Prognostic Value of Albuminuria and Influence of Spironolactone in Heart Failure With Preserved Ejection Fraction

Senthil Selvaraj, Brian Claggett, Sanjiv J. Shah, Inder Anand, Jean L. Rouleau, Eileen O'Meara, Akshay S. Desai, Eldrin F. Lewis, Bertram Pitt, Nancy K. Sweitzer, James C. Fang, Marc A. Pfeffer, Scott D. Solomon

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BACKGROUND: Albuminuria predicts adverse events in heart failure with preserved ejection fraction. No therapies to date have reduced albuminuria in heart failure with preserved ejection fraction. METHODS AND RESULTS: We analyzed 1175 participants from the Americas from the TOPCAT study (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) with urinary albumin:creatinine ratio (UACR) measurements at baseline. We examined the association of UACR with the primary outcome (cardiovascular death, aborted cardiac arrest, or heart failure hospitalization) and its individual components, all-cause mortality, and several safety end points using multivariable-adjusted Cox regression. We evaluated whether spironolactone reduced albuminuria at the 1-year visit in a subpopulation (N=744). Thirty-five percent had microalbuminuria, 13% had macroalbuminuria, and 80% were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Increasing UACR was associated with male sex, higher systolic blood pressure, diabetes mellitus, and renal dysfunction. Macroalbuminuria (hazard ratio, 1.67; 95% CI, 1.22-2.28) and microalbuminuria (hazard ratio, 1.47; 95% CI, 1.15-1.86) were independently associated with the TOPCAT primary end point (compared with normoalbuminuria). Adjusting for placebo response, spironolactone reduced albuminuria by 39% in all participants at the 1-year visit compared with baseline (geometric mean ratio, 0.61; 95% CI, 0.49-0.77) and by 76% (geometric mean ratio, 0.24; 95% CI, 0.10-0.56) among those with macroalbuminuria. Reducing UACR by 50% was independently associated with a reduction in heart failure hospitalization (hazard ratio, 0.90; P=0.017) and all-cause mortality (hazard ratio, 0.91; P=0.019). The change in UACR was significantly associated with change in systolic blood pressure ( P=0.001). CONCLUSIONS: In TOPCAT, albuminuria was independently associated with worse cardiovascular outcomes. Spironolactone significantly reduced albuminuria compared with placebo. Reducing albuminuria was independently associated with improved outcomes. CLINICAL TRIAL REGISTRATION: URL: . Unique identifier: NCT00094302.

Original languageEnglish (US)
Pages (from-to)e005288
JournalCirculation. Heart failure
Issue number11
StatePublished - Nov 1 2018


  • albuminuria
  • blood pressure
  • diabetes mellitus
  • heart failure
  • kidney
  • spironolactone

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


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