Paradigm-HF: a Paradigm Shift in Heart Failure Treatment?

Abstract

In the first semester of this year, the U.S. Food and Drug Administration (FDA) approved a new drug for the treatment of heart failure, LCZ696, commercially known as Entresto. This new treatment option was evaluated by the FDA on a priority basis (fast track designation), which allowed a faster release than usual. In Brazil, the drug is being evaluated by the National Health Surveillance Agency (Agencia Nacional de Vigilância Sanitaria- ANVISA), similarly to what occurs in Canada and the European Union countries. The scientific evidence that has supported the approval of the new drug by the FDA was primarily obtained from the results of the PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) randomized clinical trial,1 which proved that LCZ696 was more effective than enalapril in a sample of more than 8,000 patients with systolic heart failure. The enthusiasm for the new drug is due to the fact that this is the first, among several drugs tested over more than 20 years, to demonstrate increased efficacy when compared to traditional treatment with Angiotensin-Converting Enzyme (ACE) inhibitors, beta-blockers and spironolactone. However, in the presence of exaggerated enthusiasm, one must carefully evaluate how much this feeling is proportional to the level of evidence. In a systematic analysis, we can say that the PARADIGM-HF trial has a low risk of bias and random errors when concluding that the LCZ696 is superior to enalapril at a dose of 20 mg daily. As for the size of the benefit, 21 patients need to use LCZ696 rather than enalapril for 27 months to prevent an event (death from cardiovascular causes or hospitalization for heart failure). This effect is qualitatively and quantitatively relevant. But does the PARADIGM-HF, in fact, represent a change in the paradigm of heart failure treatment?