The FIRE AND ICE Trial: What We Know, What We Can Still Learn, and What We Need to Address in the Future

Figures

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  Figure 1. Clinical trial success and failure vs patient burden of atrial fibrillation (AF) recurrence. Clinical trial success is illustrated in the top panel by the absence of AF recurrence events from the time of the index ablation through the end of the study period indicated by the vertical, dashed line. The middle panel demonstrates a patient who reached the clinical trial end point via an isolated AF recurrence, indicated by the single, vertical solid line within the study period. The bottom panel represents a patient who reached the clinical trial end point and subsequently experienced multiple AF recurrence events after the initial recurrence, which is demonstrated by the collection of vertical, solid lines over time. Critically, both patients in the middle and bottom panel initially recurred at the same time point during the clinical trial; therefore, these 2 patients are counted equally in the primary efficacy end point, although the burden of AF that followed the initial recurrence drastically differs between the 2 patients.

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  Figure 2. Survival free from predefined secondary end points, including and excluding events that occurred during the 90‐day blanking period (modified intention‐to‐treat cohort). A, Freedom from cardiovascular rehospitalization with and without a 90‐day blanking period in cryoballoon‐ vs radiofrequency current (RFC)–treated cohorts is presented. Freedom from cardiovascular rehospitalization was significantly higher in the cryoballoon cohort both when events in the blanking period were included in the analysis (log‐rank test, P<0.01) and when they were not used (log‐rank test, P=0.02). B, Freedom from repeat ablation in the cryoballoon vs RFC cohort with and without the blanking period is compared. Freedom from repeat ablation was significantly higher in the cryoballoon cohort when events in the blanking period were included in the analysis (log‐rank test, P=0.03), but the cohorts were no longer statistically different when events in the blanking period were excluded (log‐rank test, P=0.10).

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  Figure 3. Flowchart of patient cohort assignment in the FIRE AND ICE Trial. This figure depicts the total number of patients randomized, the total number of patients in the modified intention‐to‐treat (ITT) cohort, and the patients who composed the as‐treated cohorts used for analyses of subcatheter differences. Cryo indicates cryoballoon; RFC, radiofrequency current.

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  Figure 4. Survival free from a primary safety event by catheter subtype. An across‐group analysis of the as‐treated cohort revealed there was no statistical difference in the risk of a primary safety event across catheter subtypes (log‐rank test, P=0.44). RFC indicates radiofrequency current.

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  Figure 5. Freedom from predefined secondary end points by catheter subtype in the as‐treated cohort. A, Freedom from cardiovascular rehospitalization by catheter subtype is displayed; there was a significant difference between catheter types (log‐rank test, P<0.01). B, The freedom from repeat ablation across catheter subtypes in the as‐treated cohort. There was no difference in the rate of repeat ablation when examined by catheter type (log‐rank test, P=0.12). RFC indicates radiofrequency current.