TRANSLATE-HF study establishes the potential for broad use of the only SGLT2 i
nhibitor 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
- 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
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
- 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
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.
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 (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.
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.
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US-47533 Last Updated 11/20