title: Notable effects of angiotensin II receptor blocker, valsartan, on acute cardiotoxic changes after standard chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone.
abstract: 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.affiliation: Department of Clinical Hematology and Clinical Diagnostics, Cardiology Division, Graduate School of Medicine, Osaka City University, Osaka, Japan. hirohisa@msic.med.osaka-cu.ac.jp
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Nakamae
authors.forename: Kei
authors.initials: K
authors.lastname: Tsumura
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Terada
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nakane
authors.forename: Mika
authors.initials: M
authors.lastname: Nakamae
authors.forename: Kensuke
authors.initials: K
authors.lastname: Ohta
authors.forename: Takahisa
authors.initials: T
authors.lastname: Yamane
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hino
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009367:Neoplasm Staging; D011241:Prednisone / Q000008:administration & dosage; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D015415:Biomarkers; D013777:Tetrazoles; D020097:Natriuretic Peptide, Brain; D014750:Vincristine; D004317:Doxorubicin; D000068756:Valsartan; D009320:Atrial Natriuretic Factor; D003520:Cyclophosphamide; D014633:Valine; D011241:Prednisone