NeuroVoices: Chitra Venkatasubramanian, MBBS, MD, MSc, FNCS, on Debating Optimal Blood Pressure Targets After Intracerebral Hemorrhage

Chitra Venkatasubramanian, MBBS, MD, MSc, FNCS

(Credit: Stanford University)

In the previous randomized ATACH-2 trial (NCT01176565), researchers compared intensive versus standard systolic blood pressure (BP) targets in patients with intracerebral hemorrhage (ICH) to determine whether tighter BP control could improve outcomes.¹ Coming into the study, eligible patients had hemorrhage volumes under 60 cm³ and a Glasgow Coma Scale score of at least 5. Then, participants were assigned to either an intensive BP target of 110–139 mm Hg or a standard target of 140–179 mm Hg, using intravenous nicardipine within 4.5 hours of symptom onset. The primary outcome measured was death or major disability at 3 months.

The trial, which enrolled 1000 patients, was stopped early because of futility. At 3 months, death or disability occurred in 38.7% of the intensive-treatment group versus 37.7% of the standard-treatment group, showing no significant difference in outcomes. Although treatment-related serious adverse events were rare, the intensive-treatment group had a significantly higher rate of renal complications in 7 days. The findings suggested that more aggressive systolic BP lowering does not improve functional outcomes in ICH and may increase the risk of renal injury. Despite these findings, discussions around optimal BP targets in ICH continue to evolve.

At the 2025 American Academy of Neurology (AAN) Annual Meeting, held April 5-9, in San Diego, California, Chitra Venkatasubramanian, MBBS, MD, MSc, FNCS, clinical professor of stroke neurology and neurocritical care at Stanford University, participated in a debate on BP targets in ICH.² In a new iteration of NeuroVoices, Venkat noted key findings from trials like ATACH-2, emphasizing that early intervention, particularly in younger patients without chronic hypertension, may be critical for efficacy. Venkat also talked about how imaging studies have not demonstrated ischemia resulting from intensive BP lowering, reinforcing the safety and clinical value of early, targeted management strategies in ICH care.

NeurologyLive: Could you provide an overview of the AAN debate and what you presented on your side?

Chitra Venkatasubramanian, MBBS, MD, MSc, FNCS: I was debating, along with my neuro ICU colleague from New York, Kara R. Melmed, MD. We were debating this particular issue about BP lowering after brain hemorrhage—how low can we go, and should we go low? I was debating the pro position, saying yes, we should go low, and she was debating the position that you shouldn't go too low. We had a ball of a time debating it [that] morning.

Brain hemorrhage is something that I'm extremely passionate about. I've been working in this field for over 2 decades now, and I've seen the field move from being a condition associated with a lot of nihilism—where once you have a brain hemorrhage, people say, "Oh my god, we can't really improve your outcomes"—to a place where we now say, "Yes, we can improve outcomes," and here are some strategies, tools, and ways to do it. So, it's been very exciting to watch this journey over 20 years.

Going into the debate and your side—what evidence supports lowering BP in ICH, and how does that impact patient outcomes?

If I may take a step back—once you have a brain hemorrhage, what we know physiologically happens is that at least a third of patients will have expansion of the bleed in the brain. So it's not a one-time event—it continues to accrue and grow, and it happens pretty fast in the first 2 to 3 hours for those who are going to expand.

We can categorize patients into those who expand a lot, those who expand a little, and those who don't really expand. Any therapy that we provide upfront is going to have what I call the most bang for the buck. Elevated BP is associated with hematoma expansion, hence the movement toward lowering the BP. The goal is to push the field forward and see how low we can actually go to provide the most benefit for our patients by limiting the amount of hemorrhage that expands.

You asked me about the data and literature—there were 2 very big randomized trials done for BP lowering: one was called INTERACT-2, and the other was ATACH-2. Both of them looked at 2 different BP targets. In INTERACT-2, the lowest patients got was about 130, and in ATACH-2, patients got to the low 130s. Even though those 2 trials were not significant for their primary end points—and there are a lot of reasons why they weren’t—when those 2 numbers were pooled together to create a much larger meta-analysis, it was very clear that you can very safely lower BP beyond what is currently advocated.

So that was the evidence I was able to dissect and present to the audience [during the debate]. The key reason these 2 trials didn’t meet their primary end points was that the therapy for BP lowering was started late—after the hematoma had already expanded. So, you couldn’t really see a signal on hematoma expansion. But when you look at the overall population, especially those patients where you have early BP lowering, you can definitely see an improvement in outcomes and a decrease in hematoma expansion. So that’s the data I presented [that] morning to make my case that, yes, you should go low—and you can go low.

Were there any other specific patient populations or clinical scenarios where a lower BP target may be particularly beneficial?

Yeah, that’s a fantastic question. The particular patient populations that can really benefit from a lower BP target would be those who don’t come in with a prior history of significant hypertension.

So let’s say you have a younger patient who’s coming in with a bleed, and they arrive really fast—in 30 minutes to an hour of symptom onset. In those patients, we can lower BP very intensely, very aggressively, without any concerns. Patients who come in during that early time period again stand to benefit the most from BP lowering.

It’s not to say that you can’t lower BP after 2 or 3 hours—you should still do it—but you need to get there fast and, most importantly, minimize fluctuations and variability, because that’s also been associated with worse outcomes. So if you want to talk about a group of patients most likely to benefit from intensive or aggressive BP lowering, it would be patients who come in very early after symptom onset—especially younger patients.

How do you potentially address concerns such as systemic injury or cerebral perfusion when advocating for lower BP targets in ICH?

This has been an eternal debate, I would say—balancing the perceived risks and benefits of BP lowering. The perceived risks are that the majority of patients who have brain hemorrhages are those with a history of diagnosed or undiagnosed hypertension.

In those patients, what we call the autoregulation curve is right-shifted. So when we drop BP their brains aren’t used to seeing low BP, and the concern is that we’re creating an ischemic environment through the therapies we’re using. This has been looked at in a variety of ways—with PET scans, CT perfusions, and MRI perfusion studies.

I would say that for the majority of patients who come in with small to moderate-sized hemorrhages, there is no evidence of brain ischemia around the hemorrhage. What we see around the hemorrhage is what I like to call hibernating tissue. It’s not ischemic tissue—it’s just less metabolically active hibernating tissue. By intensely lowering BP, we don’t seem to be harming these patients. At my center, we also did repeated MRI assessments to see whether we were creating brain ischemia—positive diffusion-weighted imaging lesions that show up. The only association we found was with the size of the hemorrhage, not with the BP lowering.

So I would say the controversy has tilted toward: no, we are not creating brain ischemia. But if you miss the window, you’re going to let the hemorrhage expand. So I think the pendulum has swung over to—it’s safe to lower it.

Transcript edited for clarity. Click here for more coverage of AAN 2025.

REFERENCES
1. Qureshi AI, Palesch YY, Barsan WG, et al. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. N Engl J Med. 2016;375(11):1033-1043. doi:10.1056/NEJMoa1603460
2. Venkatasubramanian C. Yes: Blood Pressure Targets in ICH: Should We Go Low?. Presented at: 2025 AAN Annual Meeting; April 5-9; San Diego, CA. Controversies in Neurology Plenary Session.

Editor’s Note: Venkatasubramanian has disclosed that she has received personal compensation for serving as a Consultant for Ceribell and as an Expert Witness for McKeen and associates. She also has noted that she has stock in Ceribell. In addition, Venkatasubramanian has received research support from Bard Inc., Biogen, and NIH.