Fibrotic heart

The summer of 2015 saw approval of the first new drug for heart failure in almost two decades. The angiotensin receptorneprilysin inhibitor Entresto (formerly LCZ696, Novartis Pharmaceuticals) was approved for heart failure with reduced ejection fraction (HFrEF) on the basis of the results of the PARADIGM-HF trial published in the September 11, 2014 issue of the New England Journal of Medicine.1 MUSC Health cardiologist Michael R. Zile, M.D., who served on the national steering 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 3 million heart failure cases in the U.S. each year. No agent has been shown to improve morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF), who make up the other half of heart failure cases. In patients with HFrEF, the left ventricle does not fully contract, while in those with HFpEF, the ventricle does not fully relax. The two largest clinical trials to date showed that traditional heart failure therapy with angiotensin receptor blockade (Irbesartan or Candesartan) did not improve heart function in patients with HFpEF. According to Zile, “The biggest unmet need in cardiology today is a treatment for HFpEF.”

That could be changing. Zile is on the national steering committee of the PARAGON-HF trial, 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 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.”

For more information about the trials, read "A New Paradigm for the Treatment of Heart Failure."

 Reference

1 McMurray JJ, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. doi: 10.1056/NEJMoa1409077. Epub 2014 Aug 30.