Article Impact Level: HIGH Data Quality: STRONG Summary of European Journal of Heart Failure, 23(6), 1040–1048. https://doi.org/10.1002/ejhf.2191 Dr. Karola Jering et al
Points
- The medication used in heart failure including ACEi and ARBs have many adverse effects and less effective clinical outcomes.
- ARNI (Sacubitril/Valsartan) are more effective in treatment of heart failure and following AMI.
- PARADISE-MI is an active comparator-controlled, event-driven trial aimed to investigate if sacubitril/valsartan gives incremental clinical value and a satisfactory safety profile in a contemporarily treated AMI group with enhanced risk.
Summary
Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are drugs of renin angiotensin system (RAS) that are mostly used in heart failure following acute myocardial infarction(AMI). These RAS inhibitors resulted in more adverse effects with further no effective clinical outcomes. These findings have been reflected in the development of international guidelines as well as quality monitoring measures by major medical societies, which suggest the use of either an ACEi or an ARB, but not both, as a component of comprehensive medical therapy for AMI.
Sacubitril/valsartan is a first-in-class angiotensin receptor–neprilysin inhibitor (ARNI). Sacubitril/valsartan blocks the angiotensin II type 1 receptor through valsartan and inhibits the breakdown of vasoactive peptides by neprilysin, including physiologically active natriuretic peptides. Sacubitril/valsartan reduced cardiovascular death, heart failure hospitalisation, and all-cause mortality in patients with lower ejection fraction. Events after Myocardial Infarction (PARADISE-MI) was designed to determine whether sacubitril/valsartan (ARNI) would be superior to ramipril (ACEi) in reducing the composite endpoint of cardiovascular death, heart failure hospitalisation, or outpatient development of heart failure. Ramipril was the drug that was being compared.
PARADISE-MI assigned patients within 0.5–7 days of incident AMI to sacubitril/valsartan or Ramipril. Transient pulmonary congestion and left ventricular ejection fraction (LVEF) 40% and at least one additional risk factor for HF or death (age 70, eGFR 60 mL/min/1.73 m2, diabetes, prior myocardial infarction, atrial fibrillation, LVEF 30%, Killip class III, ST-elevation myocardial infarction without reperfusion) were required for inclusion. PARADISE-MI targeted 708 endpoints (cardiovascular death, HF hospitalization or outpatient development of HF). 5669 patients were randomized 4.3 1.8 days after index AMI. 24% of the 64-year-olds were women. Most (76%) had ST-elevation myocardial infarction; 88% had acute PCI and 6% had thrombolysis. 58% of LVEF was Killip class II.
Sacubitril/valsartan reduces death and heart failure hospitalizations in patients with symptomatic heart failure and reduced ejection fraction. Sacubitril/valsartan reduced heart failure hospitalizations in patients with maintained ejection fraction. The FDA recently increased the use of sacubitril/valsartan to lower the risk of cardiovascular death and hospitalization for heart failure in adults with chronic heart failure. Patients with poor LVEF benefit most. To determine if sacubitril/valsartan avoids heart failure and lowers cardiovascular mortality in AMI patients, a prospective randomized clinical trial PARADISE-MI was designed.
PARADISE-MI is an active comparator-controlled, event-driven trial that was designed to determine whether sacubitril/valsartan offers incremental clinical value and has a satisfactory safety profile when compared to a proven ACEi in a contemporarily treated AMI population with features of augmented risk. The purpose of this trial was to determine whether sacubitril/valsartan offers incremental clinical value and has a satisfactory safety profile. PARADISE-MI is a one-of-a-kind test of the safety and effectiveness of sacubitril/valsartan for the prevention rather than the treatment of symptomatic heart failure. Patients who had a history of heart failure were not allowed to participate in the study, and treatment was started during the AMI event rather than after a run-in period.
Link to the article: https://onlinelibrary.wiley.com/doi/full/10.1002/ejhf.2191
References Jering, K. S., Claggett, B., Pfeffer, M. A., Granger, C., Køber, L., Lewis, E. F., Maggioni, A. P., Mann, D., McMurray, J. J. V., Rouleau, J., Solomon, S. D., Steg, P. G., Meer, P., Wernsing, M., Carter, K., Guo, W., Zhou, Y., Lefkowitz, M., Gong, J., … Braunwald, E. (2021). Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (Paradise‐mi): Design and baseline characteristics. European Journal of Heart Failure, 23(6), 1040–1048. https://doi.org/10.1002/ejhf.2191
