Sacubitril/Valsartan Combo Found in Analysis to Improve Heart Function

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by Steve Bryson, PhD |

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Sacubitril/valsartan, a fixed-dose combination oral therapy approved for heart failure, was found to improve right heart function and lower pulmonary blood pressure, according to a new pooled analysis of multiple studies.

This meta-analysis supports a new therapeutic role for sacubitril/valsartan for people with pulmonary hypertension (PH) associated with heart failure, the researchers said.

However, given the small study size, larger, controlled clinical trials are needed to confirm these findings, they added.

“S/V  [sacubitril/valsartan] had a significant therapeutic effect on [heart] function within 6 months, increasing over time,” the team wrote, adding that it’s “of extreme importance for eligible patients to initiate S/V therapy as early as possible.”

The study, “Effect of Sacubitril/Valsartan on the Right Ventricular Function and Pulmonary Hypertension in Patients With Heart Failure With Reduced Ejection Fraction: A Systematic Review and Meta‐Analysis of Observational Studies,” was published in the Journal of the American Heart Association.

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Sold under the brand name Entresto, sacubitril/valsartan is a combination medication, available in a fixed dose, that is currently approved as a first-line treatment for heart failure with reduced ejection fraction (HFrEF) — when the left side of the heart does not contract effectively to pump blood throughout the body. This combination acts as a vasodilator that opens (dilates) blood vessels.

Because of its various underlying causes, many people with HFrEF also have co-existing impairment to the right side of the heart, which pumps blood through the vessels in the lungs. These blood vessels are called pulmonary arteries. As a result of such damage, PH — characterized by increased blood pressure in pulmonary arteries — occurs in up to 75% of HFrEF patients.

The effect of sacubitril/valsartan on left heart function is well-established, but its impact on right heart function remains unclear. Some observational studies reported benefits from the medicine in right heart impairment, but no efficacy has also been reported.

To learn more, researchers at the Peking Union Medical College, in China, conducted a meta-analysis. They pooled the results of studies that evaluated the impact of sacubitril/valsartan on right heart ventricle function and PH in people with HFrEF.

Medical databases were searched for published reports that included adults with HFrEF who were treated with sacubitril/valsartan from the beginning of each study. Patients must have had right heart function and pulmonary blood pressure data, by echocardiogram, before and after treatment; they also had to have been followed for at least three months.

The team identified 10 observational studies that included a total of 875 patients, with a mean age of 62.2 years, of whom 74% were men. Six studies were from Italy, and one each came from Turkey, France, Greece, and Slovenia.

With sacubitril/valsartan treatment, the pooled data across eight studies — with 732 patients — showed a significant improvement in overall right heart function. This was measured by an increase in the tricuspid annular plane systolic excursion (TAPSE), considered one of the most clinically useful echocardiographic assessments. Two studies, involving 186 patients, reported improvement in the tricuspid annular peak systolic velocity (S’), a separate measure of right heart function.

In terms of PH, treatment with sacubitril/valsartan significantly reduced pulmonary blood pressure. That improvement was found in six studies (419 patients) that measured systolic pulmonary artery pressure (sPAP) and in two studies (350 patients) by measuring mean pulmonary arterial pressure (mPAP).

At the same time, and consistent with previous studies, the combination therapy improved the left ventricular ejection fraction (LVEF), a measurement of left heart function, based on the pooled data from 10 studies (850 patients). Five studies confirmed these benefits, showing a mean decrease in the left ventricle end-diastolic volume — the amount of blood in the left ventricle before the heart contracts.

Levels of NT‐proBNP, a blood-based biomarker for heart failure, were significantly decreased following sacubitril/valsartan treatment.

Despite overall improvements in both right and left heart function, there was no significant relationship between the right heart and left heart function measurements, except for sPAP (pulmonary blood pressure) and left ventricular end-diastolic volume after removing an outlying data point.

Statistical analysis revealed that sample size may have contributed to the variability of TAPSE data, and mean age, heart failure cause, and the sample size also were possible sources of variability in LVEF measures.

Finally, most included studies had a moderate risk of bias due to the lack of control groups as a comparison. Higher bias risk was seen in four studies because they were retrospective, which examined data from past measurements, and low bias was found in one study.

“This meta‐analysis suggested a new therapeutic role for S/V [sacubitril/valsartan], and verified that S/V could improve RV [right ventricle] function and PH in HFrEF,” the scientists wrote.

“Multicenter and randomized controlled trials on large cohorts [groups] are needed to better elucidate the efficacy and safety of S/V on the RV system in patients with HFrEF and determine whether the improvement in RV function is exclusively mediated by improvement in left heart function,” they added.