PMID- 23940307
OWN - NLM
STAT- MEDLINE
DCOM- 20131118
LR  - 20221207
IS  - 1941-3297 (Electronic)
IS  - 1941-3289 (Linking)
VI  - 6
IP  - 5
DP  - 2013 Sep 1
TI  - Race influences the safety and efficacy of spironolactone in severe heart 
      failure.
PG  - 970-6
LID - 10.1161/CIRCHEARTFAILURE.113.000530 [doi]
AB  - BACKGROUND: The incidence of hyperkalemia caused by mineralocorticoid receptor 
      antagonists may vary by race, but whether race influences efficacy of 
      mineralocorticoid receptor antagonists in heart failure (HF) is unknown. METHODS 
      AND RESULTS: We assessed hyperkalemia and outcomes in African Americans (AAs; 
      n=120) and non-AAs (n=1543; white 93%) with New York Heart Association (NYHA) 
      class III or IV HF and left ventricular dysfunction who were randomized to 
      spironolactone, titrated to 25 or 50 mg daily or placebo, in the Randomized 
      Aldactone Evaluation Study (RALES). AA participants were significantly younger, 
      less likely to have an ischemic HF pathogenesis, more likely to be NYHA 
      functional class IV, and more likely to have a higher estimated glomerular 
      filtration rate and heart rate, less hypertension, diabetes mellitus, or history 
      of myocardial infarction compared with non-AA participants. Potassium increased 
      with spironolactone in non-AAs (4.29+/-0.5-4.55+/-0.49 mmol/L) but not in AAs 
      (4.32+/-0.54-4.31+/-0.49 mmol/L; race by treatment interaction, P=0.03) during the 
      first month and remained higher throughout the trial. Compared with AAs, non-AAs 
      were more likely to attain maximal spironolactone dose (13.9% versus 5.8%; 
      P=0.04) and had higher rates of hyperkalemia (potassium>5.5 mmol/L; 9.7% versus 
      4.2%; P<0.046), as well as lower rates of hypokalemia (potassium<3.5 mmol/L; 5.6% 
      versus 17.9%; P<0.001). After adjustment for differences in baseline 
      characteristics and achieved study drug dose, spironolactone reduced the combined 
      end point of death or hospitalization for HF in non-AAs (hazard ratio, 0.63; 95% 
      confidence interval, 0.55-0.73) but not in AAs (hazard ratio, 1.07; 95% 
      confidence interval, 0.67-1.71; P value for interaction=0.032). CONCLUSIONS: AAs 
      with HF exhibited less hyperkalemia and more hypokalemia with spironolactone 
      compared with non-AAs and seemed to derive less clinical benefit. These 
      hypothesis-generating findings suggest that safety and efficacy of 
      mineralocorticoid receptor antagonists may differ by race.
FAU - Vardeny, Orly
AU  - Vardeny O
AD  - University of Wisconsin School of Pharmacy, Madison, WI.
FAU - Cavallari, Larisa H
AU  - Cavallari LH
FAU - Claggett, Brian
AU  - Claggett B
FAU - Desai, Akshay S
AU  - Desai AS
FAU - Anand, Inder
AU  - Anand I
FAU - Rossignol, Patrick
AU  - Rossignol P
FAU - Zannad, Faiez
AU  - Zannad F
FAU - Pitt, Bertram
AU  - Pitt B
FAU - Solomon, Scott D
AU  - Solomon SD
CN  - Randomized Aldactone Evaluation Study (RALES) Investigators
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130812
PL  - United States
TA  - Circ Heart Fail
JT  - Circulation. Heart failure
JID - 101479941
RN  - 0 (Biomarkers)
RN  - 0 (Mineralocorticoid Receptor Antagonists)
RN  - 27O7W4T232 (Spironolactone)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Adult
MH  - *Black or African American
MH  - Aged
MH  - Biomarkers/blood
MH  - Chi-Square Distribution
MH  - Double-Blind Method
MH  - Female
MH  - Heart Failure/blood/diagnosis/*drug therapy/*ethnology/mortality
MH  - Humans
MH  - Hyperkalemia/blood/chemically induced/ethnology
MH  - Hypokalemia/blood/chemically induced/ethnology
MH  - Male
MH  - Middle Aged
MH  - Mineralocorticoid Receptor Antagonists/adverse effects/*therapeutic use
MH  - Patient Selection
MH  - Potassium/blood
MH  - Proportional Hazards Models
MH  - Risk Factors
MH  - Severity of Illness Index
MH  - Spironolactone/adverse effects/*therapeutic use
MH  - Time Factors
MH  - Treatment Outcome
MH  - United States
MH  - *White People
OTO - NOTNLM
OT  - heart failure
OT  - pharmacology
OT  - potassium
EDAT- 2013/08/14 06:00
MHDA- 2013/11/19 06:00
CRDT- 2013/08/14 06:00
PHST- 2013/08/14 06:00 [entrez]
PHST- 2013/08/14 06:00 [pubmed]
PHST- 2013/11/19 06:00 [medline]
AID - CIRCHEARTFAILURE.113.000530 [pii]
AID - 10.1161/CIRCHEARTFAILURE.113.000530 [doi]
PST - ppublish
SO  - Circ Heart Fail. 2013 Sep 1;6(5):970-6. doi: 10.1161/CIRCHEARTFAILURE.113.000530. 
      Epub 2013 Aug 12.