Researcher comment: The DAPA-HF trial

Researcher comment: The DAPA-HF trial


We studied 4,744 patients
from 20 different countries worldwide who had heart
failure with a reduced ejection fraction. But very importantly,
55% of those patients did not have type 2 diabetes. They were all very well-treated
with standard heart failure therapies. And we randomized those
patients to receive either dapagliflozin,
10 milligrams once daily, or matching placebo. We followed them for a
median of 18.2 months, and we had a primary
endpoint, which was a composite of a
worsening heart failure event or cardiovascular death. That was reduced by 26%,
a highly statistically significant benefit. Each of the components were
reduced significantly so worsening heart failure by 30%,
cardiovascular death by 18%. And maybe most
importantly of all, the benefit of dapagliflozin
was consistent in patients with and without diabetes. So what we really find
was that dapagliflozin, an SGLT2 inhibitor, appears to
be a new effective treatment for patients with heart failure
reducing hospital admission, reducing death, and
also improving symptoms. These drugs obviously
protect the kidneys, and kidneys are what
cause sodium and water retention [and]
cause the symptoms and signs of heart failure. They may also have
beneficial effects on the metabolism of the heart. That’s abnormal when
the heart fails. And they have postulated
additional benefits potentially in heart failure. For example, they may influence
some of the ion channels in the cardiomyocytes. And they have many other
different benefits that have been speculated about. The SGLT2 inhibitors as a class
have shown pretty consistent benefits in terms of preventing
the development of heart failure and improving
renal function. And I would expect
the same will be true when we look at
more of these agents for treating patients with
established heart failure. There are probably
several next steps. So one of them is
that we need to look into the DAPA-HF
database further and in particular that large
subset of patients with type 2 diabetes. We need to see whether
SGLT2 inhibitors are beneficial in the other major
type of heart failure, heart failure with preserved
ejection fraction. And there are two large trials
currently underway looking at that type of heart failure. And then this whole
amazing finding of a benefit in patients
with type 2 diabetes, we need to see whether
that might also be the case in other conditions. And two of the ongoing
chronic kidney disease trials, DAPA CKD and
EMPA-KIDNEY, are also enrolling patients who
don’t have type 2 diabetes.

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