Important New Analysis Shows that Novartis' Entresto® is Associated
"Heart failure hospitalizations can significantly decrease a patient's quality of life and lead to poorer outcomes," said Eldrin F. Lewis, MD, MPH, Associate Physician at Brigham and Women's Hospital and Associate Professor of Medicine, Harvard Medical School. "Heart failure management must focus on strategies to reduce this decline by better managing symptoms which can lead to hospitalization. These analyses suggest that sacubitril-valsartan may help mitigate the impact of heart failure hospitalization on a patient's health-related quality of life, and make a strong case for it as part of optimal treatment of heart failure with reduced ejection fraction."
Regardless of treatment, patients experienced a decrease in HRQL following a HF hospitalization. The first analysis demonstrated that the decline in HRQL associated with a HF hospitalization among Entresto patients was significantly less compared to that of patients taking enalapril.
6,981 patients in PARADIGM-HF completed a Kansas City Cardiomyopathy Questionnaire (KCCQ) to measure HRQL at baseline and at eight months of treatment; during those eight months, 305 patients were hospitalized for HF.
Among patients who had been hospitalized for HF, those on Entresto experienced lower declines in HRQL (approximately half) compared to those on enalapril (5.11 point decline vs. 10.77 point decline in KCCQ Clinical Summary Score (KCCQ-CSS) for Entresto and enalapril, respectively; p=0.003).
Patients in the PARADIGM-HF study completed a KCCQ at randomization, four months, eight months and annually. KCCQ is a self-administered HRQL measure for HF patients, and the clinical summary score of the KCCQ uses a scale from 0 to 100, with higher scores indicating fewer symptoms and physical limitations associated with HF. In the overall patient population of PARADIGM-HF, at eight months of treatment, HRQL, as measured by the KCCQ clinical summary score, declined less in patients treated with Entresto than those patients treated with enalapril (2.99 point decline vs. 4.63 point decline for Entresto and enalapril, respectively; least squares mean of the between-group difference 1.64; 95% CI 0.63-2.65; p=0.001).
A second post-hoc analysis examined the association between HRQL and patient outcomes in the overall patient population, and found that clinically meaningful worsening in HRQL scores (defined as a >= 5 point decrease in the KCCQ clinical summary score) after four months of treatment was associated with an increased risk of worse clinical outcomes, including CV death or HF hospitalization.
7,155 patients completed a KCCQ at baseline and at four months of treatment.
Patients with a decline in HRQL, defined by a decrease of at least five points in the KCCQ clinical summary score at four months, were subsequently at a 24% higher risk of CV death (p=0.009) or 28% higher risk of HF hospitalization (p=0.004).
"We have already seen from PARADIGM-HF that Entresto significantly reduces the risk of cardiovascular death and heart failure hospitalization in heart failure patients with reduced ejection fraction." said Vasant Narasimhan, Global Head, Drug Development and Chief Medical Officer, Novartis. "This new analysis of the data demonstrates that Entresto can also help reduce the serious impact on quality of life associated with heart failure, and further reinforces the potential of this medicine to improve the outlook for patients living with this debilitating condition."