Fragility Index Analysis of Contemporary Temporary Mechanical Circulatory Support Devices in Cardiogenic Shock

Background This study offers a complementary method of analyzing statistical robustness of contemporary mechanical circulatory support (MCS) devices trials using the fragility index (FI). The FI is a metric of the minimum number of subjects whose status would have to change from a non-event to an event in order to convert a statistically significant result of a study to a non-significant result. The intent of this study is to apply FI, and its associated metric, fragility quotient (FQ), as additional statistical tools to interpret MCS trials. Methods Eleven randomized clinical trials of MCS were included in this analysis. The MCS trials spanned the duration of the last 2 decades and included devices ranging from intra-aortic balloon pump, micro-axial flow pumps (Impella 2.5, Impella CP, AbioMed), trans-atrial extracorporeal centrifugal pump (Tandem Heart, Tandem Life), and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). A FI analysis was applied to each clinical trial to assess statistical robustness of the primary trial findings. Additional analyses were performed to assess the FI of 30 day mortality, where applicable, and FI of composite adverse events as specified by each trial. Results Eleven randomized clinical trials using MCS in cardiogenic shock were included in our fragility index analysisDanGer shock was the only trial to demonstrate a statistically significant difference in 180-day mortality, however the FI for this trial was a modest 4, while the FI for composite adverse events in this trial was 17. This is in keeping with a signal for increased adverse events such as limb ischemia and vascular complications seen in several trials. All other clinical trials demonstrated negative FIs with varying degrees of magnitude. Conclusion Herein, we apply the fragility index to randomized clinical trials of MCS in cardiogenic shock to further investigate the statistical robustness of the trial findings. Randomized clinical trials on MCS in cardiogenic shock, whether statistically significant or not, demonstrated lack of robustness as defined by FI and are therefore susceptible to random effects. Hence, we advocate for more randomized controlled studies to avoid overestimating the importance and over-reliance on the results of rare trials with statistically significant outcomes.