Drawing Boundaries around PARADISE

This editorial examines the outcomes and clinical implications of the PARADISE-MI trial, which assessed sacubitril–valsartan versus ramipril after acute myocardial infarction. It discusses the neurohormonal mechanisms involved in post-MI heart failure, including the interplay of the renin-angiotensin-aldosterone system and the natriuretic peptide system. While sacubitril–valsartan showed potential for benefit, it did not significantly outperform ramipril in reducing death or incident heart failure in PARADISE-MI. The piece critiques the trial’s statistical outcomes and event rates, cautions against routine initiation of sacubitril–valsartan during hospitalization, and proposes reserving it for outpatient use in high-risk individuals with persistent left ventricular dysfunction. The authors also contrast results from related studies (e.g., PARADIGM-HF, PARAGON-HF, LIFE) and highlight the risks of hypotension and treatment discontinuation. Ultimately, the editorial calls for prudent boundary-setting in expanding indications for angiotensin receptor–neprilysin inhibitors.

This editorial examines the outcomes and clinical implications of the PARADISE-MI trial, which assessed sacubitril–valsartan versus ramipril after acute myocardial infarction. It discusses the neurohormonal mechanisms involved in post-MI heart failure, including the interplay of the renin-angiotensin-aldosterone system and the natriuretic peptide system. While sacubitril–valsartan showed potential for benefit, it did not significantly outperform ramipril in reducing death or incident heart failure in PARADISE-MI. The piece critiques the trial’s statistical outcomes and event rates, cautions against routine initiation of sacubitril–valsartan during hospitalization, and proposes reserving it for outpatient use in high-risk individuals with persistent left ventricular dysfunction. The authors also contrast results from related studies (e.g., PARADIGM-HF, PARAGON-HF, LIFE) and highlight the risks of hypotension and treatment discontinuation. Ultimately, the editorial calls for prudent boundary-setting in expanding indications for angiotensin receptor–neprilysin inhibitors.