Causal Analysis of the TOPCAT Trial: Spironolactone for Preserved Cardiac Function Heart Failure
This work provides a refined, causal interpretation of clinical trial data to identify effective subgroups, addressing the problem of inconclusive results in heart failure treatment for clinicians and researchers.
The study applied causal discovery methods to the TOPCAT trial data to analyze the effects of spironolactone on heart failure with preserved cardiac function, revealing significant causal effects for specific subgroups and regional discrepancies, despite the trial's overall inconclusive results.
We describe the results of applying causal discovery methods on the data from a multi-site clinical trial, on the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT). The trial was inconclusive, with no clear benefits consistently shown for the whole cohort. However, there were questions regarding the reliability of the diagnosis and treatment protocol for a geographic subgroup of the cohort. With the inclusion of medical context in the form of domain knowledge, causal discovery is used to demonstrate regional discrepancies and to frame the regional transportability of the results. Furthermore, we show that, globally and especially for some subgroups, the treatment has significant causal effects, thus offering a more refined view of the trial results.