TRANSLATE-HF study establishes the potential
for broad use of the only SGLT2 inhibitor indicated in patients
with heart failure with reduced ejection fraction with and without
diabetes
New data from a large, contemporary US hospitalized heart
failure (HF) registry confirms that four out of five (81.1%)
patients with NYHA class II-IV HF with reduced ejection fraction
(HFrEF), with and without type 2 diabetes (T2D), could be
considered as eligible candidates for sodium glucose co-transporter
2 (SGLT2) inhibitor FARXIGA® (dapagliflozin). The analysis,
presented today at the American Heart Association’s (AHA)
Scientific Sessions 2020, evaluated records of more than 150,000
patients who were hospitalized for HFrEF at over 400 US hospital
centers, leveraging data from the AHA’s Get With The
Guidelines-Heart Failure (GWTG-HF) registry.
FARXIGA is the only SGLT2 inhibitor approved by the US Food and
Drug Administration (FDA) to reduce the risk of cardiovascular (CV)
death and hospitalization for HF (hHF) in adults with HFrEF with
and without T2D. This indication is based on the positive results
from the landmark Phase III DAPA-HF trial, which showed FARXIGA, in
addition to standard of care, reduced the risk of the composite
outcome of CV death or the risk of hHF versus placebo by 26%
(absolute risk reduction [ARR] = 5% [event rate/100 patient years:
11.6 vs 15.6, respectively]; p<0.0001) in patients with HFrEF.
The clinical characteristics of treatment candidates in the
TRANSLATE-HF analysis were comparable to those in the DAPA-HF
trial.
Muthiah Vaduganathan, MD, MPH, first author of the study, a
cardiologist at Brigham and Women’s Hospital and faculty at Harvard
Medical School, said: “There is a tremendous unmet need for people
living with heart failure with reduced ejection fraction. While
we’ve seen recent treatment innovation in this space, there remains
a gap in its translation to clinical practice. These study results
support the use of this treatment in a broad population of these
patients and reinforce the urgent need for clinical uptake.”
Leandro Boer, MD, Vice President, US Medical Affairs, CVMD,
said: “AstraZeneca is proud to work with the AHA to apply the
established scientific evidence of FARXIGA in a real-world clinical
setting for patients with heart failure with reduced ejection
fraction. As an organization, we believe clinical practice must
swiftly follow the science to ensure the most innovative treatment
advancements are considered for patients. Through this analysis,
we’re hopeful that more patients in need may benefit from treatment
with FARXIGA.”
This analysis is the first in a series of studies under the
TRANSLATE-HF research platform, developed by the AHA with support
and partnership from AstraZeneca. The series focuses on
evidence-based treatment for patients with HF and will utilize data
from the GWTG-HF registry to address critical knowledge gaps and
potential barriers to prescribing the latest, evidence-based
therapies for patients diagnosed with HF. Findings will also help
to identify potential areas for increasing implementation efforts
that can improve quality of care delivery, and ultimately, patient
outcomes. This first analysis was simultaneously published today in
JAMA Cardiology.
In the US, FARXIGA is indicated as an adjunct to diet and
exercise to improve glycemic control in adults with T2D and to
reduce the risk of hHF in patients with T2D and established CV
disease or multiple CV risk factors. In May, FARXIGA was approved
in the US to reduce the risk of CV death and hHF in adults with
HFrEF, with and without T2D.
INDICATIONS AND LIMITATIONS OF USE for FARXIGA®
(dapagliflozin)
FARXIGA is indicated:
- as an adjunct to diet and exercise to improve glycemic control
in adults with type 2 diabetes mellitus
- to reduce the risk of hospitalization for heart failure in
adults with type 2 diabetes mellitus and established cardiovascular
(CV) disease or multiple CV risk factors
- to reduce the risk of cardiovascular death and hospitalization
for heart failure in adults with heart failure (NYHA class II-IV)
with reduced ejection fraction
FARXIGA is not recommended for patients with type 1 diabetes
mellitus or for the treatment of diabetic ketoacidosis.
