BACKGROUND: There are three distinct types of doxorubicin-induced cardiotoxicity (acute, chronic, and late-onset). Although previous studies with animal models suggest that angiotensin II plays a key role in the process of the doxorubicin-induced cardiotoxicity, there has been no such observation in humans. This randomized study investigated whether valsartan, a new class of angiotensin II receptor blocker (ARB), can inhibit acute cardiotoxicity after doxorubicin-based chemotherapy. METHODS:Forty consecutive patients with untreated non-Hodgkin lymphoma who were scheduled to undergo standard chemotherapy withcyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) (mean age, 56 yrs; range, 24-70 yrs) were randomized with minimization methods to receive CHOP with or without 80 mg/day of valsartan. Acute cardiotoxicity was comprehensively evaluated with neurohumoral, echocardiographic, and electrocardiographic markers before and on Days 3, 5, and 7 after the initiation of CHOP. RESULTS:CHOP induced transient increases in the left ventricular end-diastolic diameter in an echocardiogram, the QTc interval and QTc dispersion in an electrocardiogram, and in the plasma brain and atrial natriuretic peptides. All these changes returned to nearly normal levels within a week after CHOP (P < 0.001). Notably, valsartan significantly prevented all these changes except for the elevation in atrial natriuretic peptide (P < 0.05). No significant change was observed in blood pressure or heart rate between the valsartan and control groups. CONCLUSIONS: The results indicate that angiotensin II may play an essential role in acute CHOP-induced cardiotoxicity in humans. Future long-term studies are necessary to judge whether ARBs have a potential to prevent the chronic or late-onset types of doxorubicin-induced cardiotoxicity.
RCT Entities:
BACKGROUND: There are three distinct types of doxorubicin-induced cardiotoxicity (acute, chronic, and late-onset). Although previous studies with animal models suggest that angiotensin II plays a key role in the process of the doxorubicin-induced cardiotoxicity, there has been no such observation in humans. This randomized study investigated whether valsartan, a new class of angiotensin II receptor blocker (ARB), can inhibit acute cardiotoxicity after doxorubicin-based chemotherapy. METHODS: Forty consecutive patients with untreated non-Hodgkin lymphoma who were scheduled to undergo standard chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) (mean age, 56 yrs; range, 24-70 yrs) were randomized with minimization methods to receive CHOP with or without 80 mg/day of valsartan. Acute cardiotoxicity was comprehensively evaluated with neurohumoral, echocardiographic, and electrocardiographic markers before and on Days 3, 5, and 7 after the initiation of CHOP. RESULTS:CHOP induced transient increases in the left ventricular end-diastolic diameter in an echocardiogram, the QTc interval and QTc dispersion in an electrocardiogram, and in the plasma brain and atrial natriuretic peptides. All these changes returned to nearly normal levels within a week after CHOP (P < 0.001). Notably, valsartan significantly prevented all these changes except for the elevation in atrial natriuretic peptide (P < 0.05). No significant change was observed in blood pressure or heart rate between the valsartan and control groups. CONCLUSIONS: The results indicate that angiotensin II may play an essential role in acute CHOP-induced cardiotoxicity in humans. Future long-term studies are necessary to judge whether ARBs have a potential to prevent the chronic or late-onset types of doxorubicin-induced cardiotoxicity.
Authors: Frederik J F Broeyer; Susanne Osanto; Jun Suzuki; Felix de Jongh; Henk van Slooten; Bea C Tanis; Tobias Bruning; Jeroen J Bax; Henk J Ritsema van Eck; Marieke L de Kam; Adam F Cohen; Yutaka Mituzhima; Jacobus Burggraaf Journal: Br J Clin Pharmacol Date: 2014-11 Impact factor: 4.335
Authors: Juan Carlos Plana; Maurizio Galderisi; Ana Barac; Michael S Ewer; Bonnie Ky; Marielle Scherrer-Crosbie; Javier Ganame; Igal A Sebag; Deborah A Agler; Luigi P Badano; Jose Banchs; Daniela Cardinale; Joseph Carver; Manuel Cerqueira; Jeanne M DeCara; Thor Edvardsen; Scott D Flamm; Thomas Force; Brian P Griffin; Guy Jerusalem; Jennifer E Liu; Andreia Magalhães; Thomas Marwick; Liza Y Sanchez; Rosa Sicari; Hector R Villarraga; Patrizio Lancellotti Journal: Eur Heart J Cardiovasc Imaging Date: 2014-10 Impact factor: 6.875
Authors: Alessandro Colombo; Maria T Sandri; Michela Salvatici; Carlo M Cipolla; Daniela Cardinale Journal: Curr Treat Options Cardiovasc Med Date: 2014-06