Abstract | BACKGROUND: 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: CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00094302.
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Authors | 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 |
Journal | Circulation. Heart failure
(Circ Heart Fail)
Vol. 11
Issue 11
Pg. e005288
(11 2018)
ISSN: 1941-3297 [Electronic] United States |
PMID | 30571191
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Mineralocorticoid Receptor Antagonists
- Spironolactone
- Creatinine
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Topics |
- Aged
- Aged, 80 and over
- Albuminuria
(diagnosis, drug therapy)
- Creatinine
(metabolism)
- Female
- Heart Failure
(drug therapy, physiopathology)
- Humans
- Male
- Middle Aged
- Mineralocorticoid Receptor Antagonists
(therapeutic use)
- Spironolactone
(adverse effects, pharmacology)
- Stroke Volume
(drug effects, physiology)
- Treatment Outcome
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