Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2017 Apr 27;376(17):1690-1692.
doi: 10.1056/NEJMc1612601.

Spironolactone Metabolites in TOPCAT - New Insights into Regional Variation

Simon de Denus  1 , Eileen O'Meara  1 , Akshay S Desai  2 , Brian Claggett  2 , Eldrin F Lewis  2 , Grégoire Leclair  3 , Martin Jutras  3 , Joël Lavoie  4 , Scott D Solomon  2 , Bertram Pitt  5 , Marc A Pfeffer  2 , Jean L Rouleau  4
Affiliations
Comparative Study

Spironolactone Metabolites in TOPCAT - New Insights into Regional Variation

Simon de Denus et al. N Engl J Med. .
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1. Regional Discrepancies in the Reported Use and Actual Use of Spironolactone among Repository Participants in the TOPCAT Trial
The repository participants included 366 patients in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial (206 patients from the United States or Canada and 160 patients from Russia) who provided consent to participate in the TOPCAT biorepository and had sufficient serum samples available from the 12-month study visit. Panel A shows the percentage of participants who reported at 12 months that they were taking the assigned study drug or placebo, and Panel B shows the percentage of participants assigned to spironolactone who reported taking the drug but did not have detectable canrenone concentrations at the 12-month visit. Panel C shows the median canrenone concentration, according to the spironolactone dose at 12 months reported by the participant, and Panel D shows the median canrenone concentration among the participants with detectable canrenone levels, according to the spironolactone dose at 12 months reported by the participant. The Spearman correlation coefficient represents the correlation between reported spironolactone doses and canrenone concentrations. Panel E shows the increases in serum potassium level from baseline to 12 months among the participants (from both regions) who reported taking spironolactone, according to whether they had detectable or undetectable canrenone concentrations. The between-group comparison was significant (P = 0.02). This difference was significant after adjustment for region (P = 0.04); region was not associated with changes in potassium level (P = 0.87). Panel F shows the changes in serum aldosterone level from baseline to 12 months among the participants (from both regions) who were assigned to spironolactone and reported taking the drug, according to whether they had detectable or undetectable canrenone concentrations. The between-group comparison was significant before and after adjustment for region (P<0.001 for both analyses); region was not associated with changes in aldosterone level (P = 0.53).
See this image and copyright information in PMC

Comment in

References

    1. Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370:1383–92. - PubMed
    1. Pfeffer MA, Claggett B, Assmann SF, et al. Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. Circulation. 2015;131:34–42. - PubMed
    1. Tomaszewski M, White C, Patel P, et al. High rates of non-adherence to antihypertensive treatment revealed by high-performance liquid chromatography-tandem mass spectrometry (HP LC-MS/MS) urine analysis. Heart. 2014;100:855–61. - PMC - PubMed
    1. Reilly RF, Jackson EK. Regulation of renal function and vascular volume. In: Brunton LL, Chabner BA, Knollmann BC, editors. Goodman and Gilman’s the pharmacological basis of therapeutics. 12. New York: McGraw-Hill Education; 2011. pp. 671–720.
    1. Aldactone. New York: Pfizer; Oct, 2014. (package insert) ( http://labeling.pfizer.com/ShowLabeling.aspx?id=520)