The summer of 2015 saw approval of the first new drug for heart failure (HF) in almost two decades. The angiotensin receptor–neprilysin inhibitor Entresto (Novartis Pharmaceuticals) was approved for HF with reduced ejection fraction (HFrEF) based on the results of the PARADIGM-HF trial (NCT01035255) published in the September 11, 2014 issue of the New England Journal of Medicine. MUSC Health cardiologist Michael R. Zile, M.D., who served on the international executive committee of the PARADIGM-HF trial, predicts that the new therapy “will replace ACEs and ARBs as the cornerstone of standard therapy for patients with HFrEF.”
However, patients with HFrEF account for only about half of the three million heart failure cases in the U.S. each year. The other half are attributable to heart failure with preserved ejection fraction (HFpEF). In patients with HFrEF, the left ventricle does not fully contract, while in those with HFpEF, the ventricle does not fully relax. No agent has been shown to improve morbidity and mortality in patients with HFpEF.
That could be changing. Zile is on the international executive committee of the PARAGON-HF trial (NCT01920711), which will assess the efficacy of Entresto in patients with HFpEF, and MUSC Health is one of the sites enrolling patients into the trial. Results are expected in 2017. “PARAGON-HF will be the largest clinical trial in patients with HFpEF,” says Zile. “We hope that Entresto will form the foundation for novel and effective treatment that reduces symptoms and increases survival in HFpEF.”