Prospective Comparison of ARNi with ACE-I to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF): paragon of a study or further investigation paramount?

Abstract

The Prospective Comparison of ARNi with ACE-I to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) study clearly represents a landmark in the history of heart failure (HF) trials. Not since the era of β-blocker HF studies have we had a new class of agent for this condition that not only met its primary efficacy end point but also resulted in a stand-alone mortality benefit compared with conventional therapy, and did so with an acceptable safety profile. What was missing from the PARADIGM-HF main results article,1 however, was the clinical impact of the novel intervention, an angiotensin receptor neprilysin (or neutral endopeptidase) inhibitor (ARNi), over the period of follow-up postrandomization. That gap in our knowledge regarding clinical outcomes of this new agent has now been addressed by the article by Packer et al2 in this issue of Circulation . These new findings are focused entirely on surviving patients, drilling down into their clinical course, resource use, and in particular hospitalization requirements. From the data presented, a clear picture emerges of fewer hospitalizations and less need to intensify therapy (via increased use of pharmacological agents, implantation of devices, or cardiac transplantation) with the ARNi, LCZ-696, in comparison with the angiotensin converting enzyme (ACE) inhibitor, enalapril. In addition to clear data supporting attenuated worsening of clinical status, there was also strong evidence that patients had improved quality of life (as assessed by Kansas City Quality of Life Questionnaire) and overall clinical …