LCZ696: too good to be true?

Extract

This editorial refers to ‘A putative placebo analysis of the effects of LCZ696 on clinical outcomes in heart failure’^†, by J. McMurrayet al., on page 434.

This issue of the European Heart Journal contains a major statement by the PARADIGM-HF Investigators,¹ who present an ‘putative placebo’ analysis for LCZ696, a new medicine that yielded a remarkable reduction in total mortality and heart failure events in patients with significant heart failure with reduced ejection fraction (HF-REF). (NB: I serve as a consultant on Novartis's cardiovascular–metabolic advisory group, and have observed the development of this molecule from its inception through the present trial. This bias should be considered when reading this commentary.)

The previously published PARADIGM-HF Trial² (NCT01035255) compared LCZ696 with enalapril, one of the most commonly used angiotensin-converting enzyme inhibitors (ACE-Is), and reported an impressive reduction in death and heart failure events. However, because PARADIGM-HF used an active comparator, the authors asked a logical question: ‘What would the result have been if LCZ696 were compared with placebo?’