Novartis has announced new results from a real-world database study of patients in Germany prescribed Entresto® (sacubitril/valsartan) for heart failure with reduced ejection fraction (HFrEF). The findings further substantiate the beneficial effect of Entresto on heart failure symptoms and patients' quality of life observed in the PARADIGM-HF study and in other real-world cohorts. Results were presented as a poster at the American Heart Association's Scientific Sessions 2017.

"People living with heart failure experience symptoms that severely limit their physical activities and quality of life," said Shreeram Aradhye, Chief Medical Officer and Global Head, Medical Affairs, Novartis Pharmaceuticals. "We are excited to see the growing body of evidence showing that Entresto has a beneficial effect on the quality of life in heart failure, in addition to reducing cardiovascular death and heart failure hospitalization."

The non-interventional, retrospective database study examined changes in clinical characteristics of 1,643 patients in Germany on Entresto in the 12 months after their first dose. All patients with available data were analyzed and the results included:

The majority of patients had a stable New York Heart Association (NYHA) class over time. Before Entresto more patients had a trend of worsening NYHA class. The trend of worsening NYHA was reversed after switching to Entresto at Day 90 (n=121) and 180 (n=81)[1]. NYHA classification is used to grade the severity of a patient's heart failure symptoms, with physicians determining class based on specific criteria (e.g., the level of discomfort associated with physical activity)

There was an approximately 30% mean decrease (-503pg/mg; p<0.001; n=119) in NT-proBNP, a blood marker used to diagnose heart failure and to determine prognosis[1]. Levels of NT-proBNP are typically higher in patients with worse outcomes[3]

The majority of patients had a documented first dose of Entresto at the lowest level (24/26mg twice daily). Of these patients, 36% from the primary care practices and 41% from the cardiology practices had their dose up-titrated during follow-up; however, <11% received the target dose (97/103mg twice daily) at the last recorded prescription

These results are consistent with other real world data published in 2017, which show that Entresto has a beneficial impact on quality of life:

Canada (n=276): 45% of patients switched to Entresto report feeling better after four weeks, 56% after 12 weeks[4]

France (n=200): in patients treated with Entresto improvement in NYHA class and exercise capacity was observed[2]

These data results were also consistent with post-hoc analyses of the landmark PARADIGM-HF clinical trial published between 2015 and 2017, which show that:

In surviving patients, treatment with Entresto improved patients' quality of life, including heart failure symptoms and physical limitations as compared with enalapril, as measured by KCCQ[5]; this effect is sustained over 36 months

Entresto improved seven out of 10 activities when compared with enalapril, with the most significant changes in household chores and intimate/sexual relationships[6]

Among patients who had been hospitalized for heart failure, Entresto has been shown to slow the further decline in health-related quality of life in approximately half of patients compared to enalapril, as measured by KCCQ[7]

Patients were less likely to have NYHA functional class deterioration on Entresto compared with enalapril[8]

KCCQ is a self-administered health-related quality of life (HRQL) measure for HF patients, with higher scores indicating fewer symptoms and physical limitations associated with HF[5]. The questionnaire quantifies physical function, symptoms (recent change, frequency and burden), social function, self-efficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.