Breaking New Ground: Acoramidis Reduces AF Events in ATTR CM Patients from ESC Heart Failure 2025

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Dr. Alexander:
So let's review some interesting results published recently at the annual meeting of the Heart Failure Association, or HFA, of ESC, and this conference was held in Belgrade, Serbia. This is ReachMD, and I'm Kevin Alexander.

The first study that I'd like to talk about regards atrial fibrillation and ATTR-CM. We know that atrial fibrillation is quite common in ATTR cardiac amyloidosis, with 61 to 76% of patients having concomitant atrial fibrillation, and this confers significant morbidity.

Acoramidis is a highly selective, near-complete TTR stabilizer that demonstrated clinical efficacy in the phase 3 ATTRibute-CM study. And this ultimately led to the approval for acoramidis to treat ATTR-CM in Europe, the US, and Japan for both wild-type and variant ATTR-CM.

The study presented at HFA looked at the effect of acoramidis on atrial fibrillation outcomes in the ATTRibute-CM study, there's an analysis looking at the rate of cardiovascular hospitalization due to atrial fibrillation in the ATTRibute-CM population, as well as looking at the occurrence of atrial fibrillation treatment-emergent adverse events in the ATTRibute-CM study.

The takeaway is that we saw for hospitalizations that there were about 3.7% of acoramidis-treated patients who experienced at least 1 hospitalization due to atrial fibrillation or flutter, and that was compared to 5.4% of patients in the placebo group. So this is a 43% relative risk reduction of atrial fibrillation-related hospitalization in the acoramidis-treated group.

When we look at reported adverse events related to atrial fibrillation, there's about a 17% reduction in the acoramidis-treated group compared to placebo.

Other data that were presented at HFA examined outcomes in the variant or hereditary ATTR patients. Hereditary ATTR patients tend to have more aggressive disease and poorer prognosis compared to wild-type, and so it's important to understand the potential impact of TTR disease-modifying therapies in this higher-risk group.

One study that was presented looked at the effect of acoramidis on serum TTR levels in the ATTRibute-CM study. We know that an increase in serum TTR levels after initiation of a stabilizer is associated with a reduction in cardiovascular hospitalization. So the higher the rise, the greater the magnitude of reduction in hard cardiovascular outcomes.

Data shown at HFA showed that while hereditary or variant ATTR patients start at a lower baseline serum TTR, they have a marked rise in their serum TTR levels after acoramidis treatment, and this absolute level approaches what we see from wild-type patients who started at a higher baseline.

Furthermore, there are data presented at HFA looking at the clinical outcomes of variant ATTR patients treated with acoramidis. And what we found were statistically significant reductions in all-cause mortality with a hazard ratio of 0.45, time to first cardiovascular hospitalization with a hazard ratio of 0.35, and a statistically significant difference in NT-proBNP with a hazard ratio 0.35.

So taken together, all these data that were presented at HFA demonstrate the clinical efficacy of acoramidis in a few scenarios. First, there's a significant reduction in cardiovascular hospitalizations and treatment adverse events related to atrial fibrillation. And among the variant ATTR population, we see a marked rise in serum TTR after acoramidis treatment. And we also see a significant improvement in hard cardiovascular outcomes, looking at all-cause mortality, time to first cardiovascular hospitalization, and NT-proBNP.

I think these data are some of the first to show the potential impact of disease-modifying ATTR therapies on arrhythmia. And atrial fibrillation is a common comorbid condition with ATTR that many patients experience and can lead to symptoms and procedures such as ablation. So it's nice to see that starting a TTR therapy can reduce that additional burden on patients, and it's also more information for us to counsel patients on the potential benefits of treatment with a TTR stabilizer.

And in terms of variant ATTR patients, we know that they tend to have more aggressive disease and worse prognosis. And so it's important to understand from a trial data standpoint whether the effects that we see in the overall population also translate to this higher-risk group. And the data shown at HFA suggest that these higher-risk variant ATTR patients also derive significant risk reduction for hard outcomes such as mortality and time to first cardiovascular hospitalization.

That's all the time that we have today, so I'd like to thank the audience for listening in and keeping up with the evidence suggesting the clinically protective role for acoramidis in ATTR cardiomyopathy.

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