In the DEFINE-HF trial, we try to understand better what happens with the use of SGLT2 inhibitors when given to patients with heart failure and reduced ejection fraction. And specifically, the effect of dapagliflozin, one of the SGLT2 inhibitors, on patient health status, symptoms, physical limitations, quality of life, and also, natriuretic peptides, which are the biomarkers we use on heart failure commonly.
Up until we did DEFINE-HF, what we knew is that SGLT2 inhibitors are effective in preventing heart failure in high risk patients with type 2 diabetes. What we did not know is whether they will also be effective in treating heart failure in patients that already have established heart failure and also, whether those effects of SGLT2 inhibitors in established heart failure will extend to patients with and without type 2 diabetes. In a DEFINE heart failure trial, we also specifically looked at the effects of SGLT2 inhibitors early on, just after a few weeks of treatment on those parameters, the health status and the natriuretic peptides.
So what we found in the DEFINE heart failure trial is that the use of dapagliflozin increased as a proportion of patients that had a clinical meaningful improvement in either health status, which are symptoms, physical function, the quality of life, or a proportion of patients with a meaningful decline in N-terminal proBNP. That improvement was consistent regardless of presence or absence of type 2 diabetes, which is a very important finding, of course. Because we really did not know until now what would happen with this agent since they're used in patients that have heart failure, but don't have type 2 diabetes.
We did not find a significant effect of dapagliflozin in the mean N-terminal proBNP, which was one of our two dual primary endpoints. And we suspect that the reason for that was probably a very high degree of variability, or variation, in N-terminal proBNP levels, which impacted our ability to detect a statistically significant difference in immune levels of that biomarker.
How do these findings complement the DAPA-HF results?
What we found in a DAPA heart failure trial is that dapagliflozin significantly reduced the risk of cardiovascular death or hospitalization for heart failure, and also improved patient's health status as measured by Kansas City Cardiomyopathy Questionnaire at eight months. So significantly a greater proportion of patients had improvement in their symptom burden. And significantly fewer patients treated with dapagliflozin had deterioration in their symptom burden. But that was at the eight month mark.
What we actually now see in the DEFINE heart failure trial is benefits of dapagliflozin on improving the symptom burden and health status of patients with heart failure already evident at 12 weeks. And the effect size is actually quite meaningful, clinically meaningful, and also, statistically significant. And the number needed to treat to see a benefit in health status that we found in the DEFINE heart failure trial is only between seven and 10. So you only need to treat seven to 10 patients to have one patient benefit in terms of symptom improvement at just 12 weeks of treatment.
What we're seeing is really wonderful news for patients that have heart failure, regardless of whether they have type 2 diabetes or not. Because again, we have a new class of agents that appear to be highly efficacious in improving important outcomes in heart failure, reducing death, hospitalization rates, making patients feel better. And those medications, the SGLT2 inhibitors, is the entirely novel mechanism of action. Something we have never used in heart failure before. And we know from the trials that we are presenting here-- and we're just recently presented-- that the event rates continue to be very high.
So it's a population of patients that really suffers from debilitating symptoms and has high risk of bad outcomes. So having new treatments available to those patients is real exciting.
Do you think a longer duration of dapagliflozin treatment may reduce NT-proBNP levels?
When it comes to duration of treatment and how it may impact effect on biomarkers I think that answer is emerging. The trends that we kind of observed in the DEFINE heart failure trial is that as you follow the patient's longer, so at 12 weeks for example, we see more of a separation in the biomarker levels in favor of dapagliflozin. But of course, the trial was only three months in duration. In a DAPA heart failure trial, we of course, followed patients for a longer period of time. And in fact, we'll be presenting the biomarker data from that DAPA-HF over a longer period of time later today at this conference.
So I think the audience will see what those results look like.
What are the next steps for research?
I think the message that we are clearly observing here is that SGLT2 inhibitors offer a really new and exciting approach to the treatment of heart failure. And both the DEFINE heart failure and DAPA heart failure trials are just the beginning. It's not the end of the story. So we have a lot more other trials going on in space, both mechanistic studies and large outcome trials.
I think one of the important things to mention is that there will be a lot more analysis coming from both the DEFINE and DAPA HF trials in the next few months. And probably, the most critical question, in addition to understanding more about heart failure with reduced ejection fraction, is actually trying to understand what happens in patients with heart failure and preserved ejection fraction. That's a growing patient population that has high symptom burden, bad outcomes. And we have very few treatments to offer them. So I think I would say that's probably one of the most exciting things that are going on in the field. But it'll take a little bit of time before we see those results.