Treatment with angiotensin-converting-enzyme inhibitor for epirubicin-induced dilated cardiomyopathy.
BACKGROUND
Anthracycline chemotherapy in cancer can cause severe, frequently fatal congestive heart failure (CHF), the first-line treatment for which is diuretics and digoxin. We have studied the use of an angiotensin-converting-enzyme (ACE) inhibitor added as a third agent.


METHODS
In an observational study in hospital and as outpatients, 92 patients with advanced breast cancer were treated with epirubicin at a cumulative dose of 360 to 1000 mg/m2 (median 1000). Of 85 evaluable, nine developed life-threatening CHF at 1.5 to 13 months after ending epirubicin. Left ventricular ejection fraction (LVEF) decreased from normal to 18 to 35%. All received frusemide and digoxin, and then, after transient clinical relief, enalapril or ramipril (initially 1.25 mg orally daily, increasing to 10-15 mg after 4-6 weeks).


RESULTS
Eight of the nine patients deteriorated while on digoxin/diuretic. Within 3 months of starting the ACE inhibitor in these patients, LVEF had increased to normal or near normal. Only one patient died in heart failure. Follow-up ranged from 11 to 42 months (median 26). The ACE inhibitor was well-tolerated, with no first-dose hypotension, except for one patient who discontinued treatment after 6 months because of persistent cough. Two others discontinued treatment with their ACE inhibitor after 22 and 28 months because they felt well. Survival in the nine patients was similar to that of those who did not develop CHF.


CONCLUSIONS
Our experience suggests that treatment of anthracycline-induced CHF with an ACE inhibitor should start soon after clinical improvement on digoxin/diuretic regardless of the severity of symptoms rather than waiting for clinical deterioration.
Jensen
B V
BV
Department of Oncology, Herlev Hospital, University of Copenhagen, Denmark.
Nielsen
S L
SL
Skovsgaard
T
T
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced / Q000188:drug therapy*; D004656:Enalapril / Q000627:therapeutic use*; D015251:Epirubicin / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D017257:Ramipril / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000903:Antibiotics, Antineoplastic; D015251:Epirubicin; D004656:Enalapril; D017257:Ramipril