Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition.
BACKGROUND
An increase in troponin I soon after high-dose chemotherapy (HDC) is a strong predictor of poor cardiological outcome in cancer patients. This finding has important clinical implications and provides a rationale for the development of prophylactic strategies for preventing cardiotoxicity. Angiotensin-converting enzyme inhibitors slow the progression of left ventricular dysfunction in different clinical settings, but their role in the prevention of cardiotoxicity has never been investigated.


RESULTS
Of the 473 cancer patients evaluated, 114 (72 women; mean age, 45+/-12 years) who showed a troponin I increase soon after HDC were randomized to receive (angiotensin-converting enzyme inhibitor group; 20 mg/d; n=56) or not to receive (control subjects; n=58) enalapril. Treatment was started 1 month after HDC and continued for 1 year. Cardiological evaluation was performed at baseline and at 1, 3, 6, and 12 months after HDC. The primary end point was an absolute decrease >10 percent units in left ventricular ejection fraction, with a decline below the normal limit value. A significant reduction in left ventricular ejection fraction and an increase in end-diastolic and end-systolic volumes were observed only in untreated patients. According to the Kaplan-Meier analysis, the incidence of the primary end point was significantly higher in control subjects than in the angiotensin-converting enzyme inhibitor group (43% versus 0%; P<0.001).


CONCLUSIONS
In high-risk, HDC-treated patients, defined by an increased troponin I value, early treatment with enalapril seems to prevent the development of late cardiotoxicity.
Cardinale
Daniela
D
Cardiology Unit, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy. daniela.cardinale@ieo.it
Colombo
Alessandro
A
Sandri
Maria T
MT
Lamantia
Giuseppina
G
Colombo
Nicola
N
Civelli
Maurizio
M
Martinelli
Giovanni
G
Veglia
Fabrizio
F
Fiorentini
Cesare
C
Cipolla
Carlo M
CM
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D009202:Cardiomyopathies / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000627:therapeutic use*; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D019210:Troponin I / Q000097:blood*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000503:physiopathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000970:Antineoplastic Agents; D019210:Troponin I; D004656:Enalapril