Abstract 4364889: Semiquantitative urine dipstick protein assessments predict clinical outcomes in patients with heart failure and reduced ejection fraction: Insights from the GALACTIC-HF trial

Abstract

Background: Although it is known that increased urinary protein excretion is predictive of both end-stage kidney disease and cardiovascular (CV) outcomes, laboratory quantification of urinary albumin is rarely carried out in CV practice. However, dipstick urine testing is often performed in primary and secondary care, although the results may not be routinely inspected or acted upon. Given the renewed emphasis on CV-metabolic-kidney overlap in medicine, we have examined the prognostic value of semiquantitative urine dipstick protein (DP) assessments in patients with heart failure and reduced ejection fraction (HFrEF). Hypothesis: DP predicts clinical outcomes and enables risk stratification in HFrEF. Methods: GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) was a randomized, double-blind, multicenter, event-driven trial that evaluated the efficacy and safety of the cardiac myosin activator omecamtiv mecarbil (OM) versus placebo in 8,232 patients with HFrEF. The primary outcome was a time-to-first-event analysis of a composite of worsening HF (hospitalization or urgent visit) or CV death. We assessed associations between baseline DP and clinical outcomes. Results: Baseline DP data were available for 7,790 patients, of whom 5,910 (75.9%) had a negative test or trace proteinuria, 995 (12.8%) had 1+, and 885 (11.4%) had ≥2+ proteinuria. Patients with DP ≥2+ were younger, more often were in NYHA class III/IV and had diabetes, had higher systolic blood pressure, and lower eGFR (Figure). Mean LVEF was 27% across all DP groups. The rate of the primary outcome (per 100 person-years) increased significantly with increasing DP: negative/trace (21.8, 95% confidential interval [CI] 20.8–22.7); 1+ (34.8, 31.8–38.0); and ≥2+ (38.1, 34.7–41.9). Similar trends were seen for the components of the primary outcome and all cause mortality (Figure). Although individual hazard ratios were partially attenuated after adjustment for recognized prognostic variables, including NT-proBNP and eGFR, higher DP remained significantly associated with worse outcomes. The treatment effect of OM compared with placebo on clinical outcomes was not modified by DP category. Conclusions: DP is a simple inexpensive test with prognostic value in HFrEF.