reluctant to treat these patients with BPlowering drugs for three reasons. First is the concern that the area around the hemorrhage, called the penumbra, is in jeopardy of ischemia, and BP reduction might tip it more towards ischemia and extend the consequences of the stroke. Second, thrombolytic therapy, which requires a systolic BP <185 mm Hg to be given safely, is not an issue since that would worsen this presentation. Finally, there simply wasn’t evidence to demonstrate benefit in this situation until recently, when the pilot study Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT), which assessed the effectiveness of early intensive BP-lowering targeting lower systolic BP (SBP) levels of <140 mm Hg in patients with acute intracerebral hemorrhage (ICH), showed less growth in the size of the brain hematoma at 72 hours in patients assigned to a lower (<140 mm Hg) compared with a higher (<180 mm Hg) in-hospital BP goal. Building on this original study, the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 (INTERACT2) was recently conducted. INTERACT2 was a large multicenter international prospective randomized open treatment trial. Patients with spontaneous acute ICH within the previous 6 hours were randomized to receive either intensive treatment to lower BP to a target SBP of <140 mm Hg within 1 hour vs guideline-recommended treatment of SBP <180 mm Hg. The BP level was maintained for the next 7 days after randomization. The agents used to lower BP were left to the discretion of the treating physician. The main outcome at 90 days was death or major disability using a Rankin scale, where a score of 0 indicates no symptoms/disabilities, 5 indicates severe disability, and 6 indicates death. A prespecified ordinal analysis of a modified Rankin score was also performed. The analysis showed a 13% improvement in the modified Rankin score with intensive treatment (odds ratio for greater disability, 0.87; 95% confidence interval, 0.77–1.00; P=.04). Rate of 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. Episodes of severe hypotension were similar in both groups and occurred in <1% of participants. The difference in hematoma growth between groups was not significant. What this says to us is that (1) it appears to be safe to lower the systolic BP within about 6 hours of an ICH, and (2) there may be a small benefit to doing so in terms of symptoms and disabilities following stroke, bearing in mind that many (two thirds) of the participants were Chinese and that the main drug used was urapidil (an a1 adrenoceptor and serotonin blocker), which is not available in the United States. It will be important to frame INTERACT2 findings in the light of the ongoing trial being conducted in the United States—Antihypertensive Treatment of Acute Cerebral Hemorrhage Trial II (ATACH)—which will compare treating the SBP to <140 mm Hg vs <180 mm Hg in patients with acute ICH using nicardipine as the agent of choice to lower BP. Some patience will be needed as the results are expected in 2016. In the meantime, there is some encouragement that managing high systolic pressures in the presence of an acute brain hemorrhage does not cause harm and may have some benefit.