Protective effects of spironolactone against anthracycline-induced cardiomyopathy

Eur J Heart Fail. 2015 Jan;17(1):81-9. doi: 10.1002/ejhf.196. Epub 2014 Nov 20.

Abstract

Aims: The protective effect of beta-blockers, ACE inhibitors, and ARBs on anthracycline cardiotoxicity has already been demonstrated, but the effect of aldosterone antagonism, which inhibits the last step of the renin-angiotensin-aldosterone system (RAAS), was questioned. This study sought to investigate whether spironolactone protects the heart against anthracycline-induced cardiotoxicity.

Methods and results: Eighty-three female patients who were diagnosed with breast cancer were included in the study. The study population was randomized into spironolactone and control groups. A dose of 25 mg/day spironolactone was administered to the patients in the spironolactone group. There were 43 patients (mean age 50 ± 11 years) in the spironolactone group and 40 patients (mean age 51 ± 10 years) in the control group. LVEF decreased from 67.0 ± 6.1 to 65.7 ± 7.4 (P = 0.094) in the spironolactone group, and from 67.7 ± 6.3 to 53.6 ± 6.8 in the control group (P < 0.001). When the general linear model was applied, the interaction of LVEF decrease between groups was significantly lower in the spironolactone group than in the control group (P < 0.001). The diastolic functional grade of subjects in the spironolactone group was protected (P = 0.096), whereas it deteriorated in the control group (P < 0.001).

Conclusion: We showed that spironolactone administration used simultaneously with anthracycline group chemotherapeutics protects both myocardial systolic and diastolic functions. Spironolactone can be used to protect against anthracycline-induced cardiotoxicity.

Trial registration: NCT02053974.

Keywords: Anthracycline; Cardiomyopathy; Spironolactone.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anthracyclines / adverse effects*
  • Antibiotics, Antineoplastic / adverse effects*
  • Breast Neoplasms / drug therapy*
  • Cardiomyopathies / chemically induced
  • Cardiomyopathies / diagnostic imaging
  • Cardiomyopathies / prevention & control*
  • Double-Blind Method
  • Doxorubicin / adverse effects
  • Echocardiography
  • Epirubicin / adverse effects
  • Female
  • Humans
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Spironolactone / therapeutic use*
  • Treatment Outcome

Substances

  • Anthracyclines
  • Antibiotics, Antineoplastic
  • Mineralocorticoid Receptor Antagonists
  • Spironolactone
  • Epirubicin
  • Doxorubicin

Associated data

  • ClinicalTrials.gov/NCT02053974