The effect of a change in fluid intake advice on outcomes in chronic heart failure: a prespecified subanalysis of the FRESH-UP study.

BACKGROUND AND AIMS: The Fluid REStriction in Heart failure versus liberal fluid UPtake (FRESH-UP) study (NCT04551729) randomized patients with chronic heart failure (HF) to liberal fluid intake (LFI) vs fluid restriction (FR). Pre-trial fluid management may have impacted trial outcomes.

METHODS

The open-label FRESH-UP study randomized 504 patients with chronic HF to an advice of LFI or FR of 1500 ml/day. Primary outcome was the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) after 3 months adjusted for baseline. Key secondary outcome was thirst distress. Patient-reported fluid intake was assessed at Week 6. Safety outcomes included death and hospitalizations. For this subanalysis, participants were stratified according to pre-trial fluid management (FR or LFI).

RESULTS

Prior to randomization, 269 (53.4%) patients adhered to FR and 235 (46.6%) adhered to LFI. After 3 month follow-up, KCCQ-OSS was significantly different between groups (P = .035): in patients changing from pre-trial FR to LFI, KCCQ-OSS was 74.7 [95% confidence interval (CI) 71.2-78.3] compared to 70.2 (95% CI 66.3-74.2) in those with the reversed scenario. In the latter group, thirst distress increased the most. Patient-reported fluid intake was significantly higher in patients randomized to LFI when compared to FR (P = .019), regardless of pre-trial FR or LFI (1771 and 1757 ml, vs 1486 and 1464 ml, respectively). Safety outcomes did not differ.

CONCLUSIONS

These analyses add understanding to the effects of fluid intake management in chronic HF and expose a signal of potential harm of FR in patients with pre-trial LFI and a potential benefit of LFI in patients with pre-trial FR. These results corroborate with the primary results and support that there is no need to routinely initiate or continue FR in stable patients with chronic HF.