Protective effects of spironolactone against anthracycline‐induced cardiomyopathy

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.

Myocardial Protection During Cardiotoxic Chemotherapy

“…76 Finally, a study has recently reported the preventive effects of spironolactone on anthracycline-induced myocardial toxicity in patients with breast cancer. 77 Important limitations of all of these studies [67][68][69][70][71][72][73][74][75][76][77][78] include the small number of patients treated, differences in study design, varying malignancies being studied and chemotherapy regimens used, and short follow-up times. In addition, in most studies, the mortality rate was lower than expected, and the reported beneficial effects on the incidence of HF and LVEF decline did not translate to lower mortality ( Table 2).…”

Autonomic dysfunction in early breast cancer: Incidence, clinical importance, and underlying mechanisms

“…110 In a recent study of 83 breast cancer patients, 25mg of spironolactone daily during anthracycline treatment mitigated a decrease in LVEF. 111 Lastly, statins have shown benefit for the prevention of anthracycline-based cardiotoxicity in a small single center study. 112 In the breast cancer literature, continuous statin use has been shown to decrease incident heart failure hospitalization among those receiving anthracyclines.…”

Cardio-oncology in the older adult

“…Small randomized controlled trials have evaluated the utility of using mainstays of heart failure therapy, renin angiotensin inhibitors, aldosterone inhibitors and beta-blockers, as preventive therapy for chemotherapy-related cardiotoxicity (31, 66–71). None of these studies looked solely at older patients, but neither were they excluded.…”

“…In the MANTICORE 101-Breast trial, perindopril and bisoprolol each attenuated trastuzumab-related declines in left ventricular systolic function, but did not prevent concurrent left ventricular remodeling, which was the primary outcome measure (73). In a double-blind, placebo-controlled study of spironolactone given simultaneously with anthracycline therapy, spironolactone had a protective effect in the development of left ventricular systolic dysfunction (71). Despite the favorable evidence presented above, routine prophylactic use of these therapies for cardiotoxicity is limited by the lack of consensus, as noted in two meta-analysis with differing conclusions on the benefits of these preventive strategies (32, 74).…”