Entresto Clinical Trials

What are Entresto Clinical Trials?

Entresto is the brand name for a combination medication given to replace ACE inhibitors in people with heart failure with decreased ejection fractions. It is made of the compounds sacubitril and valsartan. It was developed by the pharmaceutical company Novartis and was FDA-approved in 2015. With over two million prescriptions filled each year, Entersto is the 219th most prescribed medicine in the US.

Why Is Entresto Being Studied In Clinical Trials?

The need to understand the effectiveness of Entresto for different cases of heart failure is one of the driving forces behind its clinical trials. So far, it has been shown not to work effectively on its own for patients with heart failure and LVEF (HFpEF). However, if taken with other medications, it is more effective. This opens the door to discovering other combinations to help improve prognosis.

There is also a lack of information about Entresto's interaction with different ethnicities, especially considering that one of its most severe side effects, angioedema is a common side effect in black patients.

How Does Entresto Treatment Work?

Entresto is made of two medications: sacubitril and valsartan. Sacubitril inhibits the protein neprilysin. This increases the level of vasoactive peptides in the blood, dilating blood vessels and decreasing extracellular fluid. Therefore sacubitril can improve blood flow and reduce fluid retention.

Valsartan is an angiotensin receptor blocker. It blocks the hormone angiotensin (known to constrict blood vessels), thus keeping them dilated to reduce blood pressure. This action makes it easier for the heart to pump blood.

Entresto has adverse side effects such as hypotension, hyperkalemia, dry cough, dizziness, and reduced kidney function. A rare but severe reaction is angioedema. This condition causes the face and lips to swell up but is seen in less than 1% of patients. Entresto is not given to pregnant women because valsartan causes birth defects and fetal death.

What Are Some of the Breakthrough Clinical Trials Involving Entresto?

2019: Known as the PARAGON-HF trial, this study was funded by Novartis partly because of the controversy surrounding the initial PARADIGM-HF trial used for FDA approval. The PARADIGM trial was criticized for having an inadequate risk-benefit ratio and participants with inconsistent cases of heart failure. This time participants with heart failure and reduced left ventricular ejection fraction (i.e., LVEF greater than 45%) were studied under the effect of Entresto without any other medication. Entresto was proven to be more effective than enalapril, another commonly prescribed ACE inhibitor.

2018: This review was conducted by Cochrane, a British-based organization that conducts independent research on healthcare data. This report analyzed data from over 35 clinical trials that studied treatments for patients with heart failure and LVEF (also known as HFpEF). The results showed that although current drug therapies are still the best options for heart failure-related symptoms such as hypertension, the addition of Entresto is beneficial. It decreased the risk of death mortality due to cardiovascular problems without any increase in side effects.