Does sacubitril/valsartan work in acute myocardial infarction? The PARADISE-AMI study

Abstract

Patients with acute myocardial infarction (AMI) complicated by left ventricular dysfunction have an increased risk of death and heart failure. Numerous clinical studies have demonstrated the ability of ACE inhibitors in optimizing the outcome in this particular clinical setting. In recent years, the sacubitril/valsartan association has drastically improved the prognosis of patients with heart failure with reduced ejection fraction with a significant decrease in mortality from cardiovascular causes and hospitalizations due to acute heart failure. However, it has not yet been fully clarified whether this pharmacological association may play a role in patients with AMI. Pre-clinical studies have suggested the possibility that sacubitril/valsartan can reduce the size of the infarct scar and prevent the onset of ventricular arrhythmias in laboratory animals in which myocardial infarction was induced. On the other hand, small clinical experiences with patients after myocardial infarction have provided conflicting data. The results of the PARADISE-MI study were recently presented, which enrolled 5661 patients with AMI complicated by pulmonary congestion and left ventricular dysfunction randomized to therapy with ramipril or sacubitril/valsartan and followed up for ∼2 years. Although combination therapy was associated with an ∼10% reduction in the risk of death from cardiovascular causes or an episode of heart failure, this was not enough to achieve statistical significance. However, treatment with sacubitril/valsartan was shown to be more effective than ramipril in preventing recurrence of heart failure after the first one.

Therapeutic effects and safety of early use of sacubitril/valsartan after acute myocardial infarction: a systematic review and meta-analysis

“…It not only promotes the activity of natriuretic peptide to expand blood vessels, excrete sodium, and induce diuresis, it also inhibits profibrotic signaling markers to function in cardiac failure. This inhibition helps to protect the kidneys (24). Valsartan is a kind of common anti-high blood pressure drug, which is used as an inhibitor of the angiotensin II receptor.…”

Sacubitril Valsartan Enhances Cardiac Function and Alleviates Myocardial Infarction in Rats through a SUV39H1/SPP1 Axis

“…In the PIONEER-HF trial, early treatment of lcz696 in patients with MI reduced the level of N-terminal pro-B-type natriuretic peptide and alleviated LV systolic dysfunction [ 24 ]. The PARADISE-AMI study also showed that patients with acute MI benefit from the lcz696 treatment [ 25 ], and studies are emerging to analyze the treating effect of lcz696 on MI and heart failure [ 15 , 26 ]. Moreover, several studies reported that the molecular changes are involved in the biofunctions of lcz696.…”

Left Ventricular Remodeling after Myocardial Infarction: From Physiopathology to Treatment

“…The effects of ARNI in patients with acute MI were studied in the PARADISE–MI study, which compared sacubitril/valsartan with ramipril in patients with acute MI and with an LV EF < 40% and/or signs of pulmonary congestion. The results of this study showed that sacubitril/valsartan did not reduce cardiovascular death or first HF hospitalization, compared to ramipril, however, it had a clear benefit in all HF events [ 152 , 153 ]. Moreover, in a recent meta-analysis, Zhang et al showed that sacubitril/valsartan therapy after MI prevents adverse ventricular remodeling, thus improving cardiac function and reducing the rate of adverse cardiovascular events [ 149 ].…”