At the 70th annual American College of Cardiology (ACC) 2021 meeting, results were presented for the PARADISE-MI trial. The results demonstrate that for Novartis to remain competitive in the heart failure (HF) market, Entresto will likely require further long-term studies to determine an effective treatment regimen for a broader niche of the HF population including acute myocardial infarction (AMI) and chronic HF populations, says GlobalData, a leading data and analytics company.

Akash Patel, Pharma Analyst at GlobalData, comments: “PARADISE-MI missed its primary endpoint of a 15% reduction in HF events needed to demonstrate superiority of Entresto over Ramipril in the AMI participant population. However, the data suggest that Entresto has incremental clinical benefit compared to Ramipril.”

The PARADISE-MI trial was a double-blind, active-controlled trial which enrolled 5,699 participants who had had an AMI within the previous seven days. All patients had transient pulmonary congestion and/or left ventricular ejection faction (LVEF) ≤40% and at least one additional risk factor for HF or death from: age ≥70 years, estimated glomerular filtration rate <60mL/min/1.73m2, diabetes, prior MI, atrial fibrillation, LVEF <30, Killip class ≥ III, or ST-elevation myocardial infarction (STEMI) without reperfusion.

Although the trial missed its primary endpoint, an exploratory analysis looking at total events found that the difference between Ramipril (n = 539) and Entresto (n = 452) did reach statistical significance in terms of reduction of events (RR 0.79; 95% CI 0.65-0.97). Similarly, investigator-reported outcomes demonstrated an advantage for Entresto over Ramipril when looking at the primary endpoint (HR 0.85; 95% CI 0.75-0.96), as well as for preventing the development of outpatient HF (HR 0.69; 95% CI 0.54-0.88).

Patel adds: “The PARADISE-MI trial results demonstrate that treatment with Entresto did not result in a significant reduction in the rate of CV death, HF hospitalization, or outpatient HF requiring treatment in the AMI population in comparison to established ACE inhibitor Ramipril and therefore this trial is unlikely to drive confidence and uptake of the therapy from physicians.”