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DAPA HF study results

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(calm music) – Hello, I’m John McMurray
from the University of Glasgow in the United Kingdom. And I’m the Principal Investigator of the Dapagliflozin in Heart
Failure With Reduced Ejection Fraction trial, DAPA- HF. And I’ll give you a short
summary of the design and principle findings
of the DAPA-HF trial. So, we’ve known for some time that sodium glucose
co-transporter two inhibitors, SGLT-2 inhibitors, can
prevent the development of heart failure in patients
with Type II Diabetes. What we didn’t know is whether
or not SGLT-2 inhibitors might be a treatment for patients with established heart failure. There’s also some experimental evidence that these drugs may have benefits that are independent of glucose lowering, and therefor another interesting question was whether or not they
might be useful treatment for patients with heart failure
who do not have diabetes. Therefor we conducted the DAPA-HF trial in which we randomized
patients with heart failure and reduced ejection fraction to either Dapagliflozin,
10 milligrams, once daily, or placebo. And importantly, we randomized
patients with HFrEF, both with and without diabetes. The design of our trial
was very straightforward. We enrolled typical HFrEF patients. They had to have an
ejection fraction below 40%. And they had to have a modest elevation in
natriuretic peptides. We had very few exclusion criteria. The two principle exclusion criteria were an estimated glomerular
filtration rate of less than 30 and a systolic blood pressure of less than 95 millimeters of mercury. We enrolled 4,744 patients. We followed them for a
median of 18.2 months. They were very well treated with contemporary pharmacological therapy, including a beta blocker
in 96% of patients, a renin-angiotensin system
blocker in 94% of patients, and antimineralocorticoid
receptor antagonist, and aldosterone receptor
antagonist in 71% of patients. Our primary endpoint was the composite of a worsening heart failure event, or cardiovascular mortality. We saw a 26% relative risk reduction in the primary composite endpoint. That was a highly statistically
significant benefit. The number needed to
treat to prevent one event over the 18 months of
median follow-up, was 21. Both of the components
of that composite outcome were also individually
reduced significantly. So there was 30% reduction in a worsening heart failure event. Most of those events were, in fact, heart failure hospitalizations. Heart failure hospitalization
was reduced by 30%. And there was a significant 18% reduction in cardiovascular mortality. We’d a number of secondary endpoints, but I’ll just mention two of those. The first is patient-reported symptoms measured using the Kansas City
Cardiomyopathy Questionnaire. There was an overall
improvement with Dapagliflozin that was statistically significant. More patients in the Dapagliflozin group had a clinically meaningful
improvement in symptoms. Fewer patients in the Dapagliflozin group had a clinically important
deterioration in symptoms. The other secondary
outcome I will mention, because of its importance, is all-cause mortality. And we saw a statistically
significant 17% reduction in all-cause mortality. We were, of course, concerned
about safety and tolerability. We did not find that any
adverse event was more common in the Dapagliflozin group
than in the placebo group. Dapagliflozin was very well tolerated. Only 10.7% of patients
discontinued study drug over the course of the study. That was the same
proportion, approximately, as in the placebo group. Maybe one last and critically
important point to make is that the benefit that we
saw for the primary outcome was identical in patients with diabetes and in HFrEF patients without diabetes. In other words, this drug was effective even in heart failure patients
who were not diabetic. So, in summary and conclusion, we felt that we’d observed significant, clinically important reductions in worsening heart failure events and in cardiovascular mortality. And in addition, we saw an
improvement in patient symptoms. These benefits were seen in all the major subgroups we examined, and in particular, patients
who were not diabetic. Dapagliflozin was well tolerated and was infrequently discontinued. So, in summary, we believe
that we’ve identified a completely new approach to the treatment of heart failure with
reduced ejection fraction. This is a drug that doesn’t act in the way that most of our existing heart
failure therapies act, i.e. through neurohumoral modulation. This treatment, of course, is available for diabetic patients, today, and the guidelines recommend its use in diabetic patients. So, of course, patients with
heart failure and diabetes could be treated anytime
with this particular agent. The non-diabetic subgroup
of patients, of course, we can’t advocate using Dapagliflozin in those individuals yet. The drug is not labeled
for use in non-diabetics. That has to undergo regulation review. And of course we have to wait for the guideline recommendations. (calm music)

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