Published Online
on November 13, 2006

A more recent version of this article appeared on December 5, 2006

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Submitted on April 21, 2006
Revised on September 15, 2006
Accepted on September 21, 2006

Prevention of High-Dose Chemotherapy-Induced Cardiotoxicity in High-Risk Patients by Angiotensin-Converting Enzyme Inhibition

Daniela Cardinale MD^*, Alessandro Colombo MD, Maria T. Sandri MD, Giuseppina Lamantia MD, Nicola Colombo MD, Maurizio Civelli MD, Giovanni Martinelli MD, Fabrizio Veglia PhD, Cesare Fiorentini MD, and Carlo M. Cipolla MD

From the Cardiology Unit (D.C., A.C., G.L., N.C., M.C., C.M.C.), Laboratory Medicine Unit (M.T.S.), and Haemato-Oncology Division (G.M.), European Institute of Oncology, I.R.C.C.S., and Centro Cardiologico Monzino (F.V., C.F.), I.R.C.C.S., University of Milan, Milan, Italy.

^* To whom correspondence should be addressed. E-mail: daniela.cardinale{at}ieo.it.

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.

Methods and 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.

Key words: angiotensin-converting enzyme inhibitors • cardiotoxicity • chemotherapy • heart failure • left ventricular dysfunction • troponin

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