Worsening Renal Function during Management for Chronic Heart Failure with Reduced Ejection Fraction: Results From the Pro-BNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) Study

J Card Fail. 2017 Feb;23(2):121-130. doi: 10.1016/j.cardfail.2016.07.440. Epub 2016 Jul 25.

Abstract

Objectives: To assess prognostic meaning of worsening renal failure (WRF) occurring during management of chronic heart failure (HF) with reduced ejection fraction.

Background: When WRF develops during titration of HF medical therapy, it commonly leads to less aggressive care.

Methods: A total of 151 patients enrolled in a prospective, randomized study of standard of care (SOC) HF therapy versus SOC plus a goal N-terminal pro-B type natriuretic peptide (NT-proBNP) < 1000 pg/mL were examined. Cardiovascular (CV) event (defined as worsening HF, hospitalization for HF, significant ventricular arrhythmia, acute coronary or cerebral ischemia, or CV death) at 1 year relative to WRF (defined as any reduction in estimated glomerular filtration rate) 90 days postenrollment were tabulated.

Results: Those developing WRF by 3 months had an average 14% reduction in estimated glomerular filtration rate. There was no difference in incidence of WRF between study arms (43% in SOC, 57% in NT-proBNP, P = .29). During the first 3 months of therapy titration, incident WRF was associated with numerically fewer CV events at 1 year compared with those without WRF (mean 0.81 vs 1.16 events, P = .21). WRF was associated trend toward fewer CV events in the SOC arm (hazard ratio 0.45, 95% confidence interval 0.16-1.24, P = .12); the NT-proBNP-guided arm had numerically lower CV event rates regardless of WRF. Subjects with NT-proBNP <1000 pg/mL and WRF received higher doses of guideline directed medical therapies, lower doses of loop diuretics, and had significantly lower CV event rates (P < .001).

Conclusions: Modest degrees of WRF are common during aggressive HF with reduced ejection fraction management, but we found no significant association with CV outcomes. HF care guided by NT-proBNP was not associated with more WRF compared with SOC, and led to benefit regardless of final renal function.

Keywords: Heart failure; biomarkers; renal failure.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Analysis of Variance
  • Biomarkers / analysis
  • Chronic Disease
  • Cohort Studies
  • Disease Progression
  • Diuretics / therapeutic use
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Heart Failure / blood*
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Humans
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / analysis*
  • Outpatients / statistics & numerical data
  • Peptide Fragments / analysis*
  • Prospective Studies
  • Renal Insufficiency / physiopathology*
  • Risk Assessment
  • Severity of Illness Index
  • Stroke Volume / physiology*
  • Survival Analysis
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Diuretics
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain