Intensive Blood Pressure Reduction Linked to More Neurological Deterioration

Adnan I. Qureshi, MD

Newly published study data from a post hoc analysis of a randomized clinical trial, ATACH-II (NCT01176565), suggest that caution should be taken against the generalization of recommendations for the intensive reduction of systolic blood pressure (SBP).¹

Ultimately, the investigators identified a higher rate of neurological deterioration within 24 hours in patients with intracerebral hemorrhage (ICH) and initial SBP of ≥220 mmHg who did not receive any benefit in reducing hematoma expansion at 24 hours, nor death or severe disability at 90 days. The results showed that among the 228 individuals with SBP levels in that range, the rate of neurological deterioration within 24 hours was 15.5% for those who underwent intensive reduction compared to 6.8% for those treated with a standard approach (relative risk, 2.28; 95% CI, 1.03–5.07; P = .04).

The analysis was performed by Adnan I. Qureshi, MD, professor of clinical neurology, University of Missouri Health Care, and colleagues, in November 2019 on data from the multicenter randomized clinical trial (conducted from May 2011 to September 2015). Patients with ICH and initial systolic blood pressure of ≥180 mmHg, randomized within 4.5 hours after symptom onset, were included, with intravenous (IV) nicardipine infusion titrated to goals as the intervention.

“There’s always been concern that if your starting blood pressure is very high and you’re undergoing intensive SBP reduction…whether there is a provocation of cerebral ischemia or provocation of another cerebral event from such a dramatic change and [if] neurological deterioration is actually a manifestation of such a change,” Qureshi told JAMA Neurology.² “As suspected, what we saw is that when you’re reducing blood pressure, or particularly [with] intensive systolic blood pressure reduction, which is a large drop in blood pressure, you’re seeing that these patients have a higher rate of neurological deterioration. So, it does actually support that perhaps the brain is unable to tolerate such a dramatic change or reduction in blood pressure.”

Additionally, the rate of death and severe disability was 39% for those who underwent the intensive approach compared to 38.4% for those in the standard group (relative risk, 1.02; 95% CI, 0.73–1.78; P = .92), which was not significantly different between the 2 groups. Hematoma expansion within 24 hours was 13.8% and 15.8% for intensive and standard SBP reductions, respectively (relative risk, 0.87; 95% CI, 0.46–1.64; P = .67) which was not significantly different.

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Although, there was a significantly higher rate of kidney adverse events (AEs) in those randomized to intensive SBP reduction (13.6%) compared to the standard care group (4.2%) for a relative risk of 3.22 (95% CI, 1.21–8.56; P = .01). There was no difference observed in the rate of kidney serious AEs. The percentage of participants with treatment-associated serious AEs within 72 hours after randomization was 2.7% and 0.8% in the intensive and standard SBP reduction groups, respectively (relative risk, 3.22; 95% CI, 0.34–30.48; P = .35), while he percentage of serious AEs during the full study duration was 27.3% and 17.8%, respectively (relative risk, 1.53; 95% CI, 0.94–2.51; P = .09).

In total, 8532 patients were screened and 999 individuals with a mean age of 62.0 years (standard deviation [SD], 13.1; 620 men [62.0%]) underwent randomization and had an initial SBP value. The SBP goal for the intensive group was 110–139 mmHg while the standard group’s SBP goal was 140–179 mmHg.

“As we’re all aware, the AHA/ASA guidelines, when it comes down to the management of blood pressure in acute ICH, specified that for patients who have initial SBP that’s greater that 150 mmHg but less than 220 mmHg, there is a strong recommendation that blood pressure reduction should be undertaken and may actually be beneficial,” Qureshi told JAMA Neurology. “However, if patients have initial blood pressure more than 220 mmHg, then the guidelines actually become more obscure because there just is not enough data to support any recommendation.”

In an accompanying editorial, Matthew B. Maas, MD, MS, of the Department of Neurology at Northwestern University, noted that evidence does suggest that early reduction of SBP may confer more benefit to the patient and that 2 specific—and complementary—pathways exist that could demonstrate such a benefit in a clinical trial.³

“One path is to integrate the findings of these numerous secondary trial analyses and observational studies to inform the design of stricter and therefore more optimal inclusion criteria and intervention protocols, focusing on patients with low to moderate severity ICH and moderately elevated initial blood pressures and effectuating a very early and sustained reduction in SBP,” he wrote, noting that this subgrouping approach is relatively crude, though. The other path, Maas wrote, would include methods that personalize treatment according to individual patient’s physiology through the estimation of that individual’s autoregulatory capacity boundaries and their susceptibility to ischemic injuries or complications.

REFERENCES
1. Qureshi AI, Huang W, Lobanova I, et al. Outcomes of Intensive Systolic Blood Pressure Reduction in Patients With Intracerebral Hemorrhage and Excessively High Initial Systolic Blood Pressure: Post Hoc Analysis of a Randomized Clinical Trial. JAMA Neurol. Published online September 8, 2020. doi:10.1001/jamaneurol.2020.3075
2. Intensive Systolic Blood Pressure Reduction in Intracerebral Hemorrhage. JAMA Neurology. Author interview. Published September 8, 2020. Accessed September 29, 2020.
3. Maas MB. Intensive Blood Pressure Reduction in Patients With Intracerebral Hemorrhage and Extreme Initial Hypertension: Primum Non Nocere. JAMA Neurol. Published online September 8, 2020. doi:10.1001/jamaneurol.2020.3081