Anthracycline-induced cardiotoxicity: A multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The International CardioOncology Society-one trial

ICOS-ONE Study Investigators, Daniela Cardinale, Fabio Ciceri, Roberto Latini, Maria Grazia Franzosi, Maria Teresa Sandri, Maurizio Civelli, Gian Franco Cucchi, Elisabetta Menatti, Maurizio Mangiavacchi, Raffaele Cavina, Enrico Barbieri, Stefania Gori, Alessandro Colombo, Giuseppe Curigliano, Michela Salvatici, Antonio Rizzo, Francesco Ghisoni, Alessandra Bianchi, Cristina FalciMichele Aquilina, Andrea Rocca, Anna Monopoli, Carlo Milandri, Giuseppe Rossetti, Marco Bregni, Marco Sicuro, Alessandra Malossi, Daniele Nassiacos, Claudio Verusio, Monica Giordano, Lidia Staszewsky, Simona Barlera, Serge Masson, Carlo M. Cipolla, A. P. Maggioni, M. Tettamanti, C. Pellegrini, G. Scognamiglio, G. Corrado, F. De Rosa, S. Callegari, C. Fodor, R. Mazza, E. Sala, G. Fragasso, A. Farolfi, D. Andreis, A. Banzato, E. Gervasi, B. Barco

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Background: Troponin changes over time have been suggested to allow for an early diagnosis of cardiac injury ensuing cancer chemotherapy; cancer patients with troponin elevation may benefit of therapy with enalapril. It is unknown whether a preventive treatment with enalapril may further increase the benefit. Methods: The International CardioOncology Society-one trial (ICOS-ONE) was a controlled, open-label trial conducted in 21 Italian hospitals. Patients were randomly assigned to two strategies: enalapril in all patients started before chemotherapy (CT; ‘prevention’ arm), and enalapril started only in patients with an increase in troponin during or after CT (‘troponin-triggered’ arm). Troponin was assayed locally in 2596 blood samples, before and after each anthracycline-containing CT cycle and at each study visit; electrocardiogram and echocardiogram were done at baseline, and at 1, 3, 6 and 12-month follow-up. Primary outcome was the incidence of troponin elevation above the threshold. Findings: Of the 273 patients, 88% were women, mean age 51 ± 12 years. The majority (76%) had breast cancer, 3% had a history of hypertension and 4% were diabetic. Epirubicin and doxorubicin were most commonly prescribed, with median cumulative doses of 360 [270–360] and 240 [240–240] mg/m2, respectively. The incidence of troponin elevation was 23% in the prevention and 26% in the troponin-triggered group (p = 0.50). Three patients (1.1%) -two in the prevention, one in the troponin-triggered group-developed cardiotoxicity, defined as 10% point reduction of LV ejection fraction, with values lower than 50%. Interpretation: Low cumulative doses of anthracyclines in adult patients with low cardiovascular risk can raise troponins, without differences between the two strategies of giving enalapril. Considering a benefit of enalapril in the prevention of LV dysfunction, a troponin-triggered strategy may be more convenient.
Original languageEnglish
Pages (from-to)126-137
Number of pages12
JournalEuropean Journal of Cancer
Publication statusPublished - May 1 2018


  • Anthracyclines, Cancer chemotherapy, Cardiotoxicity, Clinical trial, Enalapril, Troponin


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