Sacubitril/Valsartan Decreases NT-proBNP, Increases NYHA Class


The drug showed a 30% decrease in NT-proBNP, a blood marker for HFrEF.

Shreeram Aradhye, MD

Shreeram Aradhye, MD

Results of a new real-world analysis have shown that sacubitril/valsartan (Entresto, Novartis) significantly decreases levels of NT-proBNP and improved the New York Heart Association (NYHA) class in patients with heart failure with reduced ejection fraction (HFrEF).

Presented at the American Heart Association’s Scientific Sessions 2017 in Anaheim, California, the results revealed a 30% average decrease (-503 pg/mg; P <.001) in NT-proBNP, an important blood marker used to diagnose heart failure (HF).

The data also showed a reversal in the trend of patients with a worsening NYHA class, with the number of worsening patients dropping from 121 to 81 over 90 days after switching to sacubitril/valsartan.

“People living with heart failure experience symptoms that severely limit their physical activities and quality of life," Shreeram Aradhye, MD, chief medical officer and global head of medical affairs, Novartis Pharmaceuticals, said in a statement. "We are excited to see the growing body of evidence showing that Entresto has a beneficial effect on the quality of life in heart failure, in addition to reducing cardiovascular death and heart failure hospitalization.”

The study examined 1643 patients in total, with 119 evaluated for NT-proBNP changes and 121 for NYHA class trends. The majority of the patients were taking sacubitril/valsartan at its lowest dose of 24/26 mg twice daily, but 36% of patients from primary care centers and 41% from cardiology practices had a dose upped during follow-up.

By the end of the study, fewer than 11% if patients had received the target dose of 97/103 mg twice daily.

Overall, the results were consistent with other real-world data on the drug. Previous studies done in Canada and France showed positive results as well. The 276-patient study done in Canada showed 45% of patients switched to sacubitril/valsartan after 4 weeks, with hat increasing to 56% after 12 weeks. In the 200-patient study in France, a similar NYHA class improvement was observed.

Additionally, in a post-hoc analysis of the PARADIGM-HF study from earlier in 2017, data showed an improvement in patient quality of life as scored by the Kansas City Cardiomyopathy Questionnaire. In the PARADIGM-HF trial, patients’ ability to perform 7 out of 10 tasks were improved.

"What we've done now is we've looked at the way people feel, the symptoms that they have, the limitations that they have, both in physical and social domains. What we found is that in virtually all of these domains, all of these questions, patients reported improvement in their limitations if they were randomized to sacubitril compared to those who were randomized to enalapril," Scott Solomon, MD, an investigator in the PARADIGM trial, told MD Magazine.

Solomon added that these data are the first in HF to show not just an improvement in morbidity and mortality, but an improvement in symptoms and quality of life. "We think this is very exciting because, in fact, most drugs that we have in heart failure that reduce morbidity and mortality, like ACE inhibitors and ARBs and beta blockers, have not really been shown to improve these measures of physical and social limitation and quality of life," he said.

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