WSC 2025 | ATACH-2: the association between hourly systolic blood pressure variability and outcomes in ICH

The Antihypertensive Treatment of Acute Cerebral Hemorrhage-2 trial, the primary goal of that trial was whether intensive systolic blood pressure reduction in patients with intracerebral hemorrhage is superior to standard systolic blood pressure reduction. So there were, the patients were randomized into two arms. So if you had an intracerebral hemorrhage, you had a high blood pressure or systolic blood pressure of 180 millimeters or greater, you were randomized. So you were actually randomized to intensive systolic blood pressure reduction and standard systolic blood pressure reduction. So in one arm, using intravenous nicardipine, the goal was to reduce your systolic blood pressure to less than 140 mm of mercury for the next 24 hours. In the other arm, it was less than 180 mm of systolic blood pressure for the next 24 hours. And the premise was why intensive blood pressure reduction would be beneficial was because in intracerebral hemorrhage, what we have learned is that patients who come in with intracerebral hemorrhage, they actually have an expansion of the hemorrhage. So intracerebral hemorrhage is not a monophasic disease. In fact, it’s a progressive disease for the first few hours. So the hematoma actually continues to grow. And as the hematoma actually grows in size, it causes more neurological injury and increases the chance of death or disability. So if you lower blood pressure, you actually may reduce the expansion of hematoma. And that subsequently would lead to a lower risk of death or disability in patients with intracerebral hemorrhage. So the primary trial showed no difference. So whether you were randomized to the intensive systolic blood pressure reduction or you were randomized to the standard systolic blood pressure reduction, your chance of death and disability was no different. There was a lower risk of hematoma expansion in the group that was randomized to the intensive systolic blood pressure reduction, but that didn’t really change the rate of death or disability. And the other thing that was found was the patients who got intensive systolic blood pressure reduction actually had a higher risk of kidney problems, so acute kidney injury, because the kidney blood flow was also altered in these patients with chronic kidney disease because of high blood pressure for a long period of time. So since then, people have tried to look for other parameters that may actually explain, beyond just blood pressure reduction, that may actually explain the death and disability in these patients and perhaps maybe a new therapeutic target. So blood pressure change. So essentially, blood pressure fluctuation has actually emerged as another parameter. So, you know, for many years, it was just the absolute blood pressure value. So we looked at the absolute blood pressure value and used that as a predictor for death or disability or hematoma expansion and used that as a therapeutic target that if you reduce the blood pressure to a certain value, that should give you the therapeutic benefit. But obviously, that has not panned out. So then, you know, we have shifted to actually other parameters like blood pressure fluctuation. And it seemed like patients with intracerebral hemorrhage who have higher blood pressure fluctuation. So basically the values are moving up and down in the first 24 hours are at higher risk for death or disability. So we actually tested this hypothesis that does blood pressure fluctuation mean more in the early hours as compared to the later hours. So we took the ATACH-2 data. We had all the blood pressure recordings. For every patient, we had blood pressure, the highest blood pressure and the lowest systolic blood pressure for every hour up to 24 hours. So these patients were actually treated within 4.5 hours of symptom onset, and then we collected all this blood pressure recording. So then we actually looked at the blood pressure fluctuation per every hour so blood pressure fluctuation hour one hour two all the way to hour 24 and looked at their effect on outcome so three-month outcome. So essentially you can tell that there is a difference so patients who have higher rate of death or disability or those who actually have death or disability seem to have more fluctuation in blood pressure as compared to those who don’t have death or disability at three months after the randomization in the study. And it’s interesting that the difference in fluctuation is really very early on. So it’s really in the first eight hours, the fluctuation really seems to make a difference on outcome. So afterward, the fluctuation doesn’t seem to have a big effect on death or disability and other parameters in intracerebral hemorrhage. So we actually looked at hematoma expansion, we looked at neurological deterioration, so worsening of neurological deficits after being in the study or randomized in the study. And there seems to be a consistent pattern that blood pressure fluctuation really makes a difference when it’s in the first eight hours, and after that, it really doesn’t have much of an effect on patients’ outcomes. So what it does is it actually creates a time vulnerability, something that was not described before. So there was always an understanding that, you know, blood pressure fluctuation or blood pressure variation, whatever terminology we use, was actually a detrimental thing. And new therapeutic agents, instead of purely focusing on blood pressure reduction, should also focus on reduction in the fluctuation. So I think that this study adds a higher level of evidence to that particular thought. It also creates a time window. So if you really want to make a difference by reducing blood pressure fluctuation, you have to actually treat that blood pressure fluctuation in the first eight hours. So there is almost a time window when it comes down to actually taking away the negative effect of blood pressure fluctuation. So I think that was the other study and what we found from that study. And, you know, I think it’s interesting to mention that, you know, for many years, not just in stroke or neurological diseases, even if you look at the first historical description of blood pressure, it talked about two particular parameters. It talked about the absolute value, and it talked about the fluctuation in blood pressure. And since in the last 300 years, all the focus had been on the absolute value of blood pressure, and somehow that initial message was lost. And now we’re actually regenerating that message and trying to actually define another variable that actually has a potential impact on patient outcomes.

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