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Entresto, a combination of Sacubitril and Valsartan, can be initiated early in hospitalized patients after an acute heart failure episode

Data from the TRANSITION study presented at the European Society of Cardiology ( ESC ) Congress in Munich ( Germany ) has shown that Entresto ( Sacubitril / Valsartan ) can be initiated early and safely in a wide range of heart failure ( HF ) patients with reduced ejection fraction ( HFrEF ) who have been stabilized after hospitalization due to an acute heart failure episode.
Patients involved in the study included those with no prior experience of Entresto or conventional therapies for heart failure, as well as those with prior experience of conventional therapies for heart failure.

About half of all heart failure patients have reduced ejection fraction, and optimizing treatment for these patients according to guidelines is critical to reduce the likelihood of another acute episode or dying.
However, there is often hesitancy to initiate a new treatment after a hospitalization as these patients are considered vulnerable and unable to tolerate changes in their medication.

In the weeks following an episode of acute heart failure, patients are very vulnerable and face a high risk of re-hospitalization and death.
The PARADIGM-HF study showed that the combination of Sacubitril and Valsartan reduces heart failure-related hospitalizations, re-hospitalization and death.
TRANSITION has shown that Sacubitril and Valsartan can be initiated early and safely in patients shortly after an acute heart failure episode, providing physicians with added confidence to optimize their care with innovative medicines in heart failure treatment.

In TRANSITION, the safety and tolerability of Entresto were assessed in HFrEF patients after they have been stabilized following an acute heart failure episode.
Patients were randomized to initiate Entresto 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 Entresto for 2 weeks or longer without interruption and about half of patients in the study achieved the primary endpoint which was a target dose of 200 mg of Entresto twice daily within 10 weeks in both groups.
The number of patients who met the primary and secondary endpoints was similar across both treatment arms.
The incidence of adverse events and discontinuations of Entresto due to adverse events was also similar in both the in-hospital and the out-patient setting.

TRANSITION is a randomized, phase IV, multicenter, open-label, parallel-group study, which assessed the safety and tolerability of Entresto in 1,002 HFrEF patients, from 156 hospitals worldwide, after stabilization following hospitalization for acute heart failure, when treatment was started in hospital or shortly after leaving hospital.
Patients were grouped based on their pre-admission treatment status: those who were receiving an angiotensin converting enzyme inhibitor ( ACEI ) or an angiotensin receptor blocker ( ARB ), or those with no prior experience with an ACEI/ARB.
Following screening and randomization to Entresto, the study comprised a 10 week treatment period followed by a 16 week follow-up phase.
The primary and secondary endpoints were the number of patients achieving the target dose of Entresto of 200 mg twice daily ( bid ) at week 10 ( regardless of previous dose interruption or down-titration ), and number of patients maintaining 100 mg or 200 mg bid for at least two weeks leading to week 10 after randomization, respectively.
The study protocol took into account the needs of the practicing cardiologists, and enabled investigators to select the appropriate starting dose of Entresto and dose adjustments due to clinical circumstances, allowing for differences between international hospitals and healthcare settings.

Entresto is a twice-a-day medicine that reduces the strain on the failing heart. It does this by enhancing the protective neurohormonal systems ( natriuretic peptide system ) while simultaneously inhibiting the harmful effects of the overactive renin-angiotensin-aldosterone system ( RAAS ).
Other common heart failure medicines, called angiotensin converting enzyme ( ACE ) inhibitors and angiotensin II receptor blockers ( ARBs ), only block the harmful effects of the overactive RAAS.
Entresto contains the neprilysin inhibitor Sacubitril and the angiotensin receptor blocker ( ARB ) Valsartan.

In European Union, Entresto is indicated in adult patients for the treatment of symptomatic chronic heart failure with reduced ejection fraction.
In the United States, Entresto is indicated for the treatment of heart failure ( NYHA class II-IV ) in patients with systolic dysfunction.
It has been shown to reduce the rate of cardiovascular death, heart failure hospitalization and 30-day hospital readmission compared to Enalapril, to reduce the rate of all-cause mortality compared to Enalapril, and to improve aspects of health-related quality of life ( including physical and social activities ) compared to Enalapril.
Entresto is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other angiotensin receptor blocker.

Heart failure is a serious progressive disease with debilitating symptoms. Patients with heart failure are at risk of a sudden worsening of the disease that requires urgent care in hospital and it is the number one reason for hospitalization in people over 65 years.
Of the 26 million people worldwide living with heart failure, 83% of patients with heart failure are hospitalized due to an acute HF episode at least once, and nearly half ( 43% ) are hospitalized at least four times.
Every year, there are approximately one million hospitalizations due to heart failure in the US and Europe, and on average, a HF patient remains in hospital for five to 10 days.
Due to this, heart failure presents a major and growing health-economic burden that currently costs the world economy $108 billion every year, which accounts for both direct and indirect costs. ( Xagena )

Source: Novartis, 2018