Post-hoc analysis provides additional perspective to understand effects of ARNI in acute MI
Sacubitril/valsartan versus ramipril for patients with acute myocardial infarction: win-ratio analysis of the PARADISE-MI trial
Presented at the ESC congress 2022 by: Otavio Berwanger, MD, PhD- São Paulo, Brazil
Introduction and methods
In the PARADISE-MI trial, patients with acute MI and LVEF ≤40% and/or pulmonary congestion plus any risk enhancer were randomized to sacubitril/valsartan (n=2830) or ramipril (n=2831), but the primary endpoint (time to first event of CV death, HF hospitalization, or outpatient development of HF—all adjudicated by a clinical event classification (CEC) committee) was not met for the sacubitril/valsartan group.
The aim of the current post-hoc analysis was to provide an additional perspective to understand the effects of sacubitril/valsartan in acute MI patients by considering the following aspects simultaneously: (1) the hierarchy of the endpoints (more serious events are given higher priority and are analyzed first), by using the win-ratio method; and (2) the totality of the evidence (including multiple domains of endpoints), by assessing the contribution of events that were confirmed by the CEC committee and those that were not confirmed (i.e. investigator-reported events). The win ratio was calculated as the total number of wins divided by the total number of losses.
Before presenting the results of this post-hoc analysis, dr. Berwanger emphasized that a methodological analysis such as this is usually conducted to help the investigators better understand the results and design future trials. However, it does not change the primary interpretation and clinical implications of the original trial.
- For the primary composite endpoint, the estimated unmatched win ratio of sacubitril/valsartan versus ramipril was 1.17 (95%CI: 1.03–1.33; P=0.015).
- The contribution to the number of wins was greatest for CV death (36.9%) and HF hospitalization (29.8%).
- CEC committee–confirmed events accounted for approximately 70% of the wins, while the remaining 30% of the wins came from events that were not adjudicated.
Dr. Berwanger believes this analysis has two implications. First, when designing future clinical trials, the hierarchy of the events should be considered. Second, some of the CEC committee definitions should perhaps be reviewed to find definitions that are closer to clinical practice.
-Our reporting is based on the information provided at the ESC Congress-