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

Circulation. 2006 Dec 5;114(23):2474-81. doi: 10.1161/CIRCULATIONAHA.106.635144. Epub 2006 Nov 13.


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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Antineoplastic Agents / adverse effects*
  • Cardiomyopathies / blood
  • Cardiomyopathies / chemically induced*
  • Cardiomyopathies / physiopathology
  • Cardiomyopathies / prevention & control*
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Enalapril / therapeutic use*
  • Endpoint Determination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Risk Factors
  • Stroke Volume / drug effects
  • Stroke Volume / physiology
  • Troponin I / blood*
  • Ventricular Dysfunction, Left / drug therapy
  • Ventricular Dysfunction, Left / physiopathology


  • Angiotensin-Converting Enzyme Inhibitors
  • Antineoplastic Agents
  • Troponin I
  • Enalapril