IMPORTANT SAFETY INFORMATION for FARXIGA® (dapagliflozin) 5
mg and 10 mg tablets
Contraindications
- Prior serious hypersensitivity reaction to FARXIGA
- Patients with severe renal impairment (eGFR <30 mL/min/1.73
m2) being treated for glycemic control without established CV
disease or multiple CV risk factors
- Patients on dialysis
Warnings and Precautions
- Volume Depletion: FARXIGA can cause intravascular volume
depletion which may manifest as symptomatic hypotension or acute
transient changes in creatinine. Acute kidney injury requiring
hospitalization and dialysis has been reported in patients with
type 2 diabetes receiving SGLT2 inhibitors, including FARXIGA.
Patients with impaired renal function (eGFR less than 60
mL/min/1.73 m2), elderly patients, or patients on loop diuretics
may be at increased risk for volume depletion or hypotension.
Before initiating FARXIGA in these patients, assess volume status
and renal function. After initiating therapy, monitor for signs and
symptoms of hypotension and renal function
- Ketoacidosis in Diabetes Mellitus has been reported in
patients with type 1 and type 2 diabetes receiving FARXIGA. Some
cases were fatal. Assess patients who present with signs and
symptoms of metabolic acidosis for ketoacidosis, regardless of
blood glucose level. If suspected, discontinue FARXIGA, evaluate
and treat promptly. Before initiating FARXIGA, consider risk
factors for ketoacidosis. Patients on FARXIGA may require
monitoring and temporary discontinuation in situations known to
predispose to ketoacidosis
- Urosepsis and Pyelonephritis: SGLT2 inhibitors increase
the risk for urinary tract infections (UTIs) and serious UTIs have
been reported with FARXIGA. Evaluate for signs and symptoms of UTIs
and treat promptly
- Hypoglycemia: FARXIGA can increase the risk of
hypoglycemia when coadministered with insulin and insulin
secretagogues. Consider lowering the dose of these agents when
coadministered with FARXIGA
- Necrotizing Fasciitis of the Perineum (Fournier’s
Gangrene): Rare but serious, life-threatening cases have been
reported in patients with diabetes mellitus receiving SGLT2
inhibitors including FARXIGA. Cases have been reported in females
and males. Serious outcomes have included hospitalization,
surgeries, and death. Assess patients presenting with pain or
tenderness, erythema, swelling in the genital or perineal area,
along with fever or malaise. If suspected, institute prompt
treatment and discontinue FARXIGA
- Genital Mycotic Infections: FARXIGA increases the risk
of genital mycotic infections, particularly in patients with prior
genital mycotic infections. Monitor and treat appropriately
Adverse Reactions
In a pool of 12 placebo-controlled studies, the most common
adverse reactions (≥5%) associated with FARXIGA 5 mg, 10 mg, and
placebo respectively were female genital mycotic infections (8.4%
vs 6.9% vs 1.5%), nasopharyngitis (6.6% vs 6.3% vs 6.2%), and
urinary tract infections (5.7% vs 4.3% vs 3.7%).
Use in Specific Populations
- Pregnancy: Advise females of potential risk to a fetus
especially during the second and third trimesters
- Lactation: FARXIGA is not recommended when
breastfeeding
DOSING
- To improve glycemic control in patients with T2D, the
recommended starting dose of FARXIGA is 5 mg orally once daily,
taken in the morning. In patients tolerating FARXIGA 5 mg once
daily who require additional glycemic control, the dose can be
increased to 10 mg once daily
- To reduce the risk of hospitalization for heart failure in
patients with T2D and established CV disease or multiple CV risk
factors, the recommended dose of FARXIGA is 10 mg orally once
daily
- To reduce the risk of CV death and hospitalization for heart
failure in patients with HFrEF, the recommended dose of FARXIGA is
10 mg orally once daily
Please see accompanying US Full Prescribing Information and
Medication Guide for FARXIGA.
TRANSLATE-HF
TRANSLATE-HF is a contemporary US hospitalized heart failure
(HF) registry study designed to evaluate the eligibility of
patients hospitalized with HF with reduced ejection fraction
(HFrEF), with or without type 2 diabetes, for treatment with the
SGLT2 inhibitor dapagliflozin based on the US Food and Drug
Administration (FDA) label (excluding eGFR<30 mL/min/1.73 m2,
dialysis, or type 1 DM). The study analyzed records of 154,714
patients with HFrEF hospitalized at 406 hospital centers across the
US participating in the American Heart Association’s (AHA) Get With
The Guidelines®-Heart Failure (GWTG-HF) quality improvement
initiative admitted between January 2014 – September 2019. The
TRANSLATE-HF research platform, commissioned by the AHA with
support and partnership from AstraZeneca, includes a series studies
that focus on evidence-based treatment for patients with HF.
DapaCare Clinical Program
AstraZeneca is taking a holistic, patient-centric approach to
disease management by addressing the underlying morbidity,
mortality and organ damage associated with CV, metabolic and renal
diseases. Due to the interconnectivity of these diseases,
AstraZeneca has developed the DapaCare clinical program to explore
the CV and renal profile of FARXIGA in people with and without T2D.
The clinical program will enroll nearly 30,000 patients in
randomized clinical trials and is supported by a multinational
real-world evidence study. DapaCare will generate data across a
spectrum of people with established CV disease, CV risk factors and
varying stages of renal disease, both with and without T2D,
providing healthcare providers with evidence needed to improve
patient outcomes.
FARXIGA has also been explored for the treatment of chronic
kidney disease (CKD) in the DAPA-CKD trial. DapaCare underscores
our commitment to following the science by pursuing a holistic
patient approach to address the multiple risk factors associated
with CV, renal and metabolic diseases.
Heart Failure
HF is a life-threatening disease in which the heart cannot pump
enough blood around the body. It affects approximately 64 million
people worldwide (at least half of which have a reduced ejection
fraction) and six million in the US. It is a chronic disease where
half of patients will die within five years of diagnosis. There are
two main categories of HF related to ejection fraction (EF), a
measurement of the percentage of blood leaving the heart each time
it contracts: HFrEF and heart failure with preserved ejection
fraction (HFpEF). HFrEF occurs when the left ventricle (LV) muscle
is not able to contract adequately and therefore, expels less
oxygen-rich blood into the body. HF remains as fatal as some of the
most common cancers in both men (prostate and bladder cancers) and
women (breast cancer). It is the leading cause of hospitalization
for those over the age of 65 and represents a significant clinical
and economic burden.
DAPA-HF
DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in
Heart Failure) is an international, multi-center, parallel-group,
randomized, double-blinded trial in 4,744 patients with heart
failure and reduced ejection fraction (LVEF ≤ 40%), with and
without T2D, designed to evaluate the effect of FARXIGA 10mg,
compared with placebo, given once daily in addition to standard of
care. The primary composite endpoint was time to the first
occurrence of a worsening heart failure event (hospitalization or
equivalent event; i.e. an urgent heart failure visit), or
cardiovascular death. The median duration of follow-up was 18.2
months.
AstraZeneca in CV, Renal & Metabolism (CVMD)
CV, renal and metabolism together form one of AstraZeneca’s main
therapy areas and a key growth driver for the Company. By following
the science to understand more clearly the underlying links between
the heart, kidneys and pancreas, AstraZeneca is investing in a
portfolio of medicines to protect organs and improve outcomes by
slowing disease progression, reducing risks and tackling
co-morbidities. Our ambition is to modify or halt the natural
course of CVMD diseases and potentially regenerate organs and
restore function, by continuing to deliver transformative science
that improves treatment practices and CV health for millions of
patients worldwide.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialization of
prescription medicines, primarily for the treatment of diseases in
three therapy areas - Oncology, Cardiovascular, Renal &
Metabolism and Respiratory & Immunology. AstraZeneca operates
in over 100 countries and its innovative medicines are used by
millions of patients worldwide. For more information, please visit
www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.
US-47533 Last Updated 11/20
View source
version on businesswire.com: https://www.businesswire.com/news/home/20201113005476/en/
Media Inquiries US Media Line Michele Meixell / Brendan
McEvoy +1 302 885 2677
AstraZeneca (NYSE:AZN)
Historical Stock Chart
From Aug 2024 to Sep 2024
AstraZeneca (NYSE:AZN)
Historical Stock Chart
From Sep 2023 to Sep 2024