Patients hospitalized for heart failure (HF) treated with adjustable ultrafiltration had a “non-statistically significant trend” towards a longer time to first HF event after index hospitalization, and fewer and shorter re-hospitalizations for HF or cardiovascular causes at 30 days, when compared to adjustable loop diuretics, according to results of the AVOID-HF trial presented Sept. 27 at the Heart Failure Society of America’s Annual Scientific Meeting, and simultaneously published in JACC: Heart Failure. However, due to the trial’s early termination, additional investigation is warranted.

The AVOID-HF trial was designed as a multi-center, one-to-one randomized study of 810 hospitalized HF patients, but was terminated early by the sponsor. Therefore, only 110 patients with similar baseline characteristics were randomized to adjustable ultrafiltration, and 114 to adjustable loop diuretics.

Results showed that estimated days to first HF event for the adjustable ultrafiltration and adjustable loop diuretics group were 62 and 34, respectively (p=0.106). “However the smaller than planned sample size does not provide enough evidence to conclude that this difference is statistically significant (p=0.106),” the investigators explain.

Further, at 30 days, compared to the adjustable loop diuretics group, the adjustable ultrafiltration group had fewer HF and cardiovascular events. However, “more adjustable ultrafiltration patients experienced an adverse effect of special interest (p=0.018) and a serious study product-related adverse event (p=0.026).” Results also showed that renal function changes were similar and the 90 day mortality was similar.

The investigators conclude that the trial results “should be interpreted with caution as the study was unilaterally and prematurely terminated by the Sponsor. Nevertheless, the results of the AVOID-HF trial suggest that decongestion with ultrafiltration requires careful evaluation of the benefit of reducing HF re-hospitalizations with the risk of ultrafiltration-related adverse events.” They add that their findings “underscore the need for additional investigation of this fluid removal approach.”

In a related editorial comment, Daniel B. Mark, MD, MPH, FACC, and Christopher M. O’Connor, MD, FACC, editor-in-chief of JACC: Heart Failure, debate the ethics surrounding the early termination and note that, “While the outcome in AVOID-HF is very disappointing for those of us who thought the potential of intensive decongestion in acute heart failure deserved testing in an adequately powered trial, the trial does not offer a clear ‘teachable moment’ regarding sponsor ethical misconduct.” 

They add that moving forward, “In our current regulatory environment, with the very high cost of bringing new therapies to market, our best defense against more AVOID-HF cases is to only start trials that are designed efficiently, budgeted adequately, and clearly feasible in terms of enrollment targets. If we can achieve that, we will have done much to ensure that the contribution of patients enrolling in our trials is not wasted.”

Keywords: Heart Failure, Hospitalization, Ultrafiltration, Sodium Potassium Chloride Symporter Inhibitors

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