PARADIGM-HF: New drug outclasses to ACE-I in chronic HF

By David Ramsey, ESC Barcelona, 2014

Day 1 at ESC 2014 kicked off with major news about PARADIGM-HF, the 8400-patient trial of the angiotensin receptor–neprilysin inhibitor LCZ696 (Novartis) that was halted early after patients on LCZ696 vs the comparator ACE inhibitor enalapril proved to be living longer, with fewer HF hospitalizations, and comparable safety.

LCZ696 consists of the angiotensin receptor blocker valsartan bonded to the neprilysin inhibitor sacubitril. The trial enrolled 8,442 patients with NYHA class II, III or IV HF and an ejection fraction ≤40% who were randomly assigned to receive LCZ696 400 mg daily or enalapril 20 mg daily in addition to standard care. The mean age of the patients was 63.8 years, one-fifth were women and 66% were white.

“PARADIGM-HF was designed to stand on its own to provide compelling evidence that would convince physicians to replace the current use of ACE inhibitors and angiotensin receptor blockers with LCZ696,” said Milton Packer, MD, professor and chair of the department of clinical sciences at University of Texas Southwestern Medical Center, Dallas.

The results have been known since April of this year, when Novartis announced that the Prospective Comparison of ARNI with ACE-I to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial had been stopped early after LCZ696 showed clinical superiority and at least comparable safety compared with the ACE inhibitor in an interim analysis.

The PARADIGM-HF results were scheduled to be announced at the ESC 2014 to coincide with its publication in the New England Journal of Medicine.