Heart Failure: Spironolactone Affects African Americans Differently

MedicalResearch.com: Orly Vardeny, PharmD, MS
Associate Professor of Pharmacy and Medicine
University of Wisconsin-Madison

MedicalResearch.com What are the main findings of the study?

Answer: We performed a post-hoc analysis of the RALES study to assess rates of hyperkalemia and hypokalemia among African American (AA) and non-AA study participants, and examined clinical outcomes by race. We found that AA had less overall increases in potassium compared to non-AA, and exhibited less hyperkalemia with spironolactone. AA subjects were also found to have higher rates of hypokalemia, even among those randomized to spironolactone. Moreover, AA participants appeared to derive less clinical benefit from spironolactone. While non-AA demonstrated reduced risk for death and the combined endpoint of death or heart failure hospitalizations when randomized to spironolactone, African Americans did not derive benefit, and the risk of these outcomes were not different between spironolactone and placebo among AA.

MedicalResearch.com Were any of the findings unexpected?

Answer: A previous study showed that spironolactone therapy was associated with less hyperkalemia among AA compared to non-AA. However, differences in clinical outcomes by race with mineralocorticoid receptor antagonists (MRAs) from a randomized clinical trial had not been examined. We were surprised to learn that not only were hyperkalemia rates different between groups, clinical efficacy varied by race as well.

MedicalResearch.com What should clinicians and patients take away from your report?

Answer: These are hypothesis generating data and results should be interpreted with caution due to our small sample size of AA participants. However, these findings suggest that AA may not respond as well to MRAs, therefore additional, or alternative therapies may be needed to improve clinical outcomes in AA patients with heart failure.

MedicalResearch.com What recommendations do you have for future research as a result of this study?

Answer: In addition to needing more data looking at the response to spironolactone and MRAs in general in African Americans, an important remaining question is why AA patients might respond differently to spironolactone compared to non-AA, and whether this effect is also seen with other MRAs. Are these differences due to genetic factors or other reasons? Future research is needed to confirm our findings in a larger cohort of AA patients, but also to investigate potential mechanistic rationales underlying the differences observed.

Race Influences the Safety and Efficacy of Spironolactone in Severe Heart Failure

Orly Vardeny, Larisa H. Cavallari,, Brian Claggett, Akshay S. Desai, Inder Anand, Patrick Rossignol, Faiez Zannad, Bertram Pitt, and Scott D. Solomon

Circ Heart Fail. 2013;CIRCHEARTFAILURE.113.000530published online before print August 12 2013, doi:10.1161/CIRCHEARTFAILURE.113.00053

Last Updated on August 18, 2013 by Marie Benz MD FAAD