HomePARADISE MI Trial: Is Sacubitril/valsartan (Entresto) useful in patients with acute MI?
PARADISE MI Trial: Is Sacubitril/valsartan (Entresto) useful in patients with acute MI?
December 21, 2021
The PARADISE MI trial is the first of the 10 new trials visual abstracts that we have added to the app. You can download the JPEG of the visual abstract from below. You can use it any way you like as long as you cite the visualmed app or the website along with the original article.
Use of Sacubitril/valsartan in Acute MI?
Sacubitril, a neprilysin inhibitor, has shown to be beneficial when combined with an ARB in patients with chronic heart failure. A similar hypothesis was generated that it might be useful in patients with acute ischemic HF or patients with acute MI who had reduced EF or clinical heart failure. To prove this hypothesis, the PARADISE MI trial was designed. The recruitment was intense and the authors were able to recruit more than 5,000 patients that suitably powered this prospective superiority trial.
Inclusion criteria included patients with reduced EF after the MI
The included population was diverse and consisted of 24% females. Only those acute MI patients were included whose Left ventricular ejection fraction (LVEF) was ≤40% with or without pulmonary congestion. This is important as neprilysin inhibition has been primarily found to be useful in heart failure patients. Also, recall that the PIONEER-HF trial showed significant improvement of NT-proBNP of patients with acute HF who were put on neprilysin inhibition.
Sacubitril/valsartan failed to show superiority over ACEi Ramipril
The primary outcome of cardiovascular (CV) death, first HF hospitalization, or outpatient HF occurred in 11.9% sacubitril/valsartan patients vs. 13.2% in the ramipril group. (p = 0.17) The findings are significantly different from prior trials. One key difference is the use of Ramipril and acute MI population who had MI within the prior 7 days. In the prior studies, the comparison was made with enalapril such as seen in the PARADIGM-HF trial which was done for chronic heart failure patients.
Incremental benefit and safety in acute MI
The authors of PARADISE-MI argued that there is an incremental benefit of ARNI in this specific patient group but is that enough to compel cardiologists to prescribe this drug? ACEi and ARBs are cheaper and easily accessible and with newer data physicians are leaning more towards prescribing these meds over ARNI especially in the vulnerable population who are unable to afford their meds.