Neurologic Worsening Seen with Intensive BP Lowering After Intracerebral Hemorrhage

Patients in a single tertiary care facility who were hospitalized for primary intracerebral hemorrhage (ICH) and managed with a systolic blood pressure (SBP) target of less than 140 mm Hg developed more acute cerebral ischemia on MRI and neurologic deterioration than patients whose SBP goal was less than 160 mm Hg.

So finds a retrospective study with a historical controls recently published online in Neurology.

“Although high blood pressure puts a patient at risk for hemorrhagic stroke, lowering blood pressure too much right afterwards makes matters worse,” says stroke neurologist Ken Uchino, MD, Director of Research and Education in Cleveland Clinic’s Cerebrovascular Center and a senior author of the study. “This study adds to the evidence that we should not be too aggressive with lowering blood pressure following an intracerebral hemorrhage.”

Study design

The study reviewed records of 286 consecutive patients with acute primary ICH admitted to Cleveland Clinic during 2013 and 2014. In 2013, the institutional protocol was an SBP target of less than 160 mm Hg; in 2014, the target was reduced to below 140 mm Hg.

According to Dr. Uchino, the change in targets was prompted by the INTERACT2 trial, published in the New England Journal of Medicine (2013;368:2355-2365), which found that early intensive blood pressure lowering (within six hours of ICH onset) resulted in better functional outcomes. Notably different from the clinical trial, the lower blood pressure target was applied to all patients with acute ICH, regardless of time since hemorrhage onset.

To qualify for the current study, a brain MRI with diffusion-weighted imaging had to have been performed within two weeks of a patient’s admission. Those with ICH due to trauma, vascular malformations or tumors were excluded, as were patients who had emergent surgical evacuation or digital subtraction angiography prior to MRI, or if death or withdrawal of life support occurred within the first 72 hours. The inclusion criteria were met by 119 patients.

Patients were treated acutely with IV nicardipine, then chronically with oral medications within 24 to 72 hours of admission, to achieve the SBP targets. Nursing orders specified that the provider was to be notified for mean arterial pressures less than 65 mm Hg; no floor was specified for SBP levels.

The primary outcomes were the presence of acute cerebral ischemia on MRI and acute neurologic deterioration during hospitalization, defined as at least a 4-point increase in the NIH Stroke Scale. Two separate analyses were conducted, comparing:

• Patients with target SBP of less than 160 mm Hg (n = 62) versus those with target SBP of less than 140 mm Hg (n = 57)
• Patients with (n = 28) versus without (n = 91) acute cerebral ischemia evident on MRI

Study results

Compared with patients with the higher target SBP, patients with the lower target (< 140 mm Hg) had:

• A higher rate of cerebral ischemia (32 vs. 16 percent; P = .047)
• A higher rate of neurological deterioration (19 vs. 5 percent; P = .022)
• More days spent in the neurointensive care unit (median 3 days vs. 2 days; P = .014)
• More days spent in the hospital (median 7 days vs. 6 days; P = .02)

Analyzing the data from the perspective of who did or didn’t develop cerebral ischemia, no significant differences in SBP were found at admission, but patients with acute cerebral ischemia had significantly lower mean SBP over the subsequent 24 hours and lower minimum SBP over 72 hours. Having an SBP below 120 mm Hg was a significant predictor of acute cerebral ischemia.

What explains the findings?

According to Dr. Uchino, there were good theoretical reasons for thinking that intensive blood pressure lowering should be helpful during an acute hemorrhagic stroke — that is, to stop the bleeding. But these findings, as well as those of the ATACH-2 study (N Engl J Med. 2016;375:1033-1043), call that reasoning into question.

“For most patients, bleeding into the brain has probably stopped within a few hours of the onset of the stroke,” Dr. Uchino speculates. “After that point, too little blood pressure will more likely lead to poorer outcomes from ischemia.”

In search of the right balance

Dr. Uchino says that, as a result of this study, Cleveland Clinic has instituted two changes for treating patients hospitalized with an ICH:

• The SBP target has been raised back to less than 160 mm Hg.
• If SBP falls below 120 mm Hg, medications are immediately given to raise it.

He adds that while this is a retrospective study from a single institution, such analyses can reveal important information and reviewing outcomes in this way is an important part of quality assurance in healthcare.

“Almost any medical therapy has potential harm as well as benefits,” he says. “Studies like this one bring us closer to finding the right balance.”