Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition

被引:729
作者
Cardinale, Daniela
Colombo, Alessandro
Sandri, Maria T.
Lamantia, Giuseppina
Colombo, Nicola
Civelli, Maurizio
Martinelli, Giovanni
Veglia, Fabrizio
Fiorentini, Cesare
Cipolla, Carlo M.
机构
[1] European Inst Oncol, Cardiol Unit, I-20141 Milan, Italy
[2] European Inst Oncol, Lab Med Unit, I-20141 Milan, Italy
[3] European Inst Oncol, Hematooncol Div, I-20141 Milan, Italy
[4] Univ Milan, Ctr Cardiol Monzino, Milan, Italy
关键词
angiotensin-converting enzyme inhibitors; cardiotoxicity; chemotherapy; heart failure; left ventricular dysfunction; troponin;
D O I
10.1161/CIRCULATIONAHA.106.635144
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:2474 / 2481
页数:8
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