Novartis announces Entresto ™ ▼ can be initiated with safety and tolerability in patients with heart failure

Image of a heart Novartis announces Entresto

Novartis presented new data from the TRANSITION study at The British Society of Heart Failure (BSH) 21st Annual Autumn Meeting (29-30 November) in London. This data, presented for the first time in the UK, showed that Entresto™ ▼ (sacubitril/valsartan) was well tolerated in heart failure patients with reduced ejection fraction (HFrEF), who have been stabilised after hospitalisation due to an acute decompensation heart failure episode (ADHF). The results from TRANSITION are supportive of the safety and tolerability data from the PARADIGM-HF study, which demonstrated sacubitril/valsartan has important clinical benefits for heart failure patients.

Heart failure is a serious progressive disease with 83% of patients hospitalised at least once for an ADHF during the course of their condition. Hospitalisation provides an opportunity for physicians to optimise heart failure treatment according to guidelines to reduce the likelihood of hospital readmission and death, reduce the burden of hospitalisations, and improve patient outcomes.

In TRANSITION, the safety and tolerability of sacubitril/valsartan were assessed in HFrEF patients after they had been stabilised following an ADHF. Patients were randomised to initiate sacubitril/valsartan therapy either in the hospital (pre-discharge) or shortly after leaving the hospital (post-discharge). At 10 weeks, more than 86% of patients were receiving sacubitril/valsartan for two weeks or longer without interruption. About half of the patients also achieved the primary endpoint which was a target dose of 97 mg/103 mg of sacubitril/valsartan twice daily within 10 weeks in both groups. The license recommended starting dose of sacubitril/valsartan is one tablet of 49 mg/51 mg twice daily.

Dr Klaus Witte, Senior Lecturer and Consultant Cardiologist, University of Leeds and Leeds Teaching Hospitals NHS Trust, who presented the data said, “These results are important. They provide confidence that sacubitril/valsartan is well tolerated shortly after stabilisation following an episode of ADHF. We already know that time is of the essence in patients with heart failure: getting patients onto the right tablets as soon as possible can save lives. It is therefore critical that we act with urgency and focus, with the aim of reducing the long-term risk of hospitalisation and cardiovascular death. Whether it is before or after the discharge of stable patients, physicians now have added confidence to prescribe sacubitril/valsartan at the earliest opportunity.”

These results support data from PARADIGM-HF, the largest clinical study ever conducted in heart failure comparing sacubitril/valsartan to enalapril, the standard of care at the time. PARADIGM-HF showed that sacubitril/valsartan significantly reduced the risk of death by 20% and hospitalisation by 21% in patients with heart failure versus enalapril2. These results in numbers show that treating 1,000 patients with sacubitril/valsartan instead of enalapril over a median treatment period of 27 months avoided 32 cardiovascular deaths, 111 hospitalisations (for any reason) and 53 hospitalisations specifically for heart failure.

In addition, Novartis presented data from other trials such as PIONEER-HF, conducted in the U.S, at the 21st BSH Annual Autumn Meeting. Similar to the ARIADNE study results that were shown at the ESC Congress 2018 and TRANSITION, PIONEER-HF also demonstrated comparable safety data, with short-term exploratory endpoints suggesting a clinical benefit when sacubitril/valsartan was introduced to stable HFrEF patients pre-discharge compared with enalapril, which is often regarded as the current standard of care.

Simon Williams, Consultant Cardiologist at Wythenshawe Hospital and Chair-Elect of the BSH, said, “In PARADIGM-HF, we saw a significant reduction in deaths and re-hospitalisation of heart failure patients who were ambulatory. The fact that TRANSITION shows that sacubitril/valsartan can also be initiated when a patient is stabilised post-ADHF is highly reassuring. These two trials provide consistent evidence and should provide clinicians with further confidence to use sacubitril/valsartan in line with NICE recommendations.”