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

• Published in: Circulation (New York, N.Y.) Vol. 114; no. 23; pp. 2474 - 2481
• Main Authors: Cardinale, Daniela, Colombo, Alessandro, Sandri, Maria T., Lamantia, Giuseppina, Colombo, Nicola, Civelli, Maurizio, Martinelli, Giovanni, Veglia, Fabrizio, Fiorentini, Cesare, Cipolla, Carlo M.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 05.12.2006
• Subjects: Adult; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antineoplastic Agents - adverse effects; Biological and medical sciences; Blood and lymphatic vessels; Blood coagulation. Blood cells; Cardiology. Vascular system; Cardiomyopathies - blood; Cardiomyopathies - chemically induced; Cardiomyopathies - physiopathology; Cardiomyopathies - prevention & control; Disease Progression; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Enalapril - therapeutic use; Endpoint Determination; Female; Fundamental and applied biological sciences. Psychology; Humans; Male; Medical sciences; Middle Aged; Molecular and cellular biology; Pharmacology. Drug treatments; Platelet; Predictive Value of Tests; Prospective Studies; Risk Factors; Stroke Volume - drug effects; Stroke Volume - physiology; Toxicity: blood; Troponin I - blood; Ventricular Dysfunction, Left - drug therapy; Ventricular Dysfunction, Left - physiopathology; Heart; Human; Heart failure; angiotensin-converting enzyme inhibitors; Enzyme; Cardiovascular disease; Heart ventricle; left ventricular dysfunction; Left ventricular failure; Prevention; Peptidases; Chemotherapy; Troponin; cardiotoxicity; Treatment; Peptidyl-dipeptidase A; Heart disease; Risk factor; Hydrolases; Peptidyl-dipeptidases; Circulatory system; Left ventricle performance; High dose; ACE inhibitor
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.106.635144

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.