WSC 2025 | Triple therapy for the prevention of recurrent intracerebral disease events: results from TRIDENT

So we’ve known for a very long time that blood pressure elevation is very important in the risk of intracerebral hemorrhage. Of all the types of cardiovascular disease there’s a much steeper relationship between levels of blood pressure and the incidence of intracerebral hemorrhage and therefore a reduction in blood pressure of a comparable amount across different cardiovascular diseases offers a bigger effect in patients with intracerebral hemorrhage. But this is observational data or secondary analysis of clinical trials. We’ve never had direct evidence of the benefits of more intensive blood pressure lowering in intracerebral hemorrhage. And on top of that, it’s very challenging to control blood pressure in clinical practice in the community and after having an intracerebral hemorrhage. So the purpose with TRIDENY was to solve two issues. First of all get the direct evidence of the benefit of more intensive blood pressure lowering below 130 systolic in this very high risk patient group and offer a simple strategy that can achieve this in clinical practice. So a triple pill of 20 milligrams of telmisartan, 5 milligrams of amlodipine, and 1.25 milligrams of indapamide provides most of the efficacy of a full dose, much less harm, so better tolerability, and provides a quicker response to blood pressure lowering. And there’s been other data to show that that works much better than routine care. So we put them together in a large trial, placebo-controlled. We had an active run-in phase over two weeks to ensure that the patients who were randomized showed good tolerability to the drug and levels of adherence and we followed up a cohort of almost 1,700 patients over an average period of three years. We showed the treatment was very safe, the blood pressure control was very stable in the triple pill group, achieving on average a level of 127 millimeters systolic compared to 138 in the placebo group. And this was on top of background therapy in a well-managed patient group. Overall, for the primary endpoint of recurrent stroke of any type, there was an almost 40% reduction in the risk, what we call a hazard ratio of 0.61, and that was highly significant and clearly important. That effect on recurrent stroke was driven by the prevention of recurrent intracerebral hemorrhage where the treatment effect was a massive 60% avoidance. And in fact, if you look at the incidence rate curves, it was almost flat in the triple pill group compared to the control group. Across the other secondary points of myocardial infarction, stroke and cardiovascular death, comparable 40% reduction, and we showed very good levels of blood pressure control, good levels of tolerability. There was a slight increase in creatinine and estimated glomerular filtration rate. Much of that is just a normal response to the kidneys having a shift in their blood flow from more intensive treatment and nothing really to worry about. But we have to explore that in a little bit more detail. The triple pill drug is not widely available on the market yet. It’s maybe 12 months away and it gives us a very exciting opportunity to prove that blood pressure control is just so important in patients who’ve had an intracerebral hemorrhage.

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