ESOC 2024 | INTERACT4: blood pressure lowering in ambulance shows benefit in ICH but harm in ischemic stroke

There’s been at least two decades of work to try to understand whether early control of blood pressure will improve outcome from intracerebral hemorrhage. We’ve got borderline positive results but never anything definitive. A year ago we presented the INTERACT3 results that showed very clearly a positive outcome for intracerebral hemorrhage patients who receive a bundle of care which was driven by early intensive blood pressure control, but it still leaves a little bit of doubt in a care bundle what components drove the outcome. We haven’t really fully established that blood pressure control can reduce bleeding in the brain. So we embarked on the INTERACT4 trial to do very early (within 2 hours of the onset of symptoms) blood pressure control in patients with an acute stroke who were hypertensive in China. We had the hypothesis that because bleeding in the brain happens very quickly and is maximal in the first few hours that if we could control the blood pressure in that time period it would reduce bleeding and that would translate to improved clinical outcomes.

So the hypothesis for intracerebral hemorrhage was very strong and that’s what we tested and that’s what we proved. We thought that for those patients with acute ischemic stroke or cereal ischemia, we thought that it would be either safe or provide some marginal benefits. When a patient comes to hospital the guidelines recommend us to control blood pressure prior to giving thrombolysis and that takes maybe 15 minutes to draw up the intravenous antihypensive medication and control the blood pressure. If we could do it in the ambulance that may free up 15-20 minutes a time and there are some signals that getting the blood pressure under control after thrombolysis, we can reduce bleeding in the brain which is obviously a complication of thrombolysis. We did it without CTs. Patients who had an acute stroke within 2 hours of the onset of symptoms, were hypertensive, they had all other parameters which were highly positive towards acute stroke as opposed to a mimicking condition like a seizure or head injury or hypoglycemia.

We randomized over 2,000 patients to an intensive group or a very conservative group prior to presentation to hospital. The trial overall was neutral but the reason why it was neutral was there were divergent and balanced effects between patients with hemorrhage and patients with cerebra ischemia. It was actually harmful in those with cerebral ischemia, they had greater death and disability, but very beneficial in patients with intracerebral hemorrhage. I never imagined that just within a 20-30 minute ambulance ride from the home to the hospital, you’d get such an impressive treatment effect for people who are bleeding in the brain. So for the first time, we have a clear treatment that works for intracerebral hemorrhage. It’s now a matter of how do we get that treatment to the patients as quickly as possible, how can we diagnose intracerebral hemorrhage as quickly as possible in the ambulance? But if you have to have a 40 minute-1 hour ride to hospital and you’re bleeding in the brain that’s really bad news for you and if we get the blood pressure under control, that offers you a good chance of survival and surviving with less disability.

Final thing is, it’s rattled the cage in our guidelines that we’ve had for 30 years that says you’ve got to get the blood pressure under control before you give thrombolysis. Makes us wonder whether we’ve got that all wrong and that we’ve had some patients who’ve had adverse outcomes because we’ve been a bit too zealous with our approach to blood pressure lowering without any randomized supporting evidence which now we have available.

Well clearly there’s a lot of progress now with mobile stroke units where you put a standard CT scanner in a standard or purpose-built ambulance to allow the thrombolysis team to come to the patient and deliver thrombolysis therapy and that’s shown to be very beneficial. But these are very expensive to purchase and to maintain and the staffing, but clearly they work. You have two treatment now; patients who have an acute ischemic stroke the option is to give thrombolysis quickly now we have blood pressure control really firms that up, but mobile stroke units are not the answer. They’re too expensive. So there’s a lot of activity now to look at whether they can have some lightweight, more portable brain scanners, not just with a conventional radiation but other technology. We’re very close to having these devices freely available on the market. I think in the next couple of years there’ll be more mobile devices within the wards of the hospital. I think probably you’re looking at a 5-to-10-year horizon before we have these sort of lightweight caps that you can use in the ambulance. Then finally there’s a lot of interest in whether there’s some blood biomarkers that can pick up blood more readily in the first few hours and there’s a lot of activity going there. There are some scales that have been developed over the years looking at various clinical parameters. They’re not perfect, they could probably get an accuracy of maybe 70 or 80%. That’s probably not accurate enough to give us confidence. It’s all about having a firm diagnosis of bleeding in the brain with the lowest risk because we’ve shown harm if there’s ischemia and clear benefits if they’re bleeding, so it’s how can we get a tool that maximizes our positive prediction with the minimum of harm for the patient and I think probably if we can get things around 90% that’s probably a level that we’re going to be most comfortable with.