Background: An 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 analyze this measure is still limited.
Methods: We propose using the one-inflated beta model to analyze percent DAOH. This model is appropriate for highly left-skewed data with a large proportion of boundary values. Data from the Prospective Comparison of ARNI [Angiotensin Receptor-Neprilysin Inhibitor] with ACEI [Angiotensin-Converting-Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial (PARADIGM-HF) and Candesartan in Heart Failure Assessment of Reduction in Mortality and morbidity (CHARM) trials are used to illustrate this method.
Results: Statistically 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%).
Conclusion: DAOH, 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.
Published by Elsevier Inc.