How this popular drug could help treat heart failure

In two new studies, researchers found how the heart drug sacubitril/valsartan could improve the structure and function of the failing heart.

Treatment with sacubitril/valsartan, a combination angiotensin receptor-neprilysin inhibitor (ARNI), could lower rates of death and hospitalization in certain types of heart failure patients.

However, the mechanisms by which the drug actually affects the heart are poorly understood.

These two new studies suggest a key effect of ARNI is to reverse cardiac remodeling—a finding that could lead to better management of this condition.

In heart failure, progressive cardiac remodeling leads to changes in the shape and size of the heart, contributing to weakened heart function and progressive symptoms such as shortness of breath, reduced exercise capacity, and fluid retention.

The researchers found that treatment with ARNI was linked to big improvements in cardiac structure and function and that these changes were strongly linked to reductions in blood levels of the biomarker amino-terminal-pro-B-type natriuretic peptide (NT-proBNP).

Levels of NT-proBNP levels are tightly linked to the risk of death and heart failure hospitalization.

In one study, the researchers examined nearly 800 patients with heart failure and reduced ejection fraction who were over the age of 65 and had just started on ARNI.

Patients were followed for one year and monitored serially with blood tests to measure cardiac biomarkers and echocardiography to assess cardiac structure and function.

Treatment with ARNI rapidly and strongly lowered levels of NT-proBNP at one year, and this reduction in levels of the biomarker was strongly linked to improvements in cardiac structure and function at both six months and one year.

In the other study, the team examined 464 patients with chronic heart failure, reduced ejection fraction, and history of high blood pressure who received treatment with ARNI and followed them for a period of 12 weeks.

At 12 weeks, no difference was noted between the two treatments with regard to change in aortic impedance—a measure of aortic stiffness.

However, big reductions were seen with ARNI in secondary measures of cardiac structure and function.

The findings suggest that the clinical benefits of ARNI are likely unrelated to changes in central aortic stiffness, but might be related to favorable early effects of neprilysin inhibition (one of the primary effects of ARNI) on myocardial remodeling.

One author of the two studies is France. Scott Solomon, MD, director of Noninvasive Cardiology.

The two studies are published in the Journal of the American Medical Association.

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