Chitra Venkatasubramanian

Good morning. I’m Dr Chitra Venkatasubramanian. I’m a clinical professor of stroke and neurocritical care at Stanford University.

Kara Melmed

And I’m Kara Melmed. I’m an associate clinical professor at NYU University.

Chitra Venkatasubramanian

And we are here at the American Academy of Neurology meeting in San Diego in 2025 with VJNeurology, and we are going to be discussing about a very hot topic that we debated yesterday at the plenary session, brain hemorrhage, blood pressure targets, how low can we go? So, Dr Melmed, what was your take on it?

Kara Melmed

I was arguing the point that we should not go too low. I was arguing for the fact that, well, we know with intracerebral hemorrhage, there’s always concern for hemorrhagic expansion and there’s concern for neurologic deterioration. And so we really want to prevent that and we can do that best in two ways, lowering blood pressure and reversing anticoagulation. So I was arguing that we shouldn’t lower it too low. I think that we need to stay within the most recent guidelines from 2022, the American Heart Association, American Stroke Association guidelines, 130 to 150. Rapid blood pressure lowering to 130 to 150 D is safe and it’s effective in improving outcomes.

Chitra Venkatasubramanian

Yeah, maybe we can also talk about a little bit about the background, about why we are lowering blood pressure in the first place, and maybe I’ll start with that. So once a brain hemorrhage happens, it’s not an instantaneous event, although it starts growing over the next two to three hours. So those are sort of the critical time periods in which any therapies that we do, whether it’s blood pressure lowering or anticoagulation reversal or any sort of care bundle that we put together is to be implemented. And anytime the hemorrhage volume increases, it worsens both mortality and increases the disability. It also increases the amount of edema that forms around the hemorrhage. So the effort is to corral all our efforts within those first two to three hours. And so I was taking the position that we have to go really fast and we have to go very low in terms of our blood pressure yesterday.

Kara Melmed

How low would you go, would you say? Yeah, so that’s a great question.

Chitra Venkatasubramanian

Currently, the American Heart Association guidelines in 2022, as you know, are from 130 to 150, lowering the systolic blood pressure to less than 140. My point was we can go even lower and we can do better in terms of improving our functional outcomes and decreasing mortality and do it in a very safe way.

Kara Melmed

We don’t have any randomized controlled trials that suggest that that would be safe. In fact, we know that there can be harm to the kidneys, there can be other harm to cerebral perfusion. So you really think we can go lower than 130?

Chitra Venkatasubramanian

I do, I do. And these are the reasons why I think we can go lower than 130 for the majority of patients. So in the two randomized trials, which were INTERACT-2 and ATACH-2, I mean, they were big trials for brain hemorrhage, but they weren’t like super big. So when we pooled together the data from both of these trials, it becomes fairly clear that you can safely lower to the lower end of the 130 to 150, which is 130, and even go lower to 120, which is what ATACH did. And the concern for renal adverse events, and so when we take a step back and look at what the definition of renal adverse events is, it’s a minimal bump in your creatinine to 0.3 milligrams per deciliter, which we see often happen in the intensive care unit, regardless of blood pressure lowering or not. It’s not that these patients got on dialysis or they had like permanent, you know, renal injury. So taking that into context, so that is the very minimal risk. And the bigger risk is not controlling the hematoma expansion, which, you know, is really going to set back the patient. So that’s where my point was coming in that, yes, we can go lower for the majority of patients safely, you know, and most of them are not going to have any sort of cardiac side effects or hypotension or renal side effects. But I would love to hear the flip side of the argument too.

Kara Melmed

So I think that both of these trials, there was no positive outcome looking at lowering blood pressure even below 130. There wasn’t any benefit in death or disability. There wasn’t any benefit in long-term outcomes. So I think we have to take that. These are the randomized control trials that we have. And we actually do have now a randomized control trial that does show benefit when we lower blood pressure rapidly. They didn’t go below 130. This is the INTERACT-3 trial that I’m talking about. Lowering blood pressure rapidly, bundled with aggressive glucose management, temperature management, and anticoagulation reversal that is fast and bundled, we do see a benefit. So even despite not going lower than 130, none of the patients in this trial went below 130. We see the benefit, and I think we need to use that data and use the data that we have to guide our management for these patients. Although many trials have shown that hematoma expansion is prevented with lowering the blood pressure, we’re just not seeing that manifest in clinical outcomes. And so we have to think about what’s actually important. Is it the hematoma expansion or is it the clinical outcome? Is it the radiographic finding of the hematoma expansion or is it actually how it impacts our patients?

Chitra Venkatasubramanian

Yeah, and I’m so glad you brought up the bundled care. So maybe we can pivot a little bit towards the bundled care. So in most of the conditions that we treat in the intensive care unit, it all comes around a bundle. So when we talk about sepsis or we talk about ARDS, and the same concept is for intracerebral hemorrhage as well, and we can call it code ICH, which just like we call code ischemic stroke, but code ICH. And the concept of this bundle, you know, has been floating around for quite some time from 2019, 2018 onwards. And it’s not really that there’s one component of the bundle that really improves the outcome. It is the whole package itself and getting a group of invested physicians, you know, to the bedside, right from the emergency room to the paramedics and implementing these four components of the bundle that you just talked about, blood pressure lowering. And sure, you can pick 140, you can pick 130, you can pick 120, but pick a target and get there fast. Because hematoma expansion is a physiological endpoint, but it’s really, that’s what’s going to drive your outcome in the end, because the larger your hematoma, the worse the outcome is going to be. So getting the blood pressure down, making sure that the temperature is controlled, making sure anticoagulation is reversed really quickly, and then glycemic control. And once you put together that package of code ICH or ICH alert, which I’m sure you’ve implemented in your hospital, we have implemented in our hospital as well, hopefully, fingers crossed, we will see much, much better outcomes for our patients. But maybe we can also talk about if you have a particular agent that you would like to use, and what if that particular agent is not available? And, you know, are there particular antihypertensive medications we can use and we shouldn’t use any thoughts on those?

Kara Melmed

Yeah, so I think that IV agents are obviously going to work faster. I don’t think the specific agent, I don’t think we have data to suggest that one agent is better than the other, but to underscore the point that you said, that it’s fast. We need to control blood pressure fast. And so obviously we can do that faster with IV agents, preferably a drip, a drip that we can have steady blood pressure control so we’re not just giving intermittent doses of IV pushes of antihypertensive drugs, but we want to treat these patients fast. And so with this Code ICH movement, with this idea that we need to be treating hemorrhagic stroke with as much thought and pressure and vigilance as we do ischemic stroke. And we know that we’re great at treating ischemic stroke in this country, and we can treat patients fast. Time is brain. We’ve got great door to needles in many of our hospitals. And so we need to see the same thing happening for our hemorrhagic stroke patients. And so having guidelines to say that we need to be treating blood pressure within 60 minutes from the door. We need to be treating anticoagulation reversal within 90 minutes from the door. Moving fast towards a target of getting these patients under control to, like you said, preventing the hematoma expansion and preventing, most importantly, the neurologic decompensation that we see for our patients that unfortunately with hemorrhagic stroke, there’s such a high mortality, there’s such a high morbidity that we really have an opportunity within those first one and two hours to really change the outcome and change the course for our patients. So choosing your agent, just be thinking about acting fast and then acting as stable as possible. So any IV drip I think would be my first go-to.

Chitra Venkatasubramanian

And I would completely agree with you. So if, you know, if a hospital doesn’t have intravenous infusions access, you know, there are parts of the world where they might not have. So what we would recommend is use whatever you have. But the key is get there fast, drop it and sustain it with as minimal fluctuations of variability as possible. And you and I collaborated on a publication looking at our practices in the United States, you know, about the early blood pressure reduction and achieving the target, whatever target was picked and that strategy even outside of a randomized control trial did show improvement in outcomes and that less number of patients were dying and less number of patients were getting into nursing homes and more number of patients were actually going home with better recovery so do you want to like talk a little bit about that as well?

Kara Melmed

We looked at ischemic stroke patients and hemorrhagic stroke patients across the United States at 11 hospital centers and we compared time to treatment for both groups so we know these are different patients. These are different presentations, but the aim was to show that if we can be fast with ischemic stroke patients, we should be just as fast with hemorrhagic stroke patients. Unfortunately, we did find significant difference in the way these patients were treated. There were similar, maybe door to CT times, but door to actual treatment times, door to reversal of anticoagulation was much longer in hemorrhagic stroke patients compared to door to thrombolytics or door to thrombectomy for ischemic stroke patients. And when we looked just at our ICH patients, we did find that there was an improved mortality. So less patients died on admission for the patients that had treat the patients that who had their blood pressure treated within 60 minutes had a less likelihood of dying on this hospital admission. So we know that treating the patients fast did impact outcomes and we know that it’s possible to do. So we’re looking forward to the publication of this manuscript soon so that we can share it with everyone and continue to push for this idea that we need to be acting quickly in hemorrhagic stroke patients.

Chitra Venkatasubramanian

And that brings about a point that these systems of care already exist in our hospitals because we have these systems of care for ischemic stroke patients. So we can utilize and we can harness the same systems of care to treat intracerebral hemorrhage with the same vigilance, with the same rapidity, and with the same urgency that we do ischemic stroke patients. And that reminds me, there was this recent trial, INTERACT-4, that looked at ultra-fast blood pressure lowering in the ambulance. So even before the paramedics knew whether it was, or the physicians knew whether it was an ischemic stroke or a hemorrhagic stroke, patients had their blood pressure rapidly lowered in the ambulance. It did not benefit ischemic stroke patients, but it immensely benefited the brain hemorrhage patients. There was a 25% reduction in death and severe disability with this very fast blood pressure lowering. So I think both of us agree that we should get there really fast and we should lower our blood pressure to whatever target we pick. And that’s the message that we want to send out to the viewers of this. So any final words?

Kara Melmed

I think I just want to say some final words about upcoming research and maybe where we’re going with blood pressure management. We know that every patient is different and we know that we need to treat every patient differently and we’re starting to learn more and more about precision medicine in ICH patients and in all of our neurologic patients. So starting to think about who is really going to benefit from the more aggressive blood pressure lowering. Obviously we know there’s some disadvantages to rapid blood pressure lowering despite the definitions of how bad the renal failure might be but there are definitely patients who would really benefit from much more aggressive blood pressure lowering to 120, 100 even. And so those are those early expanders. Those are the patients who are most likely to have hemorrhagic expansion. We have done many trials looking at how we can predict hemorrhagic expansion, but I think we’re moving into a place where we’re starting to see how we can use machine learning to really help us identify looking at the CT scan, looking at the patient characteristics, and really start to hone in on who is going to benefit the best and the most from rapid, aggressive blood pressure lowering. And I really hope to see our whole field moving in that direction and using the tools that we have available to us to, again, make the best outcomes for our patients.

Chitra Venkatasubramanian

And I’m very excited to continue to collaborate with you on how we can leverage machine learning and precision medicine to really individualize our blood pressure targets. So, you know, as few final words, intracerebral hemorrhage to be treated with the same urgency as ischemic stroke, having a care bundle and systems of care in our hospitals, and pick a target, be comfortable with the target, get there fast, and minimize the variability and stay on target. Yes. It was great debating with you yesterday.

Kara Melmed

So nice to see you again today as well.