American heart journal | 2021
Days Alive Out of Hospital in Heart Failure: Insights from the PARADIGM-HF and CHARM Trials.
Abstract
BACKGROUND\nAn endpoint that has received some attention in recent cardiovascular trials is days alive and out of hospital (DAOH). Percent DAOH is a natural extension of DAOH that adjusts for differences in length of follow-up. This endpoint measure incorporates mortality and morbidity together in a way that has the potential to give more insight regarding treatment effects compared to conventional time-to-event endpoints. Other advantages of this measure include the relative ease of collection and interpretation. However, research on how to analyse this measure is still limited.\n\n\nMETHODS\nWe propose using the one-inflated beta model to analyse percent DAOH. This model is appropriate for highly left-skewed data with a large proportion of boundary values. Data from the PARADIGM-HF and CHARM trials are used to illustrate this method.\n\n\nRESULTS\nStatistically significant differences in percent DAOH were observed for PARADIGM-HF and CHARM in favor of treatment. In PARADIGM-HF, treatment with sacubitril plus valsartan increased DAOH on average by 11 days (95% CI: 1.4 - 20.9 days) and increased percent DAOH by 1.64% at a fixed follow-up length of 1,000 days (95% CI: 0.61% - 2.67%). For the CHARM overall program, the candesartan group has 1.79% more DAOH (95% CI: 0.91% - 2.68%).\n\n\nCONCLUSION\nDAOH, and especially percent DAOH, can enhance our understanding of treatment effects in future cardiovascular trials, and the one-inflated beta model is an appropriate choice for its analysis